大鼠酒精性肝损伤与肠内毒素渗漏的关系及健脾理气活血方的干预作用

目的 从酒精性肝损伤与小肠通透性改变、内毒素渗漏的病理联系，探讨健脾理气活血中药复方抗酒精性肝损伤的作用和机理。方法 复制Lieber-DeCarli酒精性肝损伤模型。42只雄性SD大鼠随机分设正常组（n：6）、无酒精液体饲料组（对照组，n=12）、酒精液体饲料组（模型组，n=12）及酒精液体饲料＋中药组（中药组，n=12）。在造模第3周开始灌胃给药或蒸馏水直至6周末。禁食5h后，各组复以10mg／kg的内毒素（LPS）灌胃，并在灌胃3．5h后取其门静脉血浆和下腔静脉血清及肝肠组织，观察：（1）通过门脉血浆内毒素含量测定判断小肠通透性变化；（2）小肠HE染色病理变化及其超微结构变化；（3）肝组织病理变化；肝组织TG含量，血清ALT活性变化；（4）血浆TNF-α含量的变化。结果（1）模型组肝组织脂肪变性明显。肝脏TG含量大幅度提高；同时血清ALT活性及血浆TNF-α含量显著升高。（2）模型组血浆内毒素水平显著高于正常组和对照组，提示肠通透性增加；同时，可见小肠黏膜微绒毛的明显损伤。（3）较之模型组。中药组的上述指标均有显著改善。（4）血浆TNF-α含量与内毒素水平及血清ALT活性均呈显著正相关。结论 健脾理气活血中药可以抑制酒精引起的肠通透性增加，减轻内毒素渗漏，从而减轻肝损伤。

Relationship between Alcoholic Liver Injury and Endotoxin Leakage from Gut and Intervention Effect of Jianpi Liqi Huoxue Decoction

OBJECTIVE: To study the effects and mechanisms of Jianpi Liqi Huoxue Decoction (JLHD) in anti-alcoholic liver injury (ALI) through the pathological relation of ALI with changes of intestinal permeability and endotoxin leakage. METHODS: The liver injury model induced by Lieber-DeCarli alcoholic forage was established. Altogether 42 male SD rats were randomly divided into 4 groups, the normal group (n=6), the control group fed with non-alcohol diet (n=12), the model group fed with alcoholic diet (n=12) and the treated group fed with alcoholic diet and treated with JLHD (n=12). The medicine or distilled water was administered by gavage from the 3rd week to the end of the 6th week. Then after fasting for 5 h all the rats except those in the normal group were given lipopolysaccharide (LPS) 10 mg/kg by gavage, and the blood plasma from portal vein, serum from inferior cava vein as well as tissues of liver and intestine were prepared for detection of plasma LPS level in the portal vein to observe the change of intestinal permeability through LPS content in portal vein blood plasma, the pathological and ultrastructural changes of the small intestine by HE staining, the pathological change of liver and triglyceride (TG) content and gamma glutamyl transpeptidase (GGT) activity in liver, the changes of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, and plasma tumor necrosis factor-alpha (TNF-alpha) level. RESULTS: In rats after modeling, there were obvious fatty degeneration, significant increase of hepatic TG content and GGT activity, serum ALT and AST activity, as well as plasma TNF-alpha level, with high plasma LPS level indicating increased intestinal permeability, and seriously injured mucosa microvilla of small intestine. However, all the above abnormal changes were milder in the treated group than those in the model group. Meanwhile, the TNF-alpha content, endotoxin level and ALT activity were found to be positively correlated. CONCLUSION: JLHD could alleviate liver injury through inhibiting the alcohol induced increased intestinal permeability and lessening endotoxin leakage.