普罗布考对小鼠肾缺血再灌注损伤的保护作用与机制  

Protective effect and mechanism of probucol on renal ischemia-reperfusion injury in mice

作　　者：龚淼[1] 张雷[1] 赵春芳[1] 李莉[1] 张亚楠[1] 任广伟[2] 

机构地区：[1]河北医科大学基础医学院组织胚胎学教研室,河北石家庄050017 [2]河北医科大学第一医院肾内科,河北石家庄050031

出　　处：《河北医科大学学报》2017年第5期497-500,505,共5页Journal of Hebei Medical University

基　　金：河北省医学科学研究重点课题(20170517)

摘　　要：目的探讨普罗布考对小鼠肾缺血再灌注(I/R)损伤的保护作用及其机制。方法选取雄性10周龄C57BL/6j小鼠40只随机分为4组各10只,分别为正常对照组、假手术组、I/R组、I/R+普罗布考灌胃组(100mg/kg)。石蜡切片HE染色观察小鼠肾脏形态学变化并进行肾小管病理改变评分;生化法检测小鼠血清肌酐(serum creatinine,SCr)和尿素氮(blood urea nitrogen,BUN)水平;比色法检测肾组织中丙二醛(malondialdehyde,MDA)含量和谷胱甘肽过氧化物酶(glutathione peroxidase,GPXs)活性;Western blot法检测肾组织GPX4蛋白表达。结果与正常对照组比较,IR组HE染色切片可观察到肾组织损伤,SCr和BUN水平显著升高,肾组织中MDA含量显著增高,GPXs活性和GPX4蛋白表达明显降低(P<0.01);与IR组比较,IR+普罗布考灌胃组肾组织损伤明显减轻,SCr和BUN水平显著降低,肾组织中MDA含量明显降低,GPXs活性和GPX4蛋白的表达明显升高(P<0.05)。结论普罗布考能减轻小鼠肾组织因急性缺血再灌注引起的损伤,其机制可能通过上调GPX4活性发挥肾组织保护作用。Objective To investigate the protective effect and mechanism of probucol on renal ischemia-reperfusion（I/R） injury in mice. Methods 10-week-old male C57BL/6j mice were randomly divided into four groups（n = 10）： control group, sham operation group, I/R group, and I/R＋probucol（100 mg/kg） group. The renal tissue pathological changes were observed by HE staining and graded. Levels of SCr and BUN in serum were tested by ELISA. The content of MDA and activity of GPXs were detected by using chromometry. The protein expression of GPX4 was measured by western blot. Results Compared with control group, pathological changes of renal tissue were aggravated in IR group. SCr and BUN levels as well as MDA content of renal tissue were significantly increased. We also found that GPXs activity and GPX4 protein expression were significantly decreased（P〈0.01）. Compared with IR group, histopathological changes of renal tissue were alleviated in IR＋ probueol group. The levels of Cr and BUN were decreased significantly, with MDA content decreased and GPXs activity or GPX4 protein increased（P〈0. 05）. Conclusion Probucol reduces thedamage of renal tissue induced by acute ischemia reperfusion injury in mice, which might be involved in activating GPX4.

关 键 词：再灌注损伤 肾 普罗布考 小鼠 

分 类 号：R619.9[医药卫生—外科学]