厄洛替尼减轻STZ诱导的糖尿病肾病模型大鼠的肾损伤

发布时间：2018-05-27 18:19

  本文选题：糖尿病肾病 + 厄洛替尼　； 参考：《中国病理生理杂志》2017年08期

【摘要】：目的:研究表皮生长因子受体(EGFR)抑制剂厄洛替尼(erlotinib)对糖尿病肾病大鼠肾脏的保护作用及机制。方法:采用大剂量(55 mg/kg)链脲佐菌素(STZ)腹腔注射诱导大鼠糖尿病肾病模型,以1周后血糖值16.7 mmol/L的大鼠为造模成功的标准。将糖尿病大鼠随机分为2组[STZ组和STZ+erlotinib(100 mg·kg~(-1)·d~(-1))组],并以正常大鼠为对照组(control组)。Erlotinib处理4周后,检测大鼠空腹血糖、血清肌酐和24 h尿蛋白含量的变化;HE染色和Masson染色观察肾脏组织病理学改变;Western blot检测各组肾脏组织中EGFR、p-EGFR、转化生长因子β1(TGFβ1)、Smad2/3、p-Smad2/3、Ⅳ型胶原蛋白(ColⅣ)和纤连蛋白(fibronectin)的蛋白水平;活性氧簇(ROS)和丙二醛(MDA)试剂盒分别检测各组肾脏组织中ROS和MDA水平。结果:与control组相比,STZ组血糖、24 h尿蛋白和血清肌酐水平均显著升高(P0.01),肾组织形态学出现异常变化;与STZ组相比,STZ+erlotinib组的血糖、24 h尿蛋白水平和血清肌酐水平显著降低(P0.05),肾小球结构恢复正常,肾小球系膜细胞增生程度明显减弱。厄洛替尼明显抑制了STZ大鼠肾组织中p-EGFR、TGFβ1、p-Smad2/3、ColⅣ和fibronectin蛋白水平,也明显抑制了STZ大鼠肾组织中ROS和MDA水平。结论:厄洛替尼可能通过抑制EGFR/TGFβ1-Smad2/3信号通路的激活来抑制糖尿病肾病肾组织的纤维化和氧化应激反应,从而减轻肾损伤。
[Abstract]:Aim: to study the protective effect and mechanism of epidermal growth factor receptor (EGFR) inhibitor erlotinib on kidney of diabetic nephropathy rats. Methods: the diabetic nephropathy model was induced by intraperitoneal injection of high dose of 55 mg / kg streptozotocin (STZ) in rats. Diabetic rats were randomly divided into two groups [STZ group and STZ erlotinib(100 mg KG-1) group]. The control group was treated with Erlotinib for 4 weeks, and fasting blood glucose was measured. The changes of serum creatinine and 24 h urine protein contents. The histopathological changes of kidney were observed by HE staining and Masson staining. The protein levels of EGFRP-EGFR, TGF- 尾 1(TGF 尾 1, Smad2 / 3p-Smad2 / 3, collagen 鈪，

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