非诺贝特对糖尿病大鼠肾功能改善作用及抗氧化应激机制

Protective Effect and Anti-oxidative Stress Mechanism of Fenofibrate in the Kidney of Diabetic Rats

关键词:  非诺贝特  糖尿病肾病  氧化应激  肾保护

Key words:  fenofibrate  diabetic nephropathy  oxidative stress  renal protection

摘要:

目的 研究非诺贝特对糖尿病大鼠肾功能的改善作用及其机制。方法 大鼠一次性腹腔注射链脲佐菌素65 mg?kg^-1制备糖尿病模型，随机分为对照组、模型组，非诺贝特低、中、高剂量(20，40，80 mg?kg^-1)组，每组10只，每天灌胃给予相应剂量的非诺贝特，于第8周末测尿白蛋白(Alb)、视黄醇结合蛋白(RBP)和肌酐；腹主动脉取血，测定血糖和糖化血红蛋白(HbA1c)。取出肾脏，一部分肾组织用4 ℃生理盐水冲洗后，称重研磨制成匀浆，再离心，取上清液测定MDA、SOD活性、GSH活性、NO含量、NOS活性和Na-K-ATP酶活性。另一部分肾组织光镜下检测组织病理学变化。结果 与对照组相比，模型组Alb和RBP明显升高(P<0.05)，肾组织中NO含量、NOS、GSH和SOD活性明显降低(P<0.05)、MDA含量明显升高，Na-K-ATP酶活性降低(P<0.05)，肾组织病理损伤严重。与模型组相比，非诺贝特80 mg?kg^-1组Alb和RBP明显降低(P<0.05)，肾组织中NO含量、NOS、GSH-Px和SOD活性明显上升、MDA含量明显下降，Na-K-ATP酶活性升高(P<0.05)，肾组织病理损伤减轻。结论 非诺贝特能降低糖尿病大鼠肾脏损伤起保护作用，这可能与提高肾脏抗氧化应激损伤有关。

Abstract:

OBJECTIVE To observe the protective effect of fenofibrate(FF) in the kidney of diabetic rats and mechanism of anti-oxidative stress. METHODS All the rats were randomly divided into normal control group, model group and FF (80, 40, 20 mg?kg^-1) group. Diabetic models were established by a single injection of streptozotocin(STZ). Then model group were given distilled water and FF(80, 40, 20 mg?kg^-1) groups were fed with FF. After 8 weeks, Alb, RBP in urine and blood glucose and HbA1c were detected. The renal tissue was acquired for measuring MDA, SOD, GSH, NO, NOS and Na-K-ATP. Histopathological changes in renal tissues were detected. RESULTS Compared with normal control group, Alb and RBP and renal concentration of MDA of FF 80 mg?kg^-1 group increased significantly(P<0.05), while the activity of SOD, NO, NOS, Na-K-ATP and GSH decreased significantly(P<0.05). Compared with model group, Alb and RBP and renal concentration of MDA of FF 80 mg?kg^-1 group decreased significantly(P<0.05), while the activity of SOD, NO, NOS, Na-K-ATP and GSH increased significantly(P<0.05). Histopathology of rats in model group showed renal tubular injury, basophilic change, atrophy, or cystic expansion, mild interstitial inflammatory infiltration while it showed interstitial inflammatory infiltration in FF 80 mg?kg^-1 group. CONCLUSION FF plays a protctive role on diabetic rats renal damage, which may be related with inhibition of oxidative stress.