增强自噬减轻大鼠造影剂所致急性肾损伤的实验研究

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

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＆#183;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.

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 ＆#183;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.