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Expression of TRPV1 in peripheral blood in adult chronic visceral hypersensitivety rats induced by neonatal colon irritation

Expression of TRPV1 in peripheral blood in adult chronic vis...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Wei-Ying ZOU~1,Bei YANG~1,Ting CHEN~1,Ming-Di XIONG~1,Lei WU~1,Da-Lei ZHANG~1,Ting ZOU~(1,*),Xin-Yan GAO~2,Ri-Xin CHEN~3 1 Department of Physiology,Medical College of Nanchang University,Nanchang,Nanchang 330006,China 2 Institute of Acupuncture & Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700,China 3 Department of Acupuncture and Rehabilitation,Affiliated Hospital of Jiangxi College of Traditional Chinese Medicine,Nanchang,Nanchang 330006,China

Objective TRPV1 is a nonspecific cation channel of the transient receptor potential channel family and may be upregulated during visceral nociceptive *** expression of TRPV1 of nerve fibres,mucosa and muscular layers in gastro-intestinal tract was increased in visceral *** studies demonstrated that TRPV1 is expressed in peripheral blood cells(PBCs).The aim was to investigate whether TRPV1 expression in PBCs is increased in chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal *** Hypersensitive SD rats were generated by colorectal distension(CRD)during postnatal days 8 to *** sensitivity of the colon to balloon distention in adult was measured by grading their abdominal withdrawal reflex(AWR).The PBCs were obtained by cardiac puncture after *** cells were isolated from PBCs by density gradient ***-PCR was performed to detect the expression of TRPV1 and GAPDH *** signal intensity of each TRPV1 band was normalized by *** ODs in each sample were expressed as a ratio of TRPV1 over GAPDH densitometric *** The AWR score in response to CRD in adult rats with neonatal colorectal irritation was significantly higher than control with distension pressures of 20(Mean±SD,1.069±0.457 vs 0.1667±0.389,P<0.01),40(2.069±0.529 vs 1.25±0.753,P<0.01), 60(3.137±0.639 vs 2.20±0.63,P<0.01)and 80 mmHg(3.827±0.601 vs 3.20±0.632,P<0.05).The expression of TRPV1 mRNA of mononuclear cells of PBCs in the control group was in lower level(Mean±SD,0.148±0.084).The TRPV1 expression in neonatal CRD group was increased in adults(Mean±SD,0.724±0.593,P>0.05).Conclusions The colorectal distension in neonates can result in visceral hypersensitivity to CRD in adult rats compared with *** TRPV1 mRNA is expressed in PBCs and its expression may show up-regulation by neonatal colon *** results suggest that the TRPV1 expression in PBCs may be involved in abd

关键词： TRPV1 visceral hypersensitivity

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Identification of the role of phosphodiesterase in mediating memory:implication in Alzheimer’s disease

Identification of the role of phosphodiesterase in mediating...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Rolf HANSEN Marco CONTI Steven P.WILSON James M.O'DONNELL Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences CenterMorgantownWV26506USA Division of Reproductive Biology Department of Obstetrics & GynecologyUniversity of CaliforniaSan FranciscoCA 94143USA Department of Pharmacology Physiologyand NeuroscienceUniversity of South Carolina School of MedicineColumbiaSC 29208USA

＜正＞Objective Phosphodiseterase（PDE） is a superfamily of enzymes that catalyzes the hydrolysis of intracellular cAMP and/or *** the 11 PDE families（PDE1-11）,PDE4 is the most important family in the control of intracellular cAMP *** has been well established that PDE4 plays an essentia]role in the mediation of ***,it is not known whether PDE4 is involved in memory associated with Alzheimer’s disease（AD）. The objective of this study was to identify the role of PDE4 and its isoforms（PDE4A-D） in AD-related memory. Methods Mice deficient in PDE4A,PDE4B,or PDE4D were microinfused withβ-amyloid peptide 1-42（Aβ42;0.4μg/side） or vehicle into bilateral dorsal hippocampi before memory tests using the object recognition,passive avoidance,and Morris water-maze *** silencing was used to identify the role of PDE4 variants in memory. Expression of phosphorylated CREB（pCREB） in the hippocampus was also examined using Western blotting analysis. Results Mice deficient in PDE4A or PDE4D,but not PDE4B,displayed memory enhancement in one or all of the memory ***4A or PDE4D knockout mice also exhibited reversal of Aβ42-induced memory impairment, which was observed in wild-type mice in the object recognition,passive avoidance,and water-maze ***, microinfusions of lentiviral vectors containing microRNAs（miRNAs） that target long-form PDE4D splice variants mimicked the ability of PDE4D deficiency to enhance memory in normal mice;the miRNAs also reversed Aβ42- induced memory deficits in the radial arm maze test in ***,Aβ42 decreased pCREB levels in the hippocampus of wild-type mice or negative control sequence-treated rats,but not mice deficient in PDE4A or PDE4D nor rats treated with *** These results suggest that both PDE4A and PDE4D,in particular the long-form PDE4D isoforms,play an important role in the mediation of memory associated with Alzheimer’s disease. Targeting PDE4A or PDE4D may be a novel approach to tr

关键词： phosphodiesterase memory Alzheimer’s disease gene knockout gene knockdown PDE4 subtypes CREB miRNAs

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The phosphodiesterase-4 inhibitor rolipram reverses Aβ-induced cognitive impairment and neuroinflammatory and apoptotic responses in rats

The phosphodiesterase-4 inhibitor rolipram reverses Aβ-indu...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Chuang WANG~(1,3),Xue-Mei YANG~2,Ye-Ye ZHUO~1,Heng ZHOU~1,Huan-Bing LIN~1,Yu-Fang CHENG~1,Han-Ting ZHANG~(3,*),Jiang-Ping XU~(1,*) 1 Department of Pharmacology,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515, China 2 Hygiene Detection Center,School of Public Health and Tropical Medicine,Southern Medical University,Guangzhou 510515,China 3 Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology,West Virginia University Health Sciences Center,Morgantown,WV 26506,USA

Objectiveβ-Amyloid(Aβ) peptides play an important role in cognition deficits,neuroinflammation,and apoptosis observed in Alzheimer's disease(AD).Activation of cyclic AMP(cAMP) signaling enhances memory and inhibits inflammatory and apoptotic ***,it is not known whether inhibition of phosphodiesterase-4 (PDE4),a critical controller of intracellular cAMP concentrations,affects AD-associated neuroinflammatory and apoptotic responses and whether these responses contribute to deficits of memory mediated by cAMP signaling. Methods The water-maze and passive avoidance tests were used to test memory in rats infused with aggregated Aβ25-35 into bilateral CA1 subregions in the presence or absence of rolipram,a prototypical PDE4 inhibitor. Levels of inflammatory factors and apoptosis-related proteins were measured in the hippocampus of these rats after behavioral tests and confirmed with Aβ1-42 *** Rats microinfused with Aβ25-35(10μg/side) into CA1 displayed deficits in learning ability and memory,as evidenced by increases in escape latency during acquisition trials and decreases in exploratory activities in the probe trial in the water-maze task and 24-h retention in the passive avoidance *** memory deficits were reversed by rolipram(0.1,0.25,and 0.5 mg/kg/d,i.p.) in a dose-dependent ***,Aβ25-35-treated rats also displayed decreases in expression of phosphorylated cAMP responseelement binding protein(pCREB) and Bcl-2,but increases in expression of NF-κB p65 and Bax in the hippocampus;these effects were also reversed by rolipram in a dose-dependent *** neurochemical results were observed by replacing Aβ25-35 with Aβ1-42,a full-length amyloid peptide that quickly forms toxic *** These results suggest that PDE4 inhibitors such as rolipram may reverse Aβ-induced memory deficits at least in part via the attenuation of neuronal inflammation and apoptosis mediated by cAMP/CREB ***4 could be a ta

关键词： CREB memory,phosphodiesterase-4 rolipram P-amyloid

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Inhibition of experimental myopia by a dopamine agonist:an understanding of different effectiveness between form deprivation and hyperopic defocus in guinea pigs

Inhibition of experimental myopia by a dopamine agonist:an u...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Zhi-Na ZHI Xiang-Tian ZHOU Jia QU Dong FENG Miao-Zhen PAN Ruo-Zhong XIE Run-Xia LU Fan-Jun SHI Xin-Jie MAO Jiang-Fan CHEN Mark D.P.WILLCOX School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China School of Optometry and Vision Science The University of New South Wales Sydney NSW Australia School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical College 270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China State Key Laboratory Cultivation Base and Key Laboratory of Vision Science Ministry of Health China and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry.270 Xueyuan Road Wenzhou Zhejiang 325003 China Department of Neurology Boston University School of Medicine Boston MA 02118USA School of Optometry and Vision Science The University of New South Wales Sydney NSW Australia

Objective The dopamine (DA) system in the retina is critical to normal visual development as lack of retinal DA signalling may contribute to myopic *** involvement of DA in myopic development is complex and may be different between form deprivation and hyperopic *** study aims to explore the possible different roles of DA signaling between the FDM and defocus-induced myopia using guinea *** This study evaluated effects of a non-selective DA receptor agonist, apomorphine (APO) on refractive development in guinea pigs treated with form deprivation or hyperopic defocus (from age of 21 to 32 days).Changes in retinal concentration of DA and its metabolites (DOPAC) were also measured in the 2 animal models in order to assess the level of DA involvement in each of the models (the less the change, the lower the involvement).Results (1) Similar myopic degree was induced in both the deprived and defocused eyes (-4.06 D vs.-3.64 D) at 11 days of the experiment.(2)DA and DOPAC levels were reduced in the deprived eyes but did not change significantly in the defocused eyes compared to the fellow and normal control eyes.(3) A subconjunctival injection of APO (from day 1 to 11) at concentrations from 2.5 ng to 250 ng/eye reduced axial myopia treated by form deprivation in a concentration-dependent manner.(4) By contrast, the effectiveness of APO treatment (at concentration from 2.5 ng up to 25 mg/eye) was significantly lower in inhibition of the defocus-induced myopia and the associated axial *** DA signaling may play a more critical role in form deprivation myopia than in defocus-induced myopia, raising a question whether the mechanisms of DA signaling are different under these two types of experimental myopia.

关键词： myopia dopamine guinea pigs form deprivation defocus

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Rheb1 is required for mTORC1 and myelination in postnatal brain development

Rheb1 is required for mTORC1 and myelination in postnatal br...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Jia ZOU Ling-Xue GAN Mao-Wen LUO Qiao-Na YANG Yi-Yuan CUI Wan-Chun YANG Xiao-Qiang XIA Mi-Na CHEN Xia ZHAO Ying SHEN Po Yu CHEN Liang ZHOU Paul F.WORLEY Bo XIAO Xiao-Xia DU Yi-Fei JI Jia XU Jun-Long TIAN Wan-Xiang JIANG Yi ZOU Shou-Yang YU Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China Department of Neuroscience Zhejiang University Hangzhou 310058 China Department of Neuroscience Johns Hopkins University School of Medicine Baltimore MD 21205 USA The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China Department of Neuroscience Zhejiang University Hangzhou 310058 China The State Key Laboratory of Biotherapy West China Hospital Sichuan University Chengdu 610041 China

mTor kinase is involved in cell growth, proliferation, and *** roles of mTor activators, Rheb1 and Rheb2, have not been established in *** generated mice with conditional genetic deletions of Rheb1 and *** deletion of Rheb1 (Actin-cre) results in embryonic death between E10.5 and E11.5 while mutant mice with germiline deletion of Rheb2 mature to adulthood without obvious physical *** cultured mouse embryonic fibroblasts (MEFs) from individual E10.5 embryos, insulin and amino acids activated mTORC1 signalings are selectively impaired in Rheb1-/-*** examine the roles of Rheb1 in vivo, we generated Rheb1 f/f, Nestincre mice in which Rheb1 was conditionally excised in neural progenitor *** mutants were born at expected Medelian ratios and survived up to 6 weeks after birth, mTORC1 signaling is abolished and mTORC2 signaling is increased in developing brain of Rheb1f/f, ***, in Rheb1 f/f, Nestin-cre mutants, the gross morphology of the brains at early postnatal stages was preserved, whereas the myelin formation in later developmental stages was significantly *** TSC mutants in which mTORC 1 signaling were upregulated were previously reported with hypomyelination phenotype, we generated Rosa26 Rheb1 transgenic mouse which conditionally express Rheb 1 in neural progenitor cells to examine whether increasing Rheb1/mTORC 1 activity promotes myelination, or causes ***1 transgene increases mTORC1 activity and promotes myelin formation in the brain, In addition, the Rheb1 transgene rescues mTORC 1 signaling and hypomyelination in the Rheblf/f, Nesin-cre *** study demonstrates that Rheb1, but not Rheb2, is critical for embryonic survival and mTORC1 *** Rheb1 is essential for myelin development in the brain, and suggests that mTORC1 signaling plays a role in selective cellular adaptations, rather than general cellular viability.

关键词： Rheb1 Rheb2 mTor myelination

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Identification of the role of phosphodiesterase in mediating memory:implication in Alzheimer's disease

Identification of the role of phosphodiesterase in mediating...

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中国神经科学学会第九届全国学术会议暨第五届会员代表大会

作者： Han-Ting ZHANG Steven P.WILSON James M.O'DONNELL Yun-Feng LI Ying HUANG Yu-Fang CHENG Chuang WANG Qiang WU Rolf HANSEN Jiang-Ping XU Marco CONTI Beijing Institute of Pharmacology and Toxicology Beijing 100850 China Department of Pharmacology School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China Division of Reproductive Biology Department of Obstetrics & Gynecology University of California San Francisco CA 94143 USA Department of Pharmacology School of Pharmaceutical Sciences Southern Medical University Guangzhou 510515 China Department of Pharmacology Physiology and Neuroscience University of South Carolina School of Medicine Columbia SC 29208 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA Departments of Behavioral Medicine & Psychiatry and Physiology & Pharmacology West Virginia University Health Sciences Center Morgantown WV26506 USA

Objective Phosphodiseterase (PDE) is a superfamily of enzymes that catalyzes the hydrolysis of intracellular cAMP and/or *** the 11 PDE families (PDE1-11), PDE4 is the most important family in the control of intracellular cAMP *** has been well established that PDE4 plays an essential role in the mediation of ***, it is not known whether PDE4 is involved in memory associated with Alzheimer's disease (AD).The objective of this study was to identify the role of PDE4 and its isoforms (PDE4A-D) in AD-related *** Mice deficient in PDE4A, PDE4B, or PDE4D were microinfused with β-amyloid peptide 1-42 (Aβ42; 0.4 μg/side) or vehicle into bilateral dorsal hippocampi before memory tests using the object recognition, passive avoidance, and Morris water-maze *** silencing was used to identify the role of PDE4 variants in *** ofphosphorylated CREB (pCREB) in the hippocampus was also examined using Western blotting *** Mice deficient in PDE4A or PDE4D, but not PDE4B, displayed memory enhancement in one or all of the memory ***4A or PDE4D knockout mice also exhibited reversal of Aβ42-induced memory impairment, which was observed in wild-type mice in the object recognition, passive avoidance, and water-maze ***, microinfusions of lentiviral vectors containing microRNAs (miRNAs) that target long-form PDE4D splice variants mimicked the ability of PDE4D deficiency to enhance memory in normal mice; the miRNAs also reversed Aβ42-induced memory deficits in the radial arm maze test in ***, Aβ42 decreased pCREB levels in the hippocampus of wild-type mice or negative control sequence-treated rats, but not mice deficient in PDE4A or PDE4D nor rats treated with *** These results suggest that both PDE4A and PDE4D, in particular the long-form PDE4D isoforms, play an important role in the mediation of memory associated with Alzheimer's *** PDE4A or PDE4D may b

关键词： phosphodiesterase memory Alzheimer' s disease gene knockout gene knockdown PDE4 subtypes CREB miRNAs

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CMT2L型的转基因小鼠模型的行为学、电生理学和病理学分析

CMT2L型的转基因小鼠模型的行为学、电生理学和病理学分析

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者：张如旭李小波资晓宏黄顺祥张付峰夏昆潘乾唐北沙中南大学湘雅三医院神经内科中南大学湘雅医院神经内科中南大学医学遗传学国家重点实验室

背景腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是最常见的遗传性周围神经病,具有高度的临床和遗传异质性,临床上以肢体远端肌肉进行性对称性的萎缩、无力、腱反射减弱和感觉减退等为主要特征,发病率约为1/2500。2004年,本研究小... 详细信息

背景腓骨肌萎缩症(Charcot-Marie-Tooth disease,CMT)是最常见的遗传性周围神经病,具有高度的临床和遗传异质性,临床上以肢体远端肌肉进行性对称性的萎缩、无力、腱反射减弱和感觉减退等为主要特征,发病率约为1/2500。2004年,本研究小组成功将一个来自中国湖南和湖北的常染色体显性遗传的CMT2型大家系定位于12q24并命名为CMT2L型(OMIM号608673),2005年通过位置候选克隆发现HSPB8为CMT2L型的致病基因,前期工作中我们应用微纤维注射技术构建HSPB8基因K141N的转基因小鼠模型,已获得4只HSPB8首建鼠,并顺利传代获得F2代pCAGGS-HA-HSPB8小鼠4只,F3代pCAGGS-HA-HSPB8小鼠9只。目的对已构建的pCAGGS-HA-HSPB8小鼠进行行为学、电生理学和病理学分析,以期明确HSPB8转基因小鼠模型能否良好再现CMT2L临床表型和可靠用于HSPB8生物学功能和CMT2L发病机理研究。方法取已基因鉴定的pCAGGS-HA-HSPB8转基因鼠(F2代4只,F3代9只)和正常野生型小鼠(normaltype,NT)(F2代9只,F3代9只),共4组,进行包括足迹实验、固定棒试验、旋转棒试验、痛阈实验的行为学分析;使用BL-420E+生物机能实验系统仪进行电刺激后进行坐骨神经复合肌肉动作电位振幅(CMAP)、潜伏期及运动神经传导速度(MNCV)测定的电生理学分析;坐骨神经半薄切片甲苯胺蓝染色光镜下观察和超薄切片电镜下进行周围神经病理学分析。结果足迹试验中HSPB8转基因鼠存在明显步态异常,提示后肢周围神经受损,固定棒试验中发现HSPB8转基因鼠多数蜷曲不动或行走时后肢在前肢的拖拽下费力前进,表明其运动协调能力差,HSPB8转基因鼠在旋转棒上停留时间明显少于正常小鼠,表明其神经肌肉协调能力较正常小鼠差,足底电击痛阈实验未发现HSPB8转基因鼠周围感觉神经受累。以上行为学分析HSPB8转基因鼠说明后肢周围运动神经受累,感觉神经功能相对保存;电生理学分析结果发现HSPB8转基因鼠近端和远端CMAP波幅较NT小鼠低,运动传到速度无统计学差异,表明周围神经损伤以轴索病变为主;病理学分析结果显示突变小鼠半薄切片显示薄髓纤维和无髓纤维明显增多,可见再生簇,电镜下绝大多数板层结构崩解,板层结构消失,轴索裸露和水肿变性。结论 HSPB8转基因小鼠模型良好再现了CMT2L临床表型,能可靠用于HSPB8生物学功能和CMT2L发病机理研究,这也是国际上首次成功建立的CMT2L转基因小鼠模型和HSPB8过表达转基因小鼠模型。

关键词：腓骨肌萎缩症小分子热休克蛋白 B8转基因小鼠

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Transplantation of Olig2-expressing neural stem cells and adoptive immunotherapy of Myelin basic protein activated T cells promotes remyelination and functional recovery after spinal cord injury

Transplantation of Olig2-expressing neural stem cells and ad...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Jian-Guo HU~(1,2,3),Jian-Sheng ZHOU~3,Yu-Xin ZHANG~3,Bao-Ming ZHAO~1,Shan-Feng MA~3,He-Zuo LV~(1,2,*) 1 Center Laboratory,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China 2 Department of Clinical Laboratory Science,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233004, China 3Anhui Key Laboratory of Tissue Transplantation,Bengbu Medical College,Bengbu 233004,China

Neural stem cell transplantation is a major focus of current research in treatment of spinal cord injury (SCI).However,it is very important to promote the transplanted neural stem cells(NSCs) differentiate into OLs and neurons in lesion *** previous studies have shown that 01ig2-overexpression can promote the differentiation of cultured NSCs into mature ***,it has been reported that myelin basic protein activated T cells(MBP-T) can produce neurotrophic factors,improve the SCI local micro-environment,and be neuroprotective to residual myelin and ***,we suppose that combination of 01ig2-modified NSC transplantation and MBP-T cell adoptive immunotherapy may have complementary roles in the treatment of *** this study,the MBP-T cells,which can express IFN-γ,IL-10,and IL-13 after activation in vitro,were passively immunized to spinal cord injured rats within one day after *** NSCs,which were infected with lentivirus expressing green fluorescent protein(GFP-NSCs) or 01ig2(01ig2-GFP-NSCs),were transplanted into injured spinal cord 9 d after *** fate of transplanted cells was tracked by GFP fluorescence after transplantation in different time *** adoptive immunotherapy,the transferred MBP-T cells(CD4-positive) could be detected in injured spinal cord from 3 d to 4 *** infiltration of the MBP-T cells was correlated with and the differentiation of resident microglia and/or infiltrating blood monocytes toward an "alternatively-activated" anti-inflammatory(M2) macrophage *** 2 to 7 weeks after transplantation,the grafted NSCs could be detected to survive and integrate into the injured spinal *** 2 weeks, the survival of grafted NSCs increased fivefold in MBP-T cell-transferred rats compared with vehicle-treated ones. The engrafted GFP-NSCs mostly differentiated into astrocytes,but not OLs and ***,the percentage of MBP-positive OLs increased 12-fold in 01ig2-GFP-NSC-engrafted rats compared with GFP-NS

关键词： spinal cord injury passive immunization Olig2 neural stem cells transplantation

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Effects of puerarin on burn injury pain mediated by P2X3 receptor

Effects of puerarin on burn injury pain mediated by P2X3 rec...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Chang-Shui XU,Jia-Ri LIN,Shuang-Mei LIU,Shang-Dong LIANG~* Department of Physiology,School of Basic Medical Sciences of Nanchang University,Nanchang 330006,China

Objective Peripheral administration of P2X agonists rapidly causes nocifensive behavior in experimental animals and pain sensation in *** of the nociceptive response to peripheral ATP is mediated by P2X *** shows that Puerarin may have anti-nociceptive response and the role of *** effects of Puerarin on rat burn injury pain mediated by P2X receptor was investigated at the present *** Superficial second degree foot/back burn injury models were ***-Dawley rat were randomly divided into sham paw burn group（SPB）,puerarin-treated paw unburned control group（PPC）,untreated superficial second degree paw burn group（UPB）,puerarin-treated superficial second degree paw burn group（PPB）,blank paw control group（BPC group）,sham back burn group（SBB）,puerarin-treated back unburned control group（PBC）,untreated superficial second degree back burn group（UBB）,puerarin-treated superficial second degree back burn group（PBB） and blank back control group（BBC）.Mechanical withdrawal threshold（MWT）and thermal withdrawal latency （TWL）were measured and the expressions of P2X receptor in dorsal root ganglion from test rats were detected by immunohisto-chemistry,RT-PCR,Western blot and in situ *** MWT and TWL in group UPB and PPB were lower than those in group SPB,PPC and BPC（P<0.01）after burn,and the MWT and TWL in group PPB were increased compared with those in group UPB after burn 48 h and 1 h respectively（P<0.05）.After 96 h,there was no difference in MWT and TWL between group PPB and group SPB（P>0.05）,and there also was no difference in MWT and TWL between PPC and BPC（P>0.05）.The MWT and TWL in group UPB were still decreased,there was difference between group UPB and group SPB（P<0.01）,and there also was difference between PPC and BPC （P<0.01）.At day 3 post burn,the expressions of P2X protein and mRNA in dorsal root ganglion from burn injury model rat in group UPB were increased significantly compared with those in other gro

关键词： P2X3 receptor puerarin burn pain

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皮层下缺血性血管性痴呆疾病机制的初探及肌肽对其作用的研究

皮层下缺血性血管性痴呆疾病机制的初探及肌肽对其作用的研究

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者：马婧张晨晖闫海静王熔融胡薇薇陈忠浙江大学药学院浙江大学医学院药理系浙江大学药学院浙江大学医学院药理系

目的血管性痴呆是目前继老年性痴呆之后排名第二的痴呆疾病。皮层下缺血性血管性痴呆是血管性痴呆最常见的亚型,但发病机制尚不清楚,并且至今尚无非常有效的治疗手段。肌肽是一种在动物体脑内广泛分布的天然二肽化合物,具有多种生物学... 详细信息

目的血管性痴呆是目前继老年性痴呆之后排名第二的痴呆疾病。皮层下缺血性血管性痴呆是血管性痴呆最常见的亚型,但发病机制尚不清楚,并且至今尚无非常有效的治疗手段。肌肽是一种在动物体脑内广泛分布的天然二肽化合物,具有多种生物学作用。肌肽在脑内可代谢为组氨酸并通过组氨酸脱羧酶(HDC)作用生成组胺。本实验采用永久性结扎小鼠单侧颈总动脉的血管性痴呆模型,研究血管性痴呆疾病的发病机制以及肌肽对的保护作用及其机制是否与组胺相关。方法将8周龄的C57小鼠随机分为假手术组、模型组、肌肽和组氨酸组。术前半小时腹腔注射肌肽、组氨酸,假手术组和模型组给予生理盐水,永久性结扎单侧颈总动脉建立血管性痴呆模型后饲养28天,期间隔天给予肌肽、组氨酸或生理盐水。在HDC敲除(HDC-KO)小鼠上同法制作此模型,并同法给予肌肽(200 mg/kg)。采用运动量监测、新事物识别、被动穿梭箱、水迷宫模型检测小鼠行为学指标,应用免疫染色检测小鼠大脑白质纤维密度损伤、星型胶质细胞标记物GFAP和小胶质细胞标记物Iba-1的表达,检测手术后1天和28天脑内ROS含量。结果与假手术组相比,新事物识别模型中,手术组的识别分数显著降低,各个剂量的肌肽均能显著提高术后的识别分数;被动穿梭箱模型中,手术后动物进入暗箱的潜伏期显著缩短,其中肌肽(200 mg/kg)和肌肽(500 mg/kg)组能显著延长潜伏期;水迷宫模型中,手术组学习记忆的获得与再获得能力显著降低,而肌肽(200 mg/kg)和肌肽(500 mg/kg)组均能显著改善动物的学习记忆的能力。同时,肌肽(200 mg/kg)也能显著改善HDC-KO小鼠术后在新事物识别、被动穿梭箱及水迷宫模型中的学习记忆能力,而组氨酸各剂量组在野生型小鼠上对以上指标均无明显作用。另外,此模型导致大脑白质进行性损伤,缺血后28天时大脑白质纤维密度显著疏松;缺血后14天起大脑白质区域星形胶质细胞开始激活持续到28天;同时缺血后大脑白质区域和纹状体区域小胶质细胞持续激活。肌肽能剂量依赖的抑制大脑白质纤维疏松并减少大脑白质区域星形胶质细胞的激活,并且显著抑制大脑白质区域和纹状体区域小胶质细胞的激活,组氨酸各剂量组对纤维疏松和星形胶质细胞的激活没有明显影响。在HDC-KO小鼠上,肌肽对以上指标也有显著改善作用。肌肽还可以抑制缺血后1天脑内ROS的增加。结论本实验证实了单侧颈总动脉结扎所致的皮层下缺血性血管性痴呆会导致认知功能障碍,大脑白质纤维进行性损伤、小胶质细胞的持续性激活和星形胶质细胞在后期的激活。肌肽对于皮层下缺血性血管性痴呆有明显保护作用,其机制可能不是通过转化为组胺,而可能是与抑制胶质细胞的激活和抑制ROS的产生有关。

关键词：肌肽皮层下缺血性血管性痴呆白质纤维胶质细胞

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