摘要
目的观察硫化氢是否可以通过调节Nrf2/HO-1通路减轻大鼠肾脏缺血再灌注损伤。方法选取24只雄性SD大鼠,随机分为假手术组(sham组)、肾脏缺血再灌注(ischemia/reperfusion,I/R)组、I/R+NaHS组,每组8只。I/R组及I/R+NaHS组用微动脉夹夹闭左肾蒂45 min后解除,建立缺血性急性肾损伤模型;sham组不给予夹闭,余操作与I/R组及I/R+NaHS组相同。24 h后留取各组肾组织和血标本。Western blot法检测Nrf2及其下游HO-1蛋白表达;比色法检测肾组织SOD、MDA含量;用ROS荧光探针、二氢乙锭(DHE)染色、荧光显微镜下观察肾组织ROS表达;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测肾组织细胞凋亡情况;比色法检测血中尿素氮(BUN)及肌酐(Scr)水平评估肾功能;HE染色法观察肾脏组织学改变。结果与sham组相比,I/R组肾组织Nrf2、HO-1蛋白表达增加(P<0.05),SOD活性下降、MDA含量增高(P<0.01),ROS表达增加(P<0.01),血清肌酐、尿素氮显著增高(P<0.05),肾小管损伤加重(P<0.01),凋亡细胞明显增加(P<0.05)。与I/R组相比,I/R+NaHS组肾组织Nrf2、HO-1蛋白表达增加(P<0.05),SOD活性升高、MDA含量降低(P<0.01),ROS表达减少(P<0.01),血清肌酐、尿素氮降低(P<0.05),肾小管损伤减轻(P<0.01),凋亡细胞减少(P<0.05)。结论硫化氢可能通过调节Nrf2/HO-1通路减轻大鼠肾缺血再灌注损伤。
Objective To observe whether hydrogen sulfide can alleviate renal ischemia reperfusion injury in rats by regulating Nrf2/HO-1 pathway.Methods Twenty-four male SD rats were randomly divided into sham group,ischemia/reperfusion(I/R)group and I/R+NaHS group,with 8 rats in each group.The left renal pedicle was clipped with an arteriole clamp for 45 min and subsequently released to establish the ischemia acute kidney injury model in I/R group and I/R+NaHS group.The rats in sham group did not receive clipping,and the residual procedures were identical to those in I/R group and I/R+NaHS group.The kidney tissue and blood samples were taken at 24 h.The protein expression levels of Nrf2 and its downstream target HO-1 protein were detected by Western blot.The contents of SOD and MDA were detected by colorimetry.ROS expression in renal tissue was observed by fluorescence probe and DHE staining.Terminal deoxynucleotide transferase-mediated dUTP notch end labeling(TUNEL)assay was used to detect the apoptosis of renal cells.The levels of blood urea nitrogen(BUN)and creatinine(Scr)were measured using colorimetry to assess renal function of kidney,and the histological changes of kidney were observed by HE staining.Results Compared with sham group,the protein expression levels of Nrf2 and HO-1 in renal tissues in I/R group were increased(P<0.05),SOD activity was decreased,MDA content was increased(P<0.01),ROS expression was increased(P<0.01),serum levels of creatinine and urea nitrogen were significantly increased(P<0.05),renal tubular injury was aggravated(P<0.01),and the apoptosis cells were significantly increased(P<0.05).Compared with I/R group,the expression levels of Nrf2 and HO-1 proteins in I/R+NaHS group were increased(P<0.05),SOD activity was increased(P<0.01),MDA content was decreased(P<0.01),ROS expression was decreased(P<0.01),serum levels of creatinine and urea nitrogen were decreased(P<0.05),renal tubular injury was alleviated(P<0.01),and the apoptosis cells were decreased(P<0.05).Conclusion Hydrogen sulfide may red
作者
闫琰
张文文
董毅玲
覃志成
YAN Yan;ZHANG Wenwen;DONG Yiling;TAN Zhicheng(Department of Nephrology,Fifth Clinical Medical College of Shanxi Medical University,Taiyuan 030012,China;Shanxi Provincial Key Laboratory of Nephrology)
出处
《山西医科大学学报》
CAS
2022年第6期713-718,共6页
Journal of Shanxi Medical University
基金
山西省“136”兴医工程专项基金项目(SZ2019011)。
