西地那非对肾缺血再灌注损伤大鼠氧化应激及肾小管细胞凋亡的影响  

Effects of sildenafil on the oxidative stress and renal tubular cell apoptosis in rats with renal ischemia-reperfusion injury

作　　者：王可娜 张娇 徐家云[1] WANG Kena;ZHANG Jiao;XU Jiayun(The First Affiliated Hospital of Henan University of Science and Technology,Luoyang 471000,China)

机构地区：[1]河南科技大学第一附属医院,河南洛阳471000

出　　处：《长春中医药大学学报》2022年第11期1217-1221,共5页Journal of Changchun University of Chinese Medicine

基　　金：2021年度河南省医学科技攻关计划软科学项目(LHGJ20210530)。

摘　　要：目的探究西地那非对肾缺血再灌注损伤(RIRI)大鼠氧化应激及肾小管细胞凋亡的影响,并分析可能的机制。方法40只SPF级SD雄性大鼠随机分为假手术组、模型组及西地那非低、中、高剂量组,每组8只。其中模型组、西地那非低、中、高剂量组均建立RIRI模型;西地那非低、中、高剂量组于缺血再灌注后立即腹腔注射25 mg·kg^(-1)·d^(-1)、50 mg·kg^(-1)·d^(-1)、75 mg·kg^(-1)·d^(-1)的盐酸西地那非溶液,连续2周;假手术组、模型组同时间腹腔注射等量生理盐水。观察各组肾组织病理学变化;测定各组24 h尿蛋白、血肌酐水平;测定各组氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;检测各组谷胱甘肽过氧化物酶(GSH-Px)活性;检测各组肾小管细胞凋亡情况;检测各组肾组织中凋亡相关因子(Fas)、半胱氨酸天冬氨酸蛋白酶-8(Caspase-8)蛋白水平。结果与假手术组比较,模型组及西地那非低、中、高剂量组24 h尿蛋白、血肌酐、MDA、AI、Fas、Caspase-8蛋白水平均升高(P<0.05),SOD、GSH-px水平降低(P<0.05);与模型组比较,西地那非低、中、高剂量组24 h尿蛋白、血肌酐、MDA、AI、Fas、Caspase-8蛋白水平降低(P<0.05),SOD、GSH-px水平升高(P<0.05),呈剂量依赖性。结论西地那非对RIRI大鼠肾组织发挥保护作用,可能是通过抑制肾组织氧化应激反应,抑制Fas/Caspase-8通路活化活化,进而抑制肾小管细胞凋亡实现的。Objective To investigate the effects of sildenafil on the oxidative stress and renal tubular cell apoptosis in rats with renal ischemia-reperfusion injury(RIRI),and analyze its possible mechanisms.Methods Forty male SPF SD rats were randomly divided into a sham operation group,a model group and low-,medium-and high-dose sildenafil groups,with 8 rats in each group.The RIRI models were established in the model group,the low-,middle-and high-dose sildenafil groups.In the low-,middle-and high-dose sildenafil groups,25 mg·kg^(-1)·d^(-1),50 mg·kg^(-1)·d^(-1) and 75 mg·kg^(-1)·d^(-1) hydrochloric acid sildenafil solution were intraperitoneally injected immediately after ischemia-reperfusion for 2 weeks.The sham operation group and model group were intraperitoneally injected with the same amount of normal saline at the same time.The renal histopathological changes were observed.The 24-hour urine protein and serum creatinine levels,the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in each group were measured.The activity of glutathione peroxidase(GSH-Px)and the apoptosis of renal tubular cells in each group were detected.The levels of apoptosis-related factors(Fas)and Caspase-8 protein in renal tissues of each group were detected.Results Compared with the sham operation group,the levels of the 24-hour urinary protein,serum creatinine,MDA,AI,Fas,Caspase-8 protein in the model group and the low-,middle-and high-dose sildenafil groups were increased(P<0.05),while the SOD,GSH-px levels were decreased(P<0.05).Compared with the model group,the levels of the 24-hour urinary protein,serum creatinine,MDA,AI,Fas,Caspase-8 protein in the low-,middle-and high-dose sildenafil groups were decreased(P<0.05),while the SOD,GSH-px levels were increased(P<0.05),in a dose-dependent manner.Conclusion Sildenafil has a protective effect on the renal tissues of RIRI rats,which may be achieved by inhibiting the oxidative stress response of renal tissues,inhibiting the activation of Fas/Caspase-8 pathway,and the

关 键 词：肾缺血再灌注损伤 西地那非 氧化应激 肾小管细胞凋亡 

分 类 号：R965[医药卫生—药理学]