糖尿病大鼠血管平滑肌细胞内质网应激因子GRP78和caspase12的表达及阿托伐他汀的干预作用  

Expression of ERS-related GRP78 and caspase12 in vascular smooth muscles of diabetic rats and the intervention effect of atorvastatin

作　　者：王清传[1] 张志敏 于鸿杰[1] 王元标[1] 丁小琼[1] 卫聪颖 WANG Qingchuan;ZHANG Zhimin;YU Hongjie;WANG Yuanbiao;DING Xiaoqiong;WEI Congying(Department of Internal Medicine,Office Hospital of Xinjiang Military Region,Urumchi 830000,China;Department of Cardiology,People＇s Hospital of Xianyang City)

机构地区：[1]新疆军区机关医院内科,乌鲁木齐830000 [2]陕西省咸阳市人民医院心内科

出　　处：《山西医科大学学报》2018年第9期1031-1036,共6页Journal of Shanxi Medical University

基　　金：陕西省科学技术攻关课题(2010K 18-H1-6)

摘　　要：目的观察糖尿病大鼠血管平滑肌细胞内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP78及caspase12表达的变化,及阿托伐他汀干预对其表达的影响。方法 6-8周龄雄性SD大鼠15只被随机分为对照组、糖尿病组和阿托伐他汀组,每组5只。对照组大鼠腹腔注射双蒸水,双蒸水灌胃;糖尿病组大鼠腹腔注射1%链脲佐菌素溶液(60 mg/kg),双蒸水灌胃;阿托伐他汀组大鼠腹腔注射1%链脲佐菌素溶液按(60 mg/kg),阿托伐他汀10 mg/(kg·d)灌胃。实验第8周末,检测大鼠血糖、动脉收缩压(SBP)及心率(HR)、脉搏波传导速度(PWV)和主动脉壁中层厚度;免疫组化及Western Blot检测各组大鼠主动脉血管平滑肌组织中GRP78及caspase12蛋白的表达变化。结果对照组大鼠血糖水平为(3.56±2.52)mmol/L;糖尿病组大鼠血糖水平为(22.85±5.73)mmol/L,显著高于对照组(P<0.01);阿托伐他汀组大鼠血糖水平为(20.32±6.51)mmol/L,与糖尿病组差异没有统计学意义(P>0.05)。与对照组相比,糖尿病组大鼠SBP、PWV及主动脉壁中层厚度均明显增高(P<0.05);与糖尿病组相比,阿托伐他汀组大鼠SBP略有降低(P>0.05),PWV及主动脉壁中层厚度均明显降低(P<0.05)。免疫组化结果显示,对照组大鼠平滑肌细胞GRP78及caspase 12表达呈弱阳性表达;糖尿病组GRP78及caspase12呈强阳性表达,显著高于对照组(P<0.01);阿托伐他汀组GRP78及caspase12则呈阳性表达,明显低于糖尿病组(P<0.05)。Western blot结果显示,与对照组相比,糖尿病组大鼠血管平滑肌组织GRP78及Caspase 12蛋白表达量均显著升高(P<0.01);与糖尿病组相比,阿托伐他汀组大鼠血管平滑肌组织GRP78及caspase 12蛋白表达量均明显降低(P<0.05)。结论糖尿病大鼠血管平滑肌细胞ERS激活,应激因子GRP78及caspase12表达升高,caspase12诱导促凋亡信号途径激活,对血管平滑肌细胞起损害作用,可能是糖尿病血管病变的分子机制之一;阿托伐他汀可下调GRObjective To observe the changes of the expression of endoplasmic reticulum stress-related GRP78 and caspase12 in vascular smooth muscle cells（VSMs） of diabetes rats, and explore the effect of atorvastatin on the expression of GRP78 and caspase12.Methods Fifteen male SD rats were randomly divided into control group, diabetes group and atorvastatin group, with 5 rats in each group. The rats in control group were intraperitoneally injected with double distilled water,and then were gavaged with double distilled water daily. The rats in diabetes group were intraperitoneally injected with 1% streptozotocin（60 mg/kg）,and then were gavaged with double distilled water daily. The rats in atorvastatin group were intraperitoneally injected with 1% streptozotocin（60 mg/kg）,and then were gavaged with atorvastatin（10 mg/kg） daily. After 8-week treatment, blood glucose, SBP, HR, PWV and thickness of middle aortic wall were measured, the expression of GRP78 and caspase12 in rat vascular smooth muscles was examined by immunohistochemistry and Western blot.Results The level of blood glucose was （3.56±2.52）mmol/L in control group, （22.85±5.73）mmol/L in diabetes group, and （20.32±6.51）mmol/L in atorvastatin group. Compared with control group, the level of blood glucose in diabetes group was significantly increased（ P 〈0.01）. Compared with diabetes group, the level of blood glucose in atorvastatin group was slightly decreased（ P 〉0.05）. Compared with control group, SBP, PWV and thickness of middle aortic wall were respectively increased in diabetes group（ P 〈0.05）. Compared with diabetes group, SBP was slightly decreased（ P 〉0.05）, while PWV and thickness of middle aortic wall were significantly decreased in atorvastatin group（ P 〈0.05）. Immunohistochemical results showed that the expression of GRP78 and caspase12 were weak positive in VSMs in control group, strong positive in diabetes group（ P 〈0.01 versus control group）, positive in atorvastatin group（ P 〈0.0

关 键 词：糖尿病 大鼠 血管平滑肌细胞 内质网应激 GRP78 caspase12 阿托伐他汀 

分 类 号：R587.1[医药卫生—内分泌]