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目的观察桑叶总黄酮对1型糖尿病小鼠肾间质纤维化的防治作用及其可能机制。方法采用腹腔注射链脲佐菌素(STZ)150 mg·kg~(-1)制备糖尿病小鼠模型,造模成功后分为模型组、桑叶总黄酮低(0.25 g·kg~(-1))、中(0.5 g·kg~(-1))、高(1 g·kg~(-1))剂量组各10只,另设正常对照组8只。每日灌胃1次,连续给药12周后,测定各组小鼠空腹血糖(FBG)、血清肌酐(Cr)、尿素氮(BUN)、尿微量白蛋白(m Alb);Masson染色、天狼星红(Sirus red)染色以及IV型胶原蛋白(collagenⅣ)免疫组织化学染色检测小鼠肾皮质中胶原蛋白表达;层黏连蛋白(laminin)染色评估小鼠肾小球及肾小管基底膜的增厚程度。Western blot检测小鼠肾皮质中上皮间质转化(epithelial-mesenchymal transition,EMT)及信号通路PI3K/Akt/mTOR的相关蛋白表达。结果中、高剂量的桑叶总黄酮能够明显降低糖尿病小鼠血糖、血清肌酐、尿素氮及尿微量白蛋白水平,并通过抑制PI3K/Akt/mTOR信号通路的激活,增加上皮型标志物E-cadherin,降低间质型标志物α-SMA的蛋白表达,改善肾脏组织的病理形态变化。结论中、高剂量桑叶总黄酮能减轻1型糖尿病小鼠肾间质纤维化水平,其机制可能与抑制PI3K/Akt/mTOR信号通路的激活有关。
Objective To observe the preventive and therapeutic effects of mulberry leaf flavonoids on renal interstitial fibrosis in type 1 diabetic mice and its possible mechanism. Methods Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ) 150 mg · kg -1, and were divided into model group and model group. The total flavonoids in mulberry leaves were low (0.25 g · kg -1 ), Medium (0.5 g · kg -1) and high (1 g · kg -1) groups respectively, and another 8 normal control group. The rats in each group were given gavage once a day for 12 weeks. The fasting blood glucose (FBG), serum creatinine (Cr), blood urea nitrogen (BUN) and urinary albumin (Alb) Sirus red staining and collagen Ⅳ immunohistochemical staining were used to detect the expression of collagen in mouse renal cortex. The laminin staining was used to evaluate the glomerular and tubular cell thickening degree. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT) and PI3K / Akt / mTOR protein in mouse renal cortex. Results The total flavonoids in mulberry leaves at high doses could significantly reduce the levels of blood glucose, serum creatinine, urea nitrogen and urine microalbuminuria in diabetic mice and increase the activation of PI3K / Akt / mTOR signaling pathway to increase the expression of the epithelial marker E- cadherin, reduce the interstitial markers α-SMA protein expression, improve renal tissue pathological changes. Conclusions Total flavonoids from mulberry leaves can reduce renal interstitial fibrosis in type 1 diabetic mice. The mechanism may be related to the inhibition of PI3K / Akt / mTOR signaling pathway.