甘油二酯对2型糖尿病肾病大鼠肾脏保护机制

THE PROTECTIVE EFFECTS OF DIACYLGLYCEROL ON DIABETIC NEPHROPATHY IN TYPE 2 DIABETIC RATS

目的探讨甘油二酯(DAG)对糖尿病肾病SD大鼠肾组织蛋白激酶C(PKC)表达和氧化应激的影响。方法SD雄性大鼠40只,选10只为正常对照组(I)用基础饲料喂养。另30只,采用高脂高糖饲料喂养结合链脲佐菌素(STZ)注射诱导2型糖尿病肾病模型(2型DN)。DN成模20只,均分为甘油三酯组(TAG,II)和甘油二酯两组(DAG,III)分别用TAG、DAG饲料持续喂养8w两组饲料组分(%)除TAG、DAG不同外,其余均相同,为:酪蛋白纤维素粉4,矿物质混合物3.5,维生素混合物1,淀粉61.5。实验第2、4、6、8w分别检测空腹血糖(FBG);实验结束前检测24h尿蛋白(UPRO)、血肌酐(SCR);采用苏木精-伊红(HE)染色和Massion染色观察肾脏的病理变化;采用试剂盒法检测肾皮质丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化酶(GSH)活性;免疫组化法检测肾脏中PKC的表达。结果与II组比较,III组可以显著降低模型大鼠FBG(P<0.05),UPRO排泄率显著减少(P<0.05),MDA含量显著下降(P<0.05),肾组织病理改变减轻,并且肾组织内PKC表达下调(P<0.05)。结论 DAG能改善DN大鼠肾功能,抑制氧化应激反应,下调PKC表达,延缓DN的发生发展;推测DAG保护2型糖尿病大鼠肾脏的机制与其有关。

Objective To investigate the effects of diacylglycerol（DAG） on oxidative stress and expression of protein kinase C（PKC） in the kidney of diabetic nephropathy（DN） rats. Methods Thirty SD male rats were randomly divided into normal group（I）, triglyceride（TAG） group（II）, DAG group（III）. Diabetes was induced by feeding a high fat and sugar diet and then injecting streptozotocin（STZ）. DAG fodder and TAG fodder were given to the DAG group and the TAG group respectively after DN model was successfully established for 8 weeks, while normal group was fed ordinary fodder all the time. Fasting blood glucose（FBG） was detected at weeks 2, 4, 6 and 8w,and 24 h urine protein（UPRO）, serum creatinine（SCR） were detected at week 8; pathomor-phological changes in renal tissue were evaluated by staining with hematoxylin-eosin（HE） and Massion. The content of MDA, the activity of superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px） were examined by related kits. The expression of PKC in renal tissues was detected by immunohistochemisty. Results Compared with the II group, the content of FBG, UPRO and MDA were significantly reduced in the III group（P〈0.05）. Pathomorphological changes were improved and PKC expression in renal tissues was also significantly decreased in the III group as compared with the II group（P〈0.05）. Conclusion DAG can improve renal function of DN rats and inhibit oxidative stress, reduce the expression of PKC and delay the development of DN.