TAA诱导的A型肝性脑病大鼠肠道通透性改变及机制研究  

Intestinal Permeability in TAA-induced Acute HE Rats

作　　者：郑鋆 Zheng Yun(Xiamen Branch,Zhongshan Hospital,Fudan University,Fujian,Xiamen,361006)

机构地区：[1]复旦大学附属中山医院厦门医院,福建厦门361006

出　　处：《辽宁医学杂志》2021年第5期1-5,共5页Medical Journal of Liaoning

基　　金：厦门市科技计划(医疗卫生项目);项目编号:3502Z20184008。

摘　　要：目的研究TAA法诱导的A型肝性脑病大鼠肠道通透性改变及其机制。方法于2020年12月至2021年3月选取雄性SD大鼠共30只随机分组,正常对照组8只腹腔注射生理盐水,肝性脑病模型组22只腹腔注射TAA(300mg/kg连续3天每隔24h),造模成功后根据肝性脑病临床分级将肝性脑病组进一步细分为低级别肝性脑病组和高级别肝性脑病组,记录造模结束三组实验鼠的体重变化;处死后取空肠进行离体肠道通透性测定;干湿重法比较肠壁水肿程度;RT-PCR法测定肠道紧密连接蛋白ZO-1、Occludin及炎症因子TNF-α的表达水平。结果模型组共获得低级别肝性脑病大鼠和高级别肝性脑病大鼠各8只,死亡6只;肝性脑病组较正常对照组体重下降(0.06±0.04 VS-0.07±-0.02 VS-0.17±0.03,P<0.05),单位面积离体肠道通透性增加(0.82±0.11 VS 1.36±0.30 VS 1.74±0.32,P<0.05),肠壁明显水肿(3.02±0.18 VS 3.57±0.22 VS 4.44±0.43,P<0.05),具有统计学差异;且高级别肝性脑病组较低级别肝性脑病组变化趋势更为显著;肠道紧密连接蛋白ZO-1、Occludin表达存在下降趋势,但无统计学差异;炎症因子TNF-α表达升高(0.03±0.01VS 0.04±0.01 VS 0.08±0.02,P<0.05),存在统计学差异。结论 TAA诱导的A型肝性脑病大鼠肠道通透性与正常对照组相比显著增加,且肠道屏障破坏程度与肝性脑病临床分级存在相关,推测其机制可能与炎症因子TNF-α的表达升高有关。Objective To investigate the change of intestinal permeabilty and its underlying mechanisms in TAA-induced acute HE rats.Methods The studies were conducted on male Sprague-Dawley rats from December 2020 to March 2021.30 rats were randomly divided into control group and HE group.8 control rats received sodium saline solution.22 HE model was induced by intraperitoneal injection of TAA 300 mg/kg every 24 hours for 3 days.Body weight and encephalopathy grade of each rat was assessed, and then the HE group was further divided into low-grade HE group and high-grade HE group according to the clinical manifestation of HE.The intestinal barrier integrity of jejunum was evaluated by FITC-dextran, edema of jejunum was assessed by wet-to-dry weight ratio, gene expression levels of tight junction protein ZO-1 and Occludin, inflammatory factor TNF-α in jejunum tissues were analyzed by RT-PCR respectively.Results In the model group, 8 rats with low-grade HE and 8 rats with high-grade HE were obtained, and 6 rats died.HE rats lost weight(0.06±0.04 VS-0.07±-0.02 VS-0.17±0.03,P<0.05),had increased intestinal permeability(0.82±0.11 VS 1.36±0.30 VS 1.74±0.32,P<0.05)and more edematous bowel wall(3.02±0.18 VS 3.57±0.22 VS 4.44±0.43,P<0.05)compared to the rats in the control group.Moreover, the change trend of high-grade HE group was more significant than that of low-grade HE group.The gene expression level of ZO-1 and Occludin were decreased in HE group, but the differences between two groups were not statistically significant.While the level of TNF-α was increased in HE group with statistical difference(0.03±0.01 VS 0.04±0.01 VS 0.08±0.02,P<0.05).Conclusion Compared with the control group, the intestinal permeability of TAA-induced acute HE rats was significantly increased, and the degree of intestinal barrier damage was related to the clinical grade of HE.It is speculated that the underlying mechanism may be related to the increased expression of inflammatory factor TNF-α.

关 键 词：TAA 肝性脑病 肠道通透性 紧密连接蛋白 TNF-α 

分 类 号：R575.5[医药卫生—消化系统]