内皮素A受体拮抗剂BQ123对腺嘌呤诱导慢性肾贫血模型大鼠的肾保护作用及机制研究  

Protective effect and mechanism of Endothelin A receptor antagonist BQ123 on adenine induced chronic renal anemia in rats

作　　者：徐江维 王刚祚 葛一蓉 XU Jiang-wei;WANG Gang-zuo;GE Yi-rong.(1.Department of Pediatrics,Enshi Tujia Miao Autonomous Prefecture Central Hospital,Enshi Hubei 445000,China)

机构地区：[1]恩施土家苗族自治州中心医院儿科,湖北恩施445000

出　　处：《临床和实验医学杂志》2018年第13期1355-1359,共5页Journal of Clinical and Experimental Medicine

摘　　要：目的研究内皮素A受体拮抗剂BQ123对腺嘌呤诱导慢性肾贫血模型大鼠肾功能的保护作用并探讨其作用机制。方法采用腺嘌呤诱导法制备慢性肾贫血模型大鼠,随机分为空白对照组、模型组、西他生坦组(50 mg/kg)、BQ123低(5μg/kg)、中(25μg/kg)、高(75μg/kg)剂量组,模型组及空白对照组给予等量生理盐水灌胃。连续用药10周,检测各组大鼠肾功能,苏木素-伊红(HE)染色观察肾组织病理学变化,透射电子显微镜观察肾组织中细胞自噬小体数量,蛋白印迹(WB)法检测肾组织中微管相关蛋白1轻链3(LC3-Ⅱ)、自噬相关蛋白Beclin1、丝氨酸/苏氨酸蛋白激酶(Akt)、雷帕霉素(mTOR)、p-Akt、p-mTOR蛋白表达情况。结果与空白对照组比较,模型组大鼠肾组织出现水肿、纤维化、萎缩等病理损伤,组织病理评分明显升高,肾功能显著下降,血液中血清肌酐(Scr)、血尿素氮(BUN)水平显著升高,自噬小体数目明显减少,LC3-Ⅱ、Beclin蛋白表达显著下调,p-Akt、p-mTOR蛋白表达明显上调;与模型组比较,BQ123低、中、高剂量组大鼠肾组织病理变化均显著改善,组织病理评分明显降低,肾功能显著恢复,自噬小体数目显著增多,LC3-Ⅱ、Beclin蛋白表达显著上调,p-Akt、p-mTOR蛋白表达显著下调,均呈剂量依赖效应。结论 BQ123可能通过抑制Akt/mTOR信号通路激活促进自噬小体的形成,发挥对腺嘌呤诱导的慢性肾贫血大鼠肾功能的保护作用。Objective To study the protective effect of endothelin A receptor antagonist BQ123 on the renal function of rats with adenine-induced chronic renal anemia and to explore its mechanism of action. Methods Chronic renal anemia model rats were prepared by adenine induction,and were randomly divided into model group,Sitaxentan group（ 50 mg/kg）,low（ 5 μg/kg）,medium（ 25 μg/kg）,high（ 75 μg/kg）dose BQ123 group,and the model group and blank control group were given the same physiological saline. Drug was used continuously for 10 weeks,renal function of rats in each group was detected,the pathological changes of renal tissue were observed by hematoxylin eosin（ HE） staining,the number of autophagosomes in the renal tissue was observed by transmission electron microscopy,Western blot（ WB） was used to detect the expressions of microtubule associated protein 1,microtu-bule associated protein 1 light chain 3（ LC3-Ⅱ）,autophagy related protein Beclin1,serine/threonine protein kinase（ Akt）,rapamycin（ mTOR）,p-Akt and p-mTOR in renal tissues. Results Compared with the blank control group,the renal tissue of the model rats appeared pathological injury like edema,fibrosis and atrophy,histopathological score increased significantly,renal function decreased significantly,blood serum creatinine（ Scr）,blood urea nitrogen（ BUN） levels were significantly increased,the number of autophagosomes were significantly decreased,the expressions of LC3-Ⅱ,Beclin protein were significantly decreased,the expressions of p-Akt and p-mTOR protein were significantly increased; Compared with the model group,pathological change of renal tissue disease in rats of the BQ123 low,medium and high dose groups were significantly improved,the histopathological score was significantly decreased,the renal function recovered significantly,the number of autophagosomes increased significantly,the expressions of LC3-Ⅱ and Beclin protein were significantly up-regulated,the expressions of p-Akt and p-mTOR protein were sign

关 键 词：大鼠 慢性肾贫血 腺嘌呤 BQ123 肾功能 细胞自噬 

分 类 号：R-332[医药卫生] R556R692