增强自噬减轻大鼠造影剂所致急性肾损伤的实验研究

目的 建立造影剂所致急性肾损伤(CI-AKI)大鼠模型,探讨自噬在CI-AKI中的作用及机制.方法 将18只雄性Sprague-Dawley大鼠随机分为对照组(Con组)、CI-AKI组和雷帕霉素+造影剂组(Rapa组).CI-AKI组腹腔注射超大剂量的碘海醇(12.25 g/kg I),Rapa组于碘海醇注射前1周连续腹腔注射雷帕霉素(5 mg/(kg·d)),Con组腹腔注射等剂量的生理盐水.注射后24 h观察大鼠血肌酐水平、肾组织病理、肾组织中LC3Ⅱ/Ⅰ和Beclin-1表达水平及过氧化氢酶(CAT)含量的变化.结果 与Con组比较,CI-AKI组大鼠血肌酐水平明显升高((239.93±27.00) μmol/L比(51.70±10.59)μmol/L,P＜0.05),肾小管重度损伤,肾组织中自噬相关蛋白LC3Ⅱ/Ⅰ和Beclin-1表达均增加(均P＜0.05),而CAT含量减少((14.86±0.32)U/mg比(18.72±1.46)U/mg),差异具有统计学意义(P＜0.05).与CI-AKI组比较,雷帕霉素预处理增加了肾组织中LC3Ⅱ/Ⅰ和Beclin-1的表达及CAT含量((17.62±1.86)U/mg比(14.86±0.32)U/mg,P＜0.05),减轻了造影剂所致的肾小管损伤,并降低了血肌酐水平((187.62±47.76) μmol/L比(239.93±27.00) μmol/L),差异具有统计学意义(P＜0.05).结论 造影剂可诱导自噬激活,增强自噬可减轻造影剂所致氧化应激损伤及肾损伤.

Experimental study on attenuation of contrast-induced acute kidney injury by enhancing autophagy in rats

Objective To evaluate the effects of autophagy on contrast-induced acute kidney injury (CI-AKI) in rat models.Methods Eighteen male rats were divided into control group (Con),CI-AKI group (CI-AKI) and rapamycin-pretreated group (Rapa).In the CI-AKI group,CI-AKI was induced by intraperitoneal injection of iohexol (12.25 g/kg I).In the Rapa group,rapamycin was given by intraperitoneal injection with a dose of 5 mg/(kg ·d) for consecutive 7 days,and then injected with iohexol (12.25 g/kg I).Rats in the Con group were injected by the same dose of saline.The renal function,renal histopathology,and the levels of LC3 Ⅱ / Ⅰ and Beclin-1 as well as catalase (CAT) in the kidneys of rats were evaluated one day after the injection.Results Compared with the Con group,serum creatinine in the CI-AKI group was significantly increased ((239.93±27.00)μmol/L) vs (51.70±10.59) μmol/L,P＜0.05),and the content of CAT was significantly decreased ((14.86 ± 0.32) U/mg vs (18.72±1.46) U/mg,P＜0.05).In the CI-AKI group,renal tubules were severely injured,and the expression of autophagy-related proteins LC3 Ⅲ / Ⅰ and Beclin-1 in renal tissue was increased.Compared with the CI-AKI group,the pretreatment of rapamycin (Rapa group) increased the expression of LC3 Ⅱ / Ⅰ and Beclin-1 as well as the content of CAT in renal tissue ((17.62±1.86) U/mg vs (14.86±0.32) U/mg,P＜0.05),and inhibited the increase of contrast-induced serum creatinine ((187.62± 47.76) μmol/L vs (239.93±27.00) μmol/L,P＜0.05) and renal tubule injury.Conclusions The results showed that contrast administration can induce autophagy activation in kidneys,while enhancing autophagy can attenuate contrast-induced oxidative stress injury and related renal injury.