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目的观察桑酮碱(桑叶总黄酮和总生物碱)对2型糖尿病肾病大鼠的肾功能和肾TGF-β1/Smad信号通路的影响。方法以高脂联合链脲佐菌素复制2型糖尿病肾病大鼠模型,成模后分为模型组,二甲双胍组,桑酮碱低、中、高剂量组,另设正常空白组10只。灌胃给药,12周后测定各组大鼠空腹血糖及24 h尿量,尿液中白蛋白、肌酐的含有量;取血测定血清肌酐、尿素氮,并计算肌酐清除率;HE染色观察肾脏形态学的变化;Western bolt方法测定TGF-β1、Smad2/3、p-Smad2/3、IV型胶原(Co IV)、E钙黏蛋白(E-Ca)的蛋白表达水平;real time PCR方法检测Tgfb1、Co IV和E-Ca的mRNA表达水平。结果桑酮碱给药组能够显著降低糖尿病肾病大鼠空腹血糖、24 h尿量、尿白蛋白含有量及肌酐清除率,改善肾脏组织病理损伤,下调TGF-β1、p-Smad2/3、Co IV的表达,上调E-Ca表达。结论桑酮碱能延缓2型糖尿病大鼠早期肾病并发症的发生,其机制与调节肾脏TGF-β1/Smad信号通路有关。
Objective To observe the effects of berberine (total flavonoids and total alkaloids) on renal function and TGF-β1 / Smad signaling pathway in type 2 diabetic nephropathy rats. Methods High-fat and streptozotocin-induced diabetic nephropathy model rats were divided into model group, metformin group, low, medium and high dose of berberine, and another 10 normal control group. After 12 weeks, fasting blood glucose, 24 h urinary excretion, urinary albumin and creatinine were measured in all groups. Serum creatinine and urea nitrogen were measured by blood and creatinine clearance was calculated. HE staining The morphological changes of kidney were observed. The protein expression of TGF-β1, Smad2 / 3, p-Smad2 / 3, collagen IV and E-cadherin were detected by Western blot. The mRNA expression levels of Tgfb1, Co IV and E-Ca were examined. Results Fructose treatment group could significantly reduce the fasting blood glucose, 24 h urine volume, urinary albumin content and creatinine clearance in diabetic nephrosis rats, and improve renal histopathological injury, and down-regulate the expression of TGF-β1, p-Smad2 / 3, Co IV expression, up-regulation of E-Ca expression. Conclusion Mulcipinine can delay the occurrence of early nephropathy complications in type 2 diabetic rats, and its mechanism is related to the regulation of TGF-β1 / Smad signaling pathway in kidney.