CAJ | 학술논문

目的探讨泾甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂辛伐他汀对糖尿病神经痛的保护作用及其机制.方法观察腹腔注射辛伐他汀对糖尿病小鼠机械痛阈值的影响以及是否与甲羟戊酸途径有关;RhoA/Rho相关卷曲螺旋形成蛋白激酶(ROCK)通路在糖尿病中的作用以及辛伐他汀的干预作用;辛伐他汀对RhoA/ROCK通路下游一氧化氮合酶(NOS)的干预作用.结果辛伐他汀对糖尿病小鼠产生剂量依赖性的镇痛作用,镇痛率为64.7％,此镇痛作用可以被甲羟戊酸(30 mg/kg)所完全阻断;辛伐他汀可以抑制RhoA/ROCK通路,RhoA蛋白抑制剂C3(10 pg)和ROCK抑制剂Y27632(4μg)对糖尿病小鼠的镇痛率分别为47.1％和43.8％;糖尿病疼痛小鼠内皮型一氧化氮合酶(eNOS)表达降低23.9％,辛伐他汀干预RhoA/ROCK通路,使eNOS表达增加至正常小鼠水平,进一步增加NO含量而产生镇痛作用.结论辛伐他汀通过抑制RhoA/ROCK通路,增加eNOS的表达,增加NO含量,从而产生对糖尿病神经痛的镇痛作用.
목적 탐토경갑기무이선보매A(HMG-CoA)환원매억제제신벌타정대당뇨병신경통적보호작용급기궤제.방법 관찰복강주사신벌타정대당뇨병소서궤계통역치적영향이급시부여갑간무산도경유관;RhoA/Rho상관권곡라선형성단백격매(ROCK)통로재당뇨병중적작용이급신벌타정적간예작용;신벌타정대RhoA/ROCK통로하유일양화담합매(NOS)적간예작용.결과 신벌타정대당뇨병소서산생제량의뢰성적진통작용,진통솔위64.7％,차진통작용가이피갑간무산(30 mg/kg)소완전조단;신벌타정가이억제RhoA/ROCK통로,RhoA단백억제제C3(10 pg)화ROCK억제제Y27632(4μg)대당뇨병소서적진통솔분별위47.1％화43.8％;당뇨병동통소서내피형일양화담합매(eNOS)표체강저23.9％,신벌타정간예RhoA/ROCK통로,사eNOS표체증가지정상소서수평,진일보증가NO함량이산생진통작용.결론 신벌타정통과억제RhoA/ROCK통로,증가eNOS적표체,증가NO함량,종이산생대당뇨병신경통적진통작용.
Objective To determine the protective effects of 3-hydroxy-3-methylglutary coenzyme A (HMG-CoA) inhibitors simvastatin on diabetic neuropathic pain and the action mechanism.Methods The analgesic effect of simvastatin on mechanical allodynia threshold in diabetic mice and its association with the mevalonate pathway were studied.The role of RhoA/Rho associated coiled coil forming protein kinase (ROCK) pathway in diabetic melhtus and the analgesic effect of simvastatin were tested.The regulatory effect of simvastatin on the expression of nitric oxide synthase (NOS) was examined in diabetes allodynia.Results The analgesic effect of simvastatin was dose-dependent in diabetic mice,with the maximum effects of 64.7％,which could be blocked by mevalonate completely.Simvastatin inhibited the RhoA/ROCK pathway,while both the RhoA and ROCK inhibitor C3 (10 pg) or Y27632 (4 μg) produced efficacious analgesic effect with the rate of 47.1％ or 43.8％ respectively.The expression of endothelial NOS (eNOS) was decreased by 23.9％ in diabetic mice as compared with normal controls.Simvastatin,by intervening in the RhoA/ROCK pathway,could increase the eNOS expression to a normal level,and then augment NO content and exhibit analgesic effect.Conclusion Simvastatin inhibits RhoA/ROCK pathway,increases the expression of eNOS,and then increases the content of NO,resulting in analgesic effect on diabetic neuropathic pain.