摘要
目的研究高迁移率族蛋白-1(HMGB1)在重症急性胰腺炎(SAP)大鼠肺损害的机理以及乌司他丁的干预效应。方法将54只SD大鼠随机分为对照组、SAP组和乌司他丁治疗组三组,每组各18只,每组再分为6h、12h和24h亚组(n=6)。以5%的牛磺胆酸造模SAP,对照组开腹并拨动胰腺组织,而治疗组在SAP基础上予乌司他丁干预。检测胰腺及肺组织的病理学及血氧分压改变;免疫法检测胰腺的HMGB1的水平;ELISA法检测胰腺、肺及血中的TNF-α、HMGB1、IL-1β蛋白浓度。结果 SAP组在血、胰腺、肺中的HMGB1蛋白浓度在6~24h持续上升,SAP组、治疗组明显高于对照组,差异均有统计学意义(P<0.05);SAP组血清中的IL-1β、TNF-α蛋白浓度在6~12h持续上升,于24h开始降低,SAP组、治疗组明显高于对照组且差异均有统计学意义(P<0.05);SAP组胰腺可见HMGB1强表达:SAP组>治疗组>对照组,从6~24h保持上升趋势,差异均有统计学意义(P<0.05)。结论 SAP大鼠的炎症机制可能是由于HMGB1部分结合TNF-α、IL-1β并通过JNK信号通路而导致的,而乌司他丁能降低SAP大鼠肺组织中HMGB1、TNF-α、IL-1β表达及中断JNK信号通路,能有效治疗SAP大鼠的胰腺及肺损伤。
Objective To investigate the mechanism of HMGB1 in lung injury in rats with severe acute pancreatitis and the intervention effect of ulinastatin severe acute pancreatitis. Methods Fifty-four SD rats were randomly divided into control group, SAP group and ulinastatin group. The three groups were divided into 6h, 12h and 24h subgroups （n= 6）, respectively. The control group was treated with pancreas opened. SAP group was prepared with 5% taurocholic acid. The treatment group was injected with ulinastatin on the basis of the tail vein. The levels of HMGB1, TNF-α and IL-β in serum, pancreas and lung tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Envision immunoassay was used to detect the expression of HMGB1 in pancreatic tissue. Results The concentration of HMGB1 protein in the pancreas, lung tissue and serum began to increase at 6 h, rapidly increased at 12 h, and increased in the SAP group and the control group at 24 h, which was significantly higher than that in the control group （P〈0.05）. The concentration of IL-1β and TNF-α in SAP group Began to increase at 6 h, and continued to rise at 12 h, and decreased in 24h group. The SAP group and control group were significantly higher than those in control group （P〈0.05）. SAP group showed strong expression of HMGB1 in the pancreas. Conclusion The inhibitory effect of HMGB1 on the pancreas of SAP rats may be partially combined with TNF-α, IL-1β and JNK signaling pathway. Ulinastatin can decrease the expression of HMGB1 and TNF-α, IL-1β expression. Interrupt JNK signaling pathway can effectively treat lung injury in SAP rats.
出处
《西部医学》
2018年第2期174-177,181,共5页
Medical Journal of West China
基金
自贡市科技局重点科技计划项目(2016ZC37)
