羟考酮预给药对大鼠肾缺血-再灌注损伤的影响

摘要

目的 评价羟考酮预给药对大鼠肾缺血-再灌注损伤的影响.方法 健康成年雄性SD大鼠30只,采用随机数字表法,将其分为三组(n=10),假手术组(S组):仅切除右肾、分离左侧肾动脉、肾静脉和输尿管;缺血-再灌注组(IR组):切除右侧肾脏,夹闭左侧肾动脉和肾静脉45 min恢复灌注2h;羟考酮预给药十缺血-再灌注组(O组):缺血-再灌注前5 min静脉注射羟考酮2 mg/kg.于再灌注2h时经腹主动脉采集动脉血样,血清尿素氮(BUN)浓度采用脲酶法测定,血清肌酐(Cr)浓度采用速率法测定.处死大鼠,取部分左肾组织,超氧化物歧化酶(SOD)活性采用黄嘌呤氧化酶法测定,丙二醛(MDA)含量采用硫代巴比妥酸法测定.采用Western blot检测肾组织中B细胞淋巴瘤/白血病-2(bcl-2)、B细胞淋巴瘤/白血病-2相关x蛋白(bax)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白表达.结果 与S组比较,IR组和O组血清BUN和Cr的浓度明显升高(P＜0.05),肾组织MDA的含量明显升高,SOD活性明显降低(P＜0.05),肾组织bax、Caspase-3蛋白表达明显升高(P＜0.05),而bcl-2蛋白表达明显降低(P＜0.05).与IR组比较,O组血清BUN和Cr的浓度明显降低(P＜0.05),肾组织MDA的含量明显降低,SOD活性明显升高(P＜0.05)肾组织bax、Caspase-3蛋白表达明显降低(P＜0.05),而bcb2蛋白表达明显升高(P＜0.05).结论 羟考酮预给药可减轻大鼠肾缺血-再灌注损伤,其机制可能与其抑制肾组织氧化应激反应和细胞凋亡有关.%Objective To evaluate the effects of oxycodone pretreatment on renal ischemiareperfusion(IR) injury in rats.Methods Thirty adult male Sprague-Dawley rats were randomly divided into 3 groups (n=10 each) using a random number table:sham operation group(group S),group IR,and oxycodone pretreatment +IR group (group O).After removing the right kidney in rats,the renal I/R was built by occlusion of the left renal artery and vein for 45 min with a traumatic microclips followed by 2 h reperfusion in I/R and O group.In group S,the right kidney was performed and the left renal artery,vein and ureter were isolated without occluding blood flow.In group O,oxycodone 2 mg/kg were infused intravenously 5 min before onset of ischemia.At 2 h of reperfusion,blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen(BUN)and creatinine(Cr).After blood sampling,the rats were sacrificed,and the left kidney were removed for determination of malondialdehyde(MDA) content (by thiobarbituric acid method) and superoxide dismutase (SOD) activity (using xan-thine oxidase method).The expression levels of B-cell lymphoma-2 (bcl-2),bcl-2 Assaciated X protein(bax) and cycteinyl aspirate-specific protease-3 (Caspase-3) protein were detected by Western blotting,respectively.Results Compared with group S,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly increased,the content of bcl-2 and SOD activity in renal tissues were significantly decreased in the other two groups(P＜0.05).Compared with group IR,the serum BUN and Cr concentrations,and the contents of MDA,bax and Caspase-3 in renal tissues were significantly decreased,the content of bcl-2 and SOD activity in renal tissues were significantly increased in group O (P＜0.05).Conclusion Oxycodone can alleviate renal I/R injury in rats,and the mechanism is related to inhibition of oxidative stress response and cell apoptosis.