摘要
目的观察卡托普利灌胃后百草枯中毒急性肾损伤大鼠肾组织病理、TNF-α和NF-κB表达及血清IL-6水平变化,并探讨其意义。方法将54只雄性SD大鼠按随机数字法平均分成卡托普利组(Cap组)、染毒组(PQ组)及对照组(NS组),实验首日Cap组和PQ组利用百草枯溶液灌胃法建立急性肾损伤模型,NS组利用等量生理盐水建立空白对照; Cap组大鼠每日用卡托普利溶液灌胃,PQ组和NS组大鼠每日用生理盐水灌胃,常规饲养。于模型建立后第1、3、7天分三批次处置大鼠,每批次6只:麻醉后打开大鼠腹腔,取肾组织和血清。对各组大鼠肾组织进行HE染色,观察病理变化并评级;免疫组化法检测大鼠肾组织中TNF-α、NF-κB蛋白; q RT-PCR法检测大鼠肾组织中TNF-α、NF-κB mRNA; ELISA试剂检测大鼠血清IL-6。结果 PQ组大鼠肾间质可见大量浸润的炎性细胞,水肿、充血,肾皮质部可见肾小管上皮细胞出现明显的空泡变性及肿胀; Cap组肾间质的炎性细胞浸润情况、水肿充血及肾小管上皮细胞空泡变性等病理损伤较PQ组轻。Cap组和PQ组在各时间点大鼠肾组织中TNF-α、NF-κB蛋白和mRNA的表达量及血清IL-6水平均高于NS组(P均<0. 05); Cap组第3、7天大鼠肾组织中TNF-α、NF-κB蛋白和mRNA的表达量及血清IL-6水平均低于PQ组(P均<0. 05)。Cap组第7天大鼠肾组织中TNF-α、NF-κB蛋白和mRNA的表达量及血清IL-6水平较第1、3天降低(P均<0. 05); PQ组第3天大鼠肾组织中TNF-α、NF-κB蛋白和mRNA的表达量及血清IL-6水平较第1、7天升高(P均<0. 05)。结论百草枯致大鼠肾损伤时,卡托普利可以减轻肾间质的炎性细胞浸润、水肿充血及肾小管上皮细胞空泡变性等病理损伤,抑制肾组织中NF-κB、TNF-α的表达并降低血清IL-6的水平,这可能是卡托普利治疗百草枯中毒导致急性肾损伤的作用机制之一。
Objective To observe the changes of renal histopathology,TNF-αand NF-κB expression and serum IL-6 level in rats with acute renal injury caused by paraquat poisoning after gavage of captopril.Methods Fifty-four male SD rats were divided into captopril group(Cap group),paraquat poisoning group(PQ group)and control group(NS group).On the first day of the experiment,the acute kidney injury model was established by paraquat solution intragastric administration in the Cap group and PQ group.Rats in the Cap group were given captopril solution daily,and rats in the PQ group and NS group were given normal saline daily.After the establishment of the model,six rats were sacrificed at 1,3,and 7 d,and after anesthesia,renal tissues and serum were taken.The renal tissues of each group were stained with HE staining,and the pathological changes were observed and graded.Immunohistochemical method was used to detect TNF-αand NF-κB protein in the rat kidney tissues.TNF-αand NF-κB mRNA levels were detected by qRT-PCR,and the serum IL-6 was detected by ELISA.Results A large number of infiltrated inflammatory cells,edema and hyperemia were observed in the renal interstitium of rats in the PQ group,and obvious vacuolar degeneration and swelling were observed in renal tubular epithelial cells in the renal cortex.In the Cap group,inflammatory infiltration of renal interstitial cells,edema and hyperemia,and vacuolar degeneration of renal tubular epithelial cells were reduced as compared with those of the PQ group.The expression levels of TNF-α,NF-κB protein and mRNA,and serum IL-6 level in the kidney tissues of the Cap and PQ groups were higher than those in the NS group(all P<0.05).The expression levels of TNF-α,NF-κB protein and mRNA,and serum IL-6 level in the kidney of rats in the Cap group on day 3 and 7 were significantly lower than those in the PQ group(all P<0.05).On day 7 of the Cap group,the expression levels of TNF-α,NF-κB protein and mRNA,and serum IL-6 level in the renal tissues of rats were decreased as compared
作者
李霁
张剑锋
卢俊宇
叶喆
周志兵
罗毅沣
李帅
LI Ji;ZHANG Jianfeng;LU Junyu;YE Zhe;ZHOU Zhibing;LUO Yifeng;LI Shuai(The Second Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)
出处
《山东医药》
CAS
2018年第47期47-51,共5页
Shandong Medical Journal
基金
国家自然科学基金资助项目(81360290)
国家自然科学基金地区项目(81660132)
广西自然科学基金资助项目(2017GXNSFAA198249)
广西自然科学基金青年基金资助项目(2017GXNSFBA198043)
