摘要
目的探讨血管紧张素转换酶抑制剂卡托普利在肾缺血再灌注损伤中治疗机制。方法取雄性Wistar大鼠75只随机分为假手术组（Sham组，n=25），缺血再灌注损伤组（I／R组，n=25），卡托普利治疗组（CAP组，n=25）。采用结扎一侧大鼠肾血管制备缺血再灌注损伤模型，检测血清肌酐、尿素氮值，病理切片观察各组肾组织变化，采用ELISA检测各组肾组织和血清中炎症细胞因子IL-6、IL－8、TNF－α的变化，通过磷酸化抗体、Westernblot分析炎症信号通路中丝裂原激活的蛋白激酶（mito—genactivated protein kinase，MAPK）信号通路的活化程度。结果卡托普利治疗后，I／R组与CAP组肌酐、尿素氮水平均高于Sham组（P〈0．05），CAP组肌酐、尿素氮的浓度均低于I／R组（P〈0．05）。I／R组IL-6、IL-8、TNF-α的浓度高于Sham组（P〈0．05）；卡托普利治疗后，CAP组IL－6、IL－8、TNF－α的浓度低于I／R组（P〈0．05）。I／R组与CAP组肾组织中c-jun氨基端激酶（c-junN．terminalkinase，JNK）、胞外信号调节蛋白激酶（extracellular signal—regulated kinase，ERK）、P38均被磷酸化，且两组间无明显差异。结论卡托普利可在一定程度上改善肾功能，抑制IL-6、IL-8、TNF-α等炎症因子的表达，但不是通过抑制MAPK通路来抑制炎症因子的表达。
Objective To explore therapeutic mechanism of angiotensin-converting enzyme inhibitor （Captopril） in renal ischemia reperfusion （I/R） injury. Methods Wistar rats were randomly divided into sham operation group （ Sham group）, ischemia-reperfusion group （ I/R group）, captopril-treated group （ CAP group ）, I/R model was made through ligating one side renal vessel. Renal function indexes including SCr and BUN were detected through biochemical analysis. Changes of renal tissue were observed by pathological section. ELISA detection was used to determine inflammatory cytokines such as IL-6, IL-8 and TNF-cc Activation of MAPK signaling pathway were analyzed by Western blot. Results After captopril treatment, SCr, BUN levels of the I/R group and the CAP group were higher than those of Sham group （ P 〈 0. 05 ）, Scr, BUN concentrations of CAP group were lower than those of I/R group（ P 〈 0. 05 ）. After captopril treatment, IL-6, IL-8,TNF-α concentrations of IZR group were higher than those of the Sham group（ P 〈 0. 05 ） ; IL-6, IL-8, TNF-α concentrations of CAP group were lower than those of I/R group（ P 〈 0. 05）. Renal tissue c-jun N-terminal kinase, extracellular signal-regulated protein kinases, P38 in I/R group and CAP group were phosphorylated, and there were no significant differences between the two groups. Conclusion Captopril could improve renal function to some degree, and reduce expression of inflammatory cytokines rather than MAPK inflammatory signaling pathway.
出处
《中国小儿急救医学》
CAS
2015年第12期836-839,843,共5页
Chinese Pediatric Emergency Medicine
基金
湖南省卫生厅资助项目（B2007155）
