黄芪注射液联合葛根素注射液对糖尿病肾病KKA~y小鼠78kD-葡萄糖调节蛋白的影响

目的观察黄芪注射液联合葛根素注射液对糖尿病肾病KKAy小鼠78k D-葡萄糖调节蛋白(GRP78)表达的影响,为中医药治疗糖尿病肾病提供实验依据。方法雄性KKAy小鼠饲养至12周龄时随机分为模型组和黄芪注射液联合葛根素注射液治疗组;同龄雄性C57BL/6J小鼠作为正常对照组。观察小鼠日常状态,并于16周龄处死小鼠,取血清检测空腹血糖、尿素、肌酐、甘油三酯、总胆固醇,并取肾脏观察肾组织病理形态学变化,免疫组织化学法检测小鼠肾组织中GRP78的表达。结果模型组小鼠空腹血糖、尿素、肌酐、甘油三酯、总胆固醇较对照组明显升高(P0.01);治疗组小鼠空腹血糖、尿素、肌酐较模型组降低(P0.05或P0.01)。形态学观察可见模型组小鼠肾小管上皮细胞胞浆出现空泡;经治疗后,肾小球、肾小管结构完整,病变不明显。免疫组化显示治疗组GRP78表达较模型组明显减少(P0.01)。结论黄芪注射液联合葛根素注射液可在一定程度上抑制KKAy小鼠肾组织中GRP78表达,减轻内质网应激,保护2型糖尿病KKAy小鼠的肾功能。

Effects of astragalus and puerarin injections on the expression of GRP78 in KKAy mice with diabetic nephropathy

Objective To observe the effects of astragalus and puerarin injections on the expression of 78-kD glucose-regulated protein (GRP78) in KKAy mice with diabetic nephropathy.Methods Male KKAy mice were randomly divided into model group and treatment group, and C57BL/6J mice were used as normal control group.The mice in treatment group were given intraperitoneal astragalus injection and puerarin injection from the 12th week.The mice were sacrificed in the 16th week.The blood serum was collected for detecting the levels of fasting blood glucose, urea, creatinine, triglycerides, and total cholesterol.The kidneys were removed and the renal pathological changes were observed.The expression of GRP78 in the renal tissues was examined using immunohistochemical staining.Results Blood biochemical tests in mice showed that, compared with normal mice, the levels of fasting blood glucose, urea, creatinine, total cholesterol and triglycerides increased significantly in model group (P<0.01). Compared with model group, the levels of fasting blood glucose, urea and the creatinine decreased markedly in treatment group (P<0.05 or P<0.01).Under morphological observation, vacuoles were discovered in the cytoplasm of renal tubular epithelial cells in model group.After treatment, the structure of glomerular and tubular were intact, and there were no apparent pathological changes. Immunohistochemistry showed that the expression of GRP78 protein in treatment group was significantly lower than model group ( P <0.01 ) .Conclusion Astragalus injection and puerarin injection used together can reduce the degree of endoplasmic reticulum stress and protect the function of kidney through inhibiting the expression of GRP78 to certain extent.