二氢杨梅素对糖尿病肾病大鼠肾纤维化的影响

The Effect of Dihydromyricetin on Renal Fibrosis in Diabetic Nephropathy Rats

目的:探讨二氢杨梅素(DMY)对糖尿病肾病(DN)大鼠的保护作用及其对肾纤维化的影响。方法:采用大剂量(55mg·kg^-1)链脲佐菌素(STZ)腹腔注射建立DN模型,以血糖>16.7mmol·L^-1为建模成功。将大鼠随机分为正常组、模型组和低、中、高剂量DMY组(125、250、500mg·kg^-1)。DMY组采用灌胃给药,模型组采用生理盐水灌胃,持续12周。生化检测各组大鼠24h尿蛋白(24h-Pro)、血尿素氮(BUN)和血肌酐(Scr)的含量。HE染色观察各组大鼠肾脏形态学变化,PAS染色观察各组肾组织基底膜厚度的变化,Masson染色观察各组肾小球硬化和肾间质纤维化程度。Westernblot检测各组大鼠肾组织TGF-β1、Smad2、Smad7表达水平。结果:与正常组比较,DN模型组24h-Pro、BUN、Scr的含量明显升高(P<0.01)。与模型组比较,各剂量DMY组24h-Pro、BUN、Scr的含量下降(P<0.01)。病理结果显示模型组大鼠肾组织可见肾小球体积增大,胶原纤维增生,基底膜增厚。与模型组比较,各剂量DMY组胶原纤维不同程度减少。与正常组比较,模型组大鼠TGF-β1、Smad2蛋白表达水平增加,Smad7蛋白表达水平下降(P<0.05)。DMY干预后,能明显抑制大鼠肾组织中TGF-β1、Smad2蛋白表达上调和Smad7蛋白下调(P<0.05)。结论:DMY能改善DN大鼠肾脏组织纤维化,其机制可能与抑制TGF-β1/Smads通路过度激活有关。

Objective: To investigate the protective effect of Dihydromyricetin (DMY) on diabetic nephropathy (DN) rats and its effect on renal fibrosis. Methods: DN model was established by intraperitoneal injection of streptozotocin with high dose (55mg/kg). The model was successfully established with blood sugar > 16.7mmol/L. Rats were randomly divided into normal group, model group, low, medium and high dose DMY group (125, 250, 500 mg/kg). DMY group was given intragastric administration, while model group was given normal saline intragastricadministration for 12 weeks. The levels of 24-hour urinary protein (24h-Pro), blood urea nitrogen (BUN) and Serum creatinine (Scr) in rats of each group were detected by biochemical method. HE staining was used to observe the morphological changes of kidneys of rats in each group, PAS staining was used to observe the changes of renal basement membrane thickness in each group, Masson staining was used to observe the degree of glomerulosclerosis and renal interstitial fibrosis in each group. The expression levels of TGF-β1, Smad2 and Smad7 in kidney tissues of rats in each group were detected by Western blot. Result: Compared with the normal group, the levels of 24h-Pro, BUN and Scr in DN model group were significantly higher (P<0.01). Compared with model group, the levels of 24h-Pro, BUN and Scr in DMY group decreased (P<0.01). Pathological results showed that glomerular volume increased, collagen fibers proliferated and basement membrane thickened in the model group. Compared with the model group, collagen fibers in DMY group decreased in different degrees. Compared with the normal group, the expression levels of TGF-β1 and Smad2 increased and Smad7 decreased in the model group (P<0.05). DMY could significantly inhibit the up-regulation of TGF-β1, Smad2 and down-regulation of Smad7 in renal tissue of rats (P<0.05). Conclusion: DMY can improve renal fibrosis in rats with DN, and its mechanism may be related to the inhibition of excessive activation of TGF-β1/Smads pathway.