TIR/BB环拟似物AS-1对小鼠肾缺血再灌注损伤的保护作用研究  

Protective effect of TIR/BB-loop mimetic AS-1 on renal ischemia/reperfusion injury in mice

作　　者：刁爱芹[1] 张光际 王卉[1] 潘爱萍[1] 袁海建[1] 李建涛[2] DIAO Aiqin;ZHANG Guangji;WANG Hui;PAN Aiping;YUAN Haijian;LI Jiantao(Medical Institute of Taizhou Polytechnic College,Taizhou 225300;Department of Pathophysiology,Nanjing Medical University,Nanjing 211166,China)

机构地区：[1]泰州职业技术学院医学技术学院,江苏泰州225300 [2]南京医科大学病理生理学系,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2022年第8期1080-1086,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：泰州市科技支撑计划(社会发展)项目(TS201912);泰州职业技术学院科研项目(TZYKY-18-21);泰州职业技术学院大学生创新创业训练计划项目(YJDC2020001)。

摘　　要：目的:研究TIR/BB环拟似物AS-1对小鼠肾脏缺血再灌注损伤的保护作用及机制。方法:雄性C57BL/6小鼠随机分成4组:假手术组(sham)、肾缺血再灌注组(RIR)、AS-1+肾缺血再灌注组(AS-1+RIR)、溶剂+肾缺血再灌注组(溶剂+RIR)。采用夹闭双侧肾动、静脉45 min,再灌注24 h的方法构建肾缺血再灌注损伤模型。AS-1+RIR组与溶剂+RIR组在术前30 min按剂量50 mg/kg分别腹腔注射AS-1和溶剂,再灌注24 h后检测肾功能参数、血清炎症因子、凋亡指标及磷酸化NF-κB p65(pp65)表达水平。结果:与假手术组比较,缺血再灌注组血清肌酐(Scr)、尿素氮(BUN)、TNF-α、IL-6、p-p65、Cleaved caspase3及Bax的表达水平均明显提高(P<0.01),肾间质CD68+和MPO炎症细胞浸润增多,Bcl-2的表达量明显降低(P<0.01),Bcl-2/Bax的比值也降低。给予AS-1处理后可以使Scr、BUN、TNF-α、IL-6、p-p65、Cleaved caspase3、及Bax的水平明显降低(P<0.01),CD68+和MPO炎症细胞浸润减少;Bcl-2的表达量升高(P<0.01),Bcl-2/Bax的比值也升高。结论:TIR/BB环拟似物AS-1对小鼠肾缺血再灌注损伤有保护作用,其机制可能与其抑制NF-κB信号通路的活化,产生抗炎作用和抗凋亡作用有关。Objective:To explore the effect and mechanism of TIR/BB-loop mimetic AS-1 on renal ischemia/reperfusion injury in mice.Methods:Male C57BL/6 mice were randomly and equally divided into four groups:sham operation group(Sham group),renal ischemia/reperfusion injury group(RIR group),AS-1+renal ischemia/reperfusion injury group(AS-1+RIR group),vehilce+renal ischemia/reperfusion injury group(vehilce+RIR group).The renal ischemia/reperfusion injury model was constructed by clipping bilateral renal veins for 45 min and reperfusion for 24 h.The AS-1+RIR group and vehilce+RIR group were intraperitoneally injected with 50 mg/kg AS-1 and vehicle 30 minutes before operation.After 24 h reperfusion,renal functional parameters,serum mediator concentrations,markers of apoptosis indexes and expression of phosphorylated NF-κB p65 were determined.Results:Serum creatinine(Scr)、blood ureanitrogen(BUN)、TNF-α、IL-6、Cleaved caspase3、Bax and p-NF-κB p65 were significantly increased after renal IR compared with the sham group(P<0.01).The expression of Bcl-2 and the ratio of Bcl-2/Bax were significantly decreased(P<0.01).After treatment with AS-1,the levels of Scr、BUN、TNF-α、IL-6、cleaved caspase 3、Bax and P-p65 were significantly decreased(P<0.01),the expression of Bcl-2 was increased(P<0.01),and the ratio of Bcl-2/Bax was also increased.Conclusion:TIR/BB loop analogue AS-1 has protective effect on renal ischemia-reperfusion injury in mice.The mechanism may be related to its anti-inflammatory and anti apoptotic effects by inhibiting the activation of NF-κB signaling pathway.

关 键 词：TIR/BB环拟似物AS-1 肾脏 缺血再灌注损伤 

分 类 号：R329.26[医药卫生—人体解剖和组织胚胎学]