姜黄素对大鼠重症急性胰腺炎相关性肾损伤的肾脏保护作用及机制探讨

Investigation on protective and therapeutic effects of Curcumin on rats with severe acute panceratitis associated renal injury

目的 探讨姜黄素对大鼠重症急性胰腺炎相关性肾损伤的肾脏保护作用及机制.方法 将健康SD大鼠72只随机分为假手术组(S组)、重症胰腺炎相关性肾损伤组(M组)、姜黄素治疗组(Cur组),每组24只.S组和M组在建模前3h分别予以1.5ml的生理盐水灌胃,而Cur组建模前3h予以200 mg/kg的1.5 ml姜黄素稀释液灌胃.M组和Cur组开腹后钝性分离胰腺周围韧带至胰头部,无创血管钳夹闭胰头3h后松开血管钳建立实验模型.造模成功后每组分别于12、24、36、48 h随机取6只大鼠测其腹水量及血淀粉酶、肌酐和尿素氮,取左肾行病理组织学观察;右肾组织行超氧化酶活性测定,实时定量聚合酶链反应(RT-PCR)检测缺氧诱导因子1 α(HIF-1α)mRNA.结果 各时间点M组的腹水量、血清淀粉酶、肌酐、尿素氮的检测值显著高于Cur组,而Cur组的HIF-1 αmRNA的表达量及超氧化酶的活性与M组比较升高明显(P均＜0.05);Cur组的肾脏和胰腺功能在各检测时间点相对于M组损伤更小,差异均有统计学意义(P均＜0.05).结论 姜黄素对大鼠重症急性胰腺炎相关性肾损伤有较好的保护作用,可能与通过上调HIF-1αmRNA的表达,提高超氧化酶活性,减少肾脏细胞的凋亡及坏死,提高肾脏耐缺氧能力有关.

Objective To investigate the effect of Curcumin on rats with severe acute pancreatitis associated renal injury and explore the possible mechanisms.Methods A total of 72 rats were randomLy divided into sham-operated group(S group, n =24), severe acute panceratitis with renal injury group(M group, n =24) ,Curcumin-treated group(Cur group,n=24).The S and M groups were given 1.5 ml saline through intragastric administration 3 hours before operation,while the Cur group was fed with same amount of Curcumin diluent(200 mg/kg).The pancreas and pancreatic tail-segment was dissociated and the head of pancreas was occlused in rats to form the model,blood vessel forceps was loosed after 3 hours.All the rats were sacrificed at 12 h,24 h, 36 h and 48 h after modeling.The level of ascites, serum amylase, creatinine, blood urea nitrogen were detected and the pathological chang of pancreas was observed under light microscope.Take the right kidney for Superoxide Dismutase (SOD) determination and the expression of hypoxia inducible factor-1αmRNA in the right kidney was detected with realtime polymerase chain reaction (RT-PCR).Results Compared with Cur group, the level of ascites, serum amylase, creatinine, blood urea nitrogen in M group were significantly increased, but the activity of SOD, the express of hypoxia inducible factor-1αmRNA had a significant decline (P＜0.05).The tissue damage of pancreas and the kidneys became more serious.But a better performance was to be found in the function of the Cur group's kidney and pancreas, and the the difference was statistical significance (P ＜0.05).Conclusion Curcumin has a good protective effect on severe acute pancreatitis associated renal injury.It may be through up-regulation expression of HIF-1α mRNA and increase the activity of superoxidase dismutase, then reduce the cell apoptosis and necrosis of the kidney, improve the ability of the kidney to tolerate hypoxia.