美沙拉嗪对肝硬化模型大鼠肠源性内毒素血症的影响

Study on Influence of Functional Improvements of Mesalazine on Intestinal Endotoxemia Model Rats with Liver Cirrhosis

目的:研究美沙拉嗪对肝硬化模型大鼠肠源性内毒素血症(IETM)的影响。方法:选择40只SPF级雄性大鼠,将其随机分为正常对照组10只、模型对照组15只和模型治疗组15只,采用四氯化碳(CCl4)符合因素法制备肝硬化大鼠模型,造模12周成功后,模型治疗组大鼠给予美沙拉嗪灌胃后4周和16周时解剖该组大鼠,取下腔静脉血测定内毒素含量,取病变肠段采用ELISA方法检测肠壁组织中TNF-α和IL-6水平,并取其肠壁组织学做病理学观察。结果:模型治疗组和正常对照组大鼠体内毒素、TNF-α和IL-6水平测得值分别为(0.17±0.05)EU/mL,(93.78±17.59)U/L,(79.01±23.47)mg/L和(0.12±0.09)EU/mL,(48.36±17.38)U/L、(51.02±22.17)mg/L低于模型对照组分别为(0.29±0.16)EU/mL,(155.25±16.10)U/L和(119.82±30.17)mg/L(P<0.05);模型治疗组大鼠体内TNF-α和IL-6水平测得值高于正常对照组(P<0.05),而内毒素水平测得值高于正常对照组,但经比较其差异无统计学意义(P>0.05);模型治疗组大鼠肝脏组织中假小叶的形成不明显,且炎性细胞浸润程度、纤维组织增生较模型对照组大鼠轻,但仍高于正常对照组,而模型治疗组大鼠肝脏细胞变性范围介于正常对照组和模型对照组之间。结论:美沙拉嗪可有效降低肝硬化模型大鼠肠源性内毒素血症血中内毒素含量和TNF-α和IL-6水平,能有效保护肠黏膜,提高肠黏膜的屏障功能。

Objective： To study the influence of functional improvements of mesalazine on intestinal endotoxemia model rats with liver cirrhosis. Methods： 40 SPF male rats were randomly divided into normal control group （n=10）, model control group （n= 15） and model treatment group （n-15）. The model of cirrhosis rat was made by CC14 coincidence factor method. After 12 weeks of model establishment, rats in model group were dissected at 4 weeks and 16 weeks after intragastric administration of mesalazine. The contents of TNF-α and IL-6 in the intestinal wall were determined by ELISA. Pathological examination was performed on the histopathology of the intestinal wall. Results： The levels of toxin, TNF-α and IL-6 in model group and normal control group were （0.17±0.05） EU/mL, （93.78± 17.59）U/L and （79.01± 23.47） mg/L, and （0.12±0.09）EU/mL, （48.36±17.38） U/L and （51.02±22.17） mg/L which were lower than those in the model control group （0.29±0.16） EU/mL and （155.25± 16.10） U/L and （119.82±30.17） mg/L respectively （P〈0.05）, The levels of TNF-α and IL-6 in the model group were higher than those in the normal control group （P〈0.05）, while the levels of endotoxin in the model group were higher than those in the nonnal control group （P〉0.05）. The model group had no obvious formation of pseudolobule in the liver tissue, and the degree of inflammatory cell infiltration and fibrosis was lighter than that of the model control group, but still higher than that of the normal control group. The model of liver cell degeneration in rats ranged from normal control group and model control group. Conclusion： Mesalazine can effectively reduce the levels of endotoxin and TNF-α and IL-6 in the blood of intestinal endotoxemia rats, by which it can effectively protect the intestinal mucosa and improve the barrier function of intestinal mucosa.