大黄素通过影响AQP3表达水平改善急性重症胰腺炎大鼠的器官功能-东南大学学报医学版

大黄素通过影响AQP3表达水平改善急性重症胰腺炎大鼠的器官功能

单位：1. 四川省人民医院急诊科, 四川成都 610072;
2. 四川省人民医院急诊外科, 四川成都 610072;
3. 四川省人民医院肝胆外科, 四川成都 610072

分类号：R576;R282.710.7

出版年·卷·期（页码）：2017·36·第四期（574-580）

摘要：

目的：探讨大黄素对急性重症胰腺炎（SAP）大鼠器官功能及水通道蛋白3（AQP3）信号通路的影响。方法：将72只大鼠随机分为假手术组（Sham组，24只）、模型组（Model组，24只）和大黄素组（Emodin组，24只）。Model组和Emodin组通过胰管内注射牛黄胆酸钠的方法建立SAP大鼠模型，Sham组仅向胰管内注射等量生理盐水。Emodin组采用大黄素灌胃，Sham、Model组给予等量生理盐水。造模后24、48、72 h每组分别处死8只大鼠，取其组织，石蜡包埋切片后经苏木精-伊红（HE）染色后光镜下观察大鼠胰腺、肝脏、肺脏组织病理改变，采用酶联免疫吸附试验（ELISA）检测各组大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平含量，氯化硝基苯-α-半乳糖麦芽糖苷法检测血清淀粉酶（Amy）的含量，蛋白质免疫印迹法（Western blotting）检测回肠中AQP3蛋白表达，实时荧光定量PCR（RT-qPCR）检测回肠中AQP3的mRNA表达。结果：Sham组不同时间点胰腺、肝脏、肺脏病理评分均显著低于Emodin组和Model组（均P<0.05），Emodin组不同时间点胰腺、肝脏、肺脏病理评分均显著低于Model组（均P<0.05）。Sham组不同时间点血清Amy、TNF-α、IL-6水平均显著低于Emodin组和Model组（均P<0.05），Emodin组不同时间点血清Amy、TNF-α、IL-6水平均显著低于Model组（均P<0.05）。Sham组回肠中不同时间点AQP3蛋白及mRNA表达均显著低于Emodin组和Model组（均P<0.05），Emodin组回肠中不同时间点AQP3蛋白及mRNA表达均显著低于Model组（均P<0.05）。结论：SAP病理改变与AQP3异常表达有关；大黄素能够保护SAP的器官功能，降低炎症因子释放，其作用机制可能与下调AQP3表达、降低肠黏膜通透性有关。

Objective:To investigate the organ function and AQP3 signal pathway effect of emodin on severe acute pancreatitis rats. Methods:A total of 72 rats accorded to the random number table method was divided into sham operation group (Sham group) of 24 rats, Model group of 24 rats and Emodin group of 24 rats, SAP model was established in the Emodin group and the Model group, same volume of normal saline was intraperitoneal injected into the pancreatic duct in the Sham group. The Emodin group was orally administered emodin, the Sham group and the Model group were given the same amount of normal saline. After 24 h, 48 h and 72 h of model establishment, 8 rats was sacrificed in each group, the pathological changes of pancreas, liver and lung were observed under electron microscope, serum TNF-α, IL-6 level was detected by enzyme-linked immunosorbent test, serum Amy level was detected by chlorinated nitrobenzene alpha galactose method, ileal AQP3 protein expression level was detected by Western blotting, ileum AQP3 mRNA expression level was detected by quantitative real-time PCR. Results:24 h, 48 h, 72 h after model establishment, pancreas, liver, lung tissue had significantly pathological changes in the three groups. After 24 h, 48 h, 72 h, histopathological score in the Emodin group showed a significant decreased trend (P<0.05). The pathological scores of the pancreas, liver, lung in the Sham group at different time points were significantly lower than those of the Emodin group and the Model group (P<0.05), moreover those of the Emodin group at different time points were significantly lower than those of the Model group (P<0.05).After 24 h, 48 h, 72 h, serum Amy,TNF-α,IL-6 level in the Emodin group showed a significant decreased trend (P<0.05),those of the Sham group at different time points were significantly lower than those of the Emodin group and the Model group (P<0.05), those of the Emodin group at different time points were significantly lower than those of the Model group (P<0.05). After 24 h, 48 h, 72 h, AQP3 protein and mRNA in the Emodin group showed a significant decreased trend (P<0.05), AQP3 protein and mRNA in the Sham group at different time points were significantly lower than those of in the Emodin group and the Model group (P<0.05), with the former lower than the latter (P<0.05). Conclusion:The abnormal expression of AQP3 is related to SAP, emodin can protect the organ function of SAP and reduce the release of inflammatory factors, and its mechanism may be related to the down-regulation of AQP3 expression and decrease intestinal permeability.

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