厄洛替尼減輕STZ誘導(dǎo)的糖尿病腎病模型大鼠的腎損傷
發(fā)布時(shí)間:2018-05-27 18:19
本文選題:糖尿病腎病 + 厄洛替尼; 參考:《中國(guó)病理生理雜志》2017年08期
【摘要】:目的:研究表皮生長(zhǎng)因子受體(EGFR)抑制劑厄洛替尼(erlotinib)對(duì)糖尿病腎病大鼠腎臟的保護(hù)作用及機(jī)制。方法:采用大劑量(55 mg/kg)鏈脲佐菌素(STZ)腹腔注射誘導(dǎo)大鼠糖尿病腎病模型,以1周后血糖值16.7 mmol/L的大鼠為造模成功的標(biāo)準(zhǔn)。將糖尿病大鼠隨機(jī)分為2組[STZ組和STZ+erlotinib(100 mg·kg~(-1)·d~(-1))組],并以正常大鼠為對(duì)照組(control組)。Erlotinib處理4周后,檢測(cè)大鼠空腹血糖、血清肌酐和24 h尿蛋白含量的變化;HE染色和Masson染色觀察腎臟組織病理學(xué)改變;Western blot檢測(cè)各組腎臟組織中EGFR、p-EGFR、轉(zhuǎn)化生長(zhǎng)因子β1(TGFβ1)、Smad2/3、p-Smad2/3、Ⅳ型膠原蛋白(ColⅣ)和纖連蛋白(fibronectin)的蛋白水平;活性氧簇(ROS)和丙二醛(MDA)試劑盒分別檢測(cè)各組腎臟組織中ROS和MDA水平。結(jié)果:與control組相比,STZ組血糖、24 h尿蛋白和血清肌酐水平均顯著升高(P0.01),腎組織形態(tài)學(xué)出現(xiàn)異常變化;與STZ組相比,STZ+erlotinib組的血糖、24 h尿蛋白水平和血清肌酐水平顯著降低(P0.05),腎小球結(jié)構(gòu)恢復(fù)正常,腎小球系膜細(xì)胞增生程度明顯減弱。厄洛替尼明顯抑制了STZ大鼠腎組織中p-EGFR、TGFβ1、p-Smad2/3、ColⅣ和fibronectin蛋白水平,也明顯抑制了STZ大鼠腎組織中ROS和MDA水平。結(jié)論:厄洛替尼可能通過(guò)抑制EGFR/TGFβ1-Smad2/3信號(hào)通路的激活來(lái)抑制糖尿病腎病腎組織的纖維化和氧化應(yīng)激反應(yīng),從而減輕腎損傷。
[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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