羟甲基戊二酰辅酶A还原酶抑制剂对糖尿病神经病变的保护作用及机制  

Protective effect of 3-hydroxy-3-methylglutary coenzyme A reductase inhibitor on diabetic peripheral neuropathy and action mechanism

作　　者：陈荔枝 高轩[2] 黄金伟[3] 李茜[2] 

机构地区：[1]唐山市工人医院内科,063000 [2]唐山市工人医院神经内科,063000 [3]唐山工人医院分院内科

出　　处：《中华实验外科杂志》2014年第7期1536-1539,共4页Chinese Journal of Experimental Surgery

摘　　要：目的 探讨羟甲基戊二酰辅酶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。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 mellitus 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 maxi- mum 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.

关 键 词：辛伐他汀 糖尿病 疼痛 RhoA/Rho相关卷曲螺旋形成蛋白激酶通路 一氧化氮 

分 类 号：R587.2[医药卫生—内分泌] R741[医药卫生—内科学]