Restrictive cardiomyopathy（RCM） is associated with cardiac troponin mutations in human *** have created transgenic mice(cTnI mice) that express human RCM R192H（R193H in mouse sequence）.The phenotype of the RCM ani...
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Restrictive cardiomyopathy（RCM） is associated with cardiac troponin mutations in human *** have created transgenic mice(cTnI mice) that express human RCM R192H（R193H in mouse sequence）.The phenotype of the RCM animal model is characterized by restrictive ventricles, biatrial enlargement and an increased risk of sudden cardiac death（SCD）,which are similar to those observed in RCM patients carrying the same cTnI mutations（Du,et al,2006;2008）.The cellular studies indicate that an alteration in myofibril sensitivity for Ca is a key mechanism that causes diastolic dysfunction in *** this study,we have modified cTnI molecules in the heart by crossing cTnI mice with cTnl-ND transgenic mice,the latter contains 100%N-terminal deleted cTnI in the heat characterized by an accelerated cardiac muscle relaxation and an enhanced ventricular diastolic function. The protein analyses data indicate that wild type cTnI is replaced by cTnI-ND in double transgenic mice while the RCM cTnI R193H levels are very similar in the hearts between cTnI mice and the double transgenic mice（about 25%of the total cTnI）.The mortality rate is significantly reduced in double transgenic mice（10%） compared to that in RCM cTnI mice（30%）.The cardiac function and performance are significantly improved in double transgenic mice measured by *** based studies indicate that the delayed sarcomere relaxation time observed in RCM cTnI myocardial cells is significantly shortened in myocardial cells incorporated with cTnI-ND from double transgenic *** left-shift of Ca-dependent myofibril ATPase activities observed in skinned myofibrils from RCM cTnI mouse hearts is also corrected in myofibrils incorporated with cTnI-ND from double transgenic *** results have demonstrated that Ca desensitization caused by cTnI-ND molecules in myocardial cells can correct diastolic dysfunction and rescue RCM transgenic mice,suggesting that Ca desensitization in myofibrils is a therapeutic optio
Objective Explore the possible mechanisms of berberine on peripheral nerve function and neuropathic pain in diabetes *** Adult male SD rats were randomly divided into 3 groups: normal group,diabetes mellitus group,ber...
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Objective Explore the possible mechanisms of berberine on peripheral nerve function and neuropathic pain in diabetes *** Adult male SD rats were randomly divided into 3 groups: normal group,diabetes mellitus group,berberine(187.5 mg/kg) *** diabetic rat modes were i.p. injected with 1%STZ for two weeks,the rats were treated for 8 weeks respectively with berberine. Mechanism withdraw threshold(MWT),heat pain threshold(HPT),sciatic nerve conduction velocity (NCV),histopathological changes of the spinal cord,nitric oxide(NO) content and nitric oxide synthase(NOS) activity in serum and sciatic nerve were determined respectively by Suitable method. Results The NO content and NOS activity in serum and sciatic nerve of DM group were significantly lower than those of NC group(P<0.05 or P<0.01),but in berberine group,the above changes were reversed,there were significant differences compared with those of the DM group(P<0.05 or P<0.01). Conclusion Berberine diabetes can reduce the symptoms of neuropathic pain in rats,preserve structure and function of peripheral *** mechanisms may be increase NOS activity,promote synthesis and release of NO,inhibit inactivation of NO.<正>Objective Explore the possible mechanisms of berberine on peripheral nerve function and neuropathic pain in diabetes *** Adult male SD rats were randomly divided into 3 groups: normal group,diabetes mellitus group,berberine(187.5 mg/kg) *** diabetic rat modes were i.p. injected with 1%STZ for two weeks,the rats were treated for 8 weeks respectively with berberine. Mechanism withdraw threshold(MWT),heat pain threshold(HPT),sciatic nerve conduction velocity (NCV),histopathological changes of the spinal cord,nitric oxide(NO) content and nitric oxide synthase(NOS) activity in serum and sciatic nerve were determined respectively by Suitable method. Results The NO content and NOS activity in serum and sciatic nerve of DM group were significantly lower than those of NC group(P<0.05
The purposes of this article were to investigate whether blood brain barrier(BBB) permeability is altered after Platelet Activating Factor(PAF) induced injury in vitro and elucidate the preliminary possible mechanisms...
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The purposes of this article were to investigate whether blood brain barrier(BBB) permeability is altered after Platelet Activating Factor(PAF) induced injury in vitro and elucidate the preliminary possible mechanisms of *** method was used to observe cell damage after PAF incubation with rat brain microvessel endothelial cells(RBMECs).Intracellular concentrations of Nimodipine in normal and PAF injured RBMECs were estimated by LC-MS/MS analytical method to estimate BBB permeability. Accumulation of P-glycoprotein(P-gp) substrate rhodamine 123 in normal or PAF injured RBMECs was measured with Poly Immune Analysis System-1420 to evaluate the function of P-gp on RBMECs. Intercellular adhesion molecule-1(ICAM-1) mRNA and protein expression levels in RBMECs were assayed by RT-PCR and flow cytometry *** showed that after RBMECs were incubated with 1μM PAF for 24h,cell survival rate was decreased,and intracellular concentrations of Nimodipine were increased *** 123 accumulation between normal and PAF injured cells has not significant difference,but ICAM-1 mRNA and protein expression were increased remarkably in PAF injured cells,which could be inhibited by PAF *** conclusion,the present study demonstrated that BBB permeability was increased after PAF incubation,and which may be due to ICAM-1 up-regulating but not P-glycoprotein function alteration.<正>The purposes of this article were to investigate whether blood brain barrier(BBB) permeability is altered after Platelet Activating Factor(PAF) induced injury in vitro and elucidate the preliminary possible mechanisms of *** method was used to observe cell damage after PAF incubation with rat brain microvessel endothelial cells(RBMECs).Intracellular concentrations of Nimodipine in normal and PAF injured RBMECs were estimated by LC-MS/MS analytical method to estimate BBB permeability. Accumulation of P-glycoprotein(P-gp) substrate rhodamine 123 in normal or PAF injured RBMECs w
Objective TanshinoneⅡ-A(Tan),a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen),possesses anti-oxidant and anti-inflammatory *** present study investigated whether Tan can reduce and stabilize at...
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Objective TanshinoneⅡ-A(Tan),a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen),possesses anti-oxidant and anti-inflammatory *** present study investigated whether Tan can reduce and stabilize atherosclerotic plaques in Apolipoprotein-E knockout(ApoE KO) mice maintained on a high cholesterol diet(HCD). Methods and Results Six week-old mice challenged with a HCD were randomly assigned to 4 groups:(a) C57BL/6J;(b) ApoE KO;(c) Tan-30(30mg/kg/d);(d) Tan-10(10mg/kg/d). After 16 weeks of intervention,Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and en face ***,immunohistochemical analysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by decreased macrophage infiltration and increased smooth muscle cell and collagen *** also significantly reduced in situ superoxide anion production, aortic expression of NF-KappaB,and matrix metalloproteinase-9(MMP-9).In vitro treatment of murine macrophages with Tan significantly suppressed oxidized LDL induced reactive oxygen species(ROS) production and pro-inflammatory cytokines(IL-6,TNF-a,MCP-1) expression. Conclusions Oral administration of Tan effectively prevents the development of atherosclerotic lesions and enhances plaque stability in ApoE KO *** findings highlights Tan as a potential therapeutic agent to prevent cardiovascular diseases.<正>Objective TanshinoneⅡ-A(Tan),a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen),possesses anti-oxidant and anti-inflammatory *** present study investigated whether Tan can reduce and stabilize atherosclerotic plaques in Apolipoprotein-E knockout(ApoE KO) mice maintained on a high cholesterol diet(HCD). Methods and Results Six week-old mice challenged with a HCD were randomly assigned to 4 groups:(a) C57BL/6J;(b) ApoE KO;(c) Tan-30(30mg/kg/d);(d) Tan-10(10mg/kg/d). After 16 weeks of intervention,Tan treated mice showed decreased a
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