EGCG对糖尿病大鼠肾脏的保护作用及机制研究  

Protective effect and mechanism of EGCG on kidney of diabetic rats

作　　者：胡相卡 刘作栋 赵苗鑫 董苏敏 杨鹤 刘晓娟 马悦 代春美 HU Xiangka;LIU Zuodong;ZHAO Miaoxin;DONG Sumin;YANG He;LIU Xiaojuan;MA Yue;DAI Chunmei(Jinzhou Medical University,Jinzhou,Liaoning 121001,China)

机构地区：[1]锦州医科大学,辽宁锦州121001

出　　处：《石河子大学学报（自然科学版）》2022年第2期251-258,共8页Journal of Shihezi University(Natural Science)

基　　金：辽宁省教育厅自然科学基金项目(JYTFW201915)。

摘　　要：目的 研究表没食子儿茶素没食子酸酯((-)-Epigallocatechin gallate, EGCG)对链脲佐菌素(Streptozocin, STZ)诱导的糖尿病大鼠肾脏的保护作用及其作用机制。方法 30只SD雄性大鼠随机分为正常对照组、模型组、EGCG剂量组(10、20、40 mg·kg^(-1)·d^(-1)),后4组大鼠一次性腹腔注射STZ(65 mg·kg^(-1))建立糖尿病大鼠模型。于造模成功后第一天开始,EGCG各给药组大鼠按上述剂量灌胃给药,正常对照组和模型组大鼠均给予三蒸水10 mL·kg^(-1)·d^(-1)。药物治疗后第6周和第12周测量各组大鼠的体重、饮水量和摄食量。12周后,测量大鼠双肾质量,计算肾指数,苏木精-伊红(hematoxylin-eosin, HE)染色观察大鼠肾脏病理变化,全自动生化分析仪检测大鼠24 h尿蛋白及血清中血肌酐(Serum creatinine, Scr)、尿素氮(Blood Urea Nitrogen, BUN)水平,按照试剂盒说明书分别检测大鼠血清中空腹血糖(fasting blood glucose, FBG)、甘油三酯(Triglyceride, TG)、胆固醇(Cholesterol, CHO)、白介素-6(Interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factorα, TNF-α)水平,免疫组化法检测大鼠肾组织中转化生长因子β1(transforming growth factor beta 1,TGF-β1)、细胞间粘附分子-1(intercellular cell adhesion molecule-1,ICAM-1)、血管粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)蛋白的表达。结果 给予糖尿病大鼠EGCG 12周,10、20 mg·kg^(-1)·d^(-1)的EGCG可使其饮水量降低(P<0.01)、肾小管上皮细胞空泡样病变有所改善;40 mg·kg^(-1)·d^(-1)的EGCG可使其体重升高(P<0.01),饮水量、摄食量降低(P<0.01)、肾小管上皮细胞空泡样病变明显得到改善;20、40 mg·kg^(-1)·d^(-1)的EGCG可使其血清中Scr下降(P<0.01);10、20、40 mg·kg^(-1)·d^(-1)的EGCG可使糖尿病大鼠血清中FBG、TG和CHO水平降低(P<0.01),肾重和肾脏指数下降(P<0.01),24 h尿蛋白、血清中BUN、IL-6和TNF-α水平下降(P<0.05),肾组织中TGF-β1、ICAM-1蛋白表达下降(P<0.01)Objective To study the protective effect and mechanism of(-)-Epigallocatechin gallate(EGCG) on kidney of diabetic rats induced by streptozocin(STZ). Methods 30 male SD rats were randomly divided into normal control group, model group, EGCG groups(10, 20, 40 mg·kg^(-1)·d^(-1)). The diabetic rat model was established by intraabdominal injection of STZ(65 mg·kg^(-1)) into the rats in the latter four groups. From the first day after the model was established successfully, the EGCG groups were administered intragastrically according to the above doses, and both the normal control group and the model group were administered intragastrically according to 10 mL·kg^(-1)·d^(-1) steamed water. With medication, the body weight, drinking water and food intake of the rats in each group were measured at the 6 th and 12 th week. After 12 weeks, the quality of the two kidneys was measured and the kidney index was calculated. The pathological changes of kidney were observed by hematoxylin-eosin(HE)staining. The levels of Serum creatinine(Scr)and blood urea nitrogen(BUN) in serum and 24 h urinary protein were measured by automatic biochemical analyzer. The levels of fasting blood glucose(FBG), Triglyceride(TG), Cholesterol(CHO), Interleukin-6(IL-6)and tumor necrosis factor α( TNF-α) in serum were detected by their respective kit instructions(ELISA). The expressions of transforming growth factor beta 1(TGF-β1), intercellular cell adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)proteins in renal tissue were detected by immunohistochemistry. Results After diabetic rats were administered intragastrically for 12 weeks, EGCG of 10 and 20 mg·kg^(-1)·d^(-1) could decrease their water intake(P < 0.01), improve their vacuolar lesion of renal tubular epithelial cells;EGCG of 40 mg·kg^(-1)·d^(-1) could increase their body weight(P < 0.01), decrease their water intake and food intake(P < 0.01),and significantly improve vacuolar lesions of renal tubular epithelial cells;EGCG of 20 and 40 mg·kg^(-1)·d^(-1) co

关 键 词：EGCG 糖尿病肾病 TGF-Β1 促炎因子 粘附因子 

分 类 号：R730[医药卫生—肿瘤]