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
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E-mail:ljt@njmu.edu.cn

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R329.26

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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)


Protective effect of TIR/BB⁃loop mimetic AS⁃1 on renal ischemia/reperfusion injury in mice
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    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(p⁃ p65)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。

    Abstract:

    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 ⁃ κ B signaling pathway.

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刁爱芹,张光际,王卉,潘爱萍,袁海建,李建涛. 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[J].南京医科大学学报(自然科学版),2022,42(8):1080-1086

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  • 在线发布日期: 2022-08-07
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