大黄素对大鼠重症急性胰腺炎相关性肾损伤缺氧诱导因子-1α的影响

Effects of Emodin on the Expression of Hypoxia Inducible Factor-1α Protein in Rats with Severe Acute Pancreatitis-associated Renal Injury

目的探讨大黄素对大鼠重症急性胰腺炎时肾脏组织缺氧诱导因子-1α(HIF-1α)表达的影响及其对相关性肾损伤的保护机制。方法将72只健康Sprague Dawley大鼠随机分为假手术组、重症急性胰腺炎相关性肾损伤组(损伤组)、大黄素治疗组(治疗组),每组24只。造模前3 h及造模后每12小时,假手术组和损伤组分别予以生理盐水灌胃,治疗组以大黄素灌胃。造模完成后每组分别于12、24、36 h各随机取8只大鼠检测其腹水量,血淀粉酶、肌酐、尿素氮水平,再取左肾组织行苏木精-伊红染色观察肾脏病理组织变化及免疫组织化学染色检测HIF-1α蛋白的表达情况。结果各时间点损伤组及治疗组的腹水量、血淀粉酶、肌酐、尿素氮水平及HIF-1α蛋白的表达水平均明显高于假手术组(P<0.05);与损伤组比较,治疗组胰腺及肾脏组织的损伤明显减轻,而HIF-1α蛋白的表达水平更高(P<0.05)。结论大黄素可能主要通过上调HIF-1α蛋白的表达,提高肾脏细胞耐缺氧的能力来发挥对重症急性胰腺炎相关性肾损伤的保护作用。

Objective To investigate the effect of emodin on the expression of hypoxia inducible factor（HIF）-1α protein in 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（n=24）,severe acute pancreatitis with renal injury group（injury group,n=24）,and treatment group（n=24）.The sham-operated and injury groups were given 1.5 mL saline through intragastric administration before operation while the treatment group was fed with the same amount of 50 mg/kg emodin diluent.The pancreas and pancreatic tail-segment was dissociated and the head of pancreas was occluded in rats to form the model,and blood vessel forceps were loosed after three hours.All the rats were sacrificed 12,24 and 36 hours after modeling.The level of ascites,serum amylase,creatinine,blood urea nitrogen were detected.Hematoxylin-eosin staining was used to observe the pancreatic and renal pathological changes,and immunohistochemical method was used to detect the expression of HIF-1α protein level in the kidney.Results Compared with the sham-operated group,the level of ascites,serum amylase,creatinine,blood urea nitrogen and the expression of HIF-1α protein level increased significantly.The tissue damage of pancreas and the kidney became more serious.Compared with the injury group,the kidney and pancreas function of the treatment group had a better performance.HIF-1α protein level significantly increased in the treatment group,and the difference had a statistical significance（P〈0.05）.Conclusions Emodin has a good protective effect on severe acute pancreatitis-associated renal injury.It may function through up-regulation expression of HIF-1α protein level to improve the ability of the kidney to tolerate hypoxia,and then reduce the cell apoptosis and necrosis of the kidney.