益肾康颗粒对糖尿病肾病大鼠肝肾损伤的影响

Influence of Yishenkang Granules on Liver and Kidney Injury in Diabetic Nephropathy Rats

摘要:

目的: 观察益肾康颗粒对糖尿病肾病大鼠肝、肾损伤的影响. 方法: 雄性Wistar健康大鼠通过行单侧肾切除术和链脲佐菌素诱导的方法建立糖尿病肾病模型,将模型成功的43只大鼠随机分为模型组、阳性组和益肾康颗粒2,5,15 g·kg^-1组,阳性组ig给予5.2 mg·kg^-1氯沙坦,益肾康颗粒各给药组分别按剂量2,5,15 g·kg^-1ig给予益肾康颗粒.另取10只健康大鼠作为正常组,正常组和模型组ig给予蒸馏水,所有组均连续ig 12 周.观察大鼠血液中血糖(GLU)、血尿素氮(BUN)、肌酐(SCr)和肝、肾组织中转移生长因子β₁(TGF-β₁),基质金属蛋白酶-9(MMP-9),金属蛋白酶组织抑制物(TIMP-1)的水平. 结果: 与正常组比较,模型组6,12周末的GLU均显著地升高(P<0.05);与正常组比较,模型组6,12周末的SCr,BUN均显著地升高(P<0.05),对糖尿病肾病大鼠治疗后,与模型组对比,益肾康颗粒5,15 g·kg^-1组6,12周末的SCr,BUN均显著性降低(P<0.05).与正常组比较,模型组肾、肝组织的MMP-9降低,TGF-β₁和TIMP-1升高(P<0.05),给药后,与模型组比较,阳性组、益肾康颗粒2,5,15 g·kg^-1组肾、肝组织的TGF-β₁,MMP-9和TIMP-1均具有显著性差异(P<0.05). 结论: 益肾康颗粒能改善糖尿病肾病大鼠肾功能SCr,BUN的表达和肾、肝组织MMP-9,TGF-β₁和TIMP-1表达水平,在改善肾功能的同时,对糖尿病肾病大鼠肝损伤机理有一定的调节作用.

Abstract:

Objective: To explore the influence on matrix metalloproteinase-9 (MMP-9), transforming growth factor-β₁ (TGF-β₁) and tissue inhibitor of metalloproteinase-1(TIMP-1) liver tissue and nephridial tissue injury in diabetic nephropathy rats by Yishenkang granules. Method: Diabetic nephropathy model was established using unilateral nephrectomy combined with streptozotocin induction. Fourty-three diabetic nephropathy rats were randomly divided into model group, positive group, Yishenkang granules groups (2, 5, 15 g· kg^-1). The rats in positive group were ig given 5.2 mg·kg^-1 losartan. The rats in Yishenkang granules were given 2, 5, 15 g· kg^-1Yishenkang granules, respectively. Another 10 normal rats were assigned to normal group. The rats in normal group and model group were ig given distilled water. All rats were given a 12-week treatment. The blood glucose (GLU), blood urea nitrogen (BUN), creatinine (SCr) and the levels of matrix metalloproteinase-9 (MMP-9), transforming growth factor-β₁ (TGF-β₁) and tissue inhibitor of metalloproteinase-1(TIMP-1) in rat liver tissue and nephridial tissue were determined. Result: Compared with normal group, the GLU in model group was increased at weeks 6 and 12 (P<0.05). Compared with normal group, the SCr and BUN in model group were increased at weeks 6 and 12 (P<0.05), and the SCr and BUN were decreased in Yishenkang granules of 5 g·kg^-1 and 15 g· kg^-1 groups after 6- and 12-week treatment (P<0.05). Compared with normal control group, MMP-9 was significantly decreased, TGF-β₁ and TIMP-1 were significantly increased in model group (P<0.05). Compared with model group, the changes of MMP-9, TGF-β₁ and TIMP-1 in positive control group, Yishenkang granules of 2, 5, 15 g· kg^-1groups had significant difference (P<0.05). Conclusion: Yishenkang granules could regulate the expression levels of MMP-9, TGF-β₁ and TIMP-1 in liver tissue of diabetic nephropathy rats. It has certain adjustable effect on mechanism of liver injury and could improve renal function at the same time.