HMGB1、TLR4在重症急性胰腺炎大鼠胰腺组织中的表达及乌司他丁的干预效应

发布时间：2019-02-17 16:21

【摘要】：目的探讨HMGB1、TLR4在重症急性胰腺炎大鼠胰腺组织中的作用机制以及乌司他丁的干预效应。方法将54只SD大鼠分为对照组、SAP组和乌司他丁治疗组,3组又分为6、12h和24h3个小组(每小组n=6)。对照组开腹后仅翻动胰腺组织,SAP组用5%的牛磺胆酸钠制备SAP模型,治疗组在SAP造模成功后经尾静脉注射乌司他丁。观察3组大鼠胰腺组织的病理学改变;EPS-G7法检测血清中的淀粉酶;ELISA法检测血清及胰腺组织中的HMGB1;Envision两步免疫法检测胰腺组织中的HMGB1、TLR4的表达水平。结果 SAP组、治疗组各时间点的淀粉酶与对照组比较明显升高,病理学改变明显,差异均有统计学意义(P0.05),示SAP造模成功;SAP组在胰腺组织及血清中的HMGB1表达在6h开始升高,于12h快速上升,至24h保持上升趋势,与对照组大鼠相同时间点比较明显升高,差异有统计学意义(P0.05),治疗组与SAP组相同时间点的HMGB1比较明显降低,差异有统计学意义(P0.05);SAP组胰腺组织中的TLR4表达在6h开始升高,12h达高峰,24h开始下降,与对照组大鼠相同时间点比较明显升高,差异有统计学意义(P0.05)。治疗组与SAP组相同时间点的TLR4比较明显降低,差异有统计学意义(P0.05)。结论 HMGB1在SAP大鼠胰腺中的致炎作用可能是部分结合其受体TLR4并通过MyD88依赖性途径而实现的,而乌司他丁可能是通过中断SAP大鼠胰腺组织中的HMGB1、TLR4信号通路发挥保护作用。
[Abstract]:Objective to investigate the mechanism of HMGB1,TLR4 in pancreatic tissue of rats with severe acute pancreatitis and the intervention effect of ulinastatin. Methods 54 SD rats were divided into three groups: control group, SAP group and ulinastatin treatment group. The 3 groups were divided into 6 groups (n = 12) and 24h3 group (n = 6). SAP group was treated with 5% sodium taurocholate to make SAP model, and the treatment group was injected with ulinastatin via tail vein after successful SAP. The histopathological changes of pancreatic tissue in the three groups were observed; the amylase in serum was detected by EPS-G7 method; and the expression of HMGB1,TLR4 in pancreatic tissue was detected by two-step immunoassay of HMGB1;Envision in serum and pancreatic tissue by ELISA method. Results in the SAP group, the amylase in each time point in the treatment group was significantly higher than that in the control group, and the pathological changes were significant (P0.05). The results showed that the SAP model was successful. The expression of HMGB1 in pancreatic tissue and serum of SAP group began to increase at 6 h, increased rapidly at 12 h, and maintained an increasing trend at 24 h. The expression of HMGB1 in SAP group was significantly higher than that in control group at the same time point (P0.05). The HMGB1 of the treatment group and the SAP group at the same time point was significantly lower than that of the control group (P0.05). The expression of TLR4 in pancreatic tissue of SAP group began to increase at 6 h, reached the peak at 12 h, and began to decrease at 24 h, which was significantly higher than that in control group at the same time point (P0.05). The TLR4 of the treatment group and the SAP group at the same time point was significantly lower than that of the control group (P0.05). Conclusion the inflammatory effect of HMGB1 in the pancreas of SAP rats may be partly combined with its receptor TLR4 and may be mediated by MyD88 dependent pathway, while ulinastatin may play a protective role by interrupting the HMGB1,TLR4 signaling pathway in the pancreatic tissue of SAP rats.
【作者单位】：四川省自贡市第一人民医院消化内科;泸州医学院附属医院消化内科;
【分类号】：R576

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