肠源性内毒素血症在非酒精性脂肪性肝炎中作用的探讨

The role of enterogenous endotoxemia in the pathogenesis of nonalcoholic steatohepatitis.

目的研究探讨肠源性内毒素血症(IETM)是导致非酒精性脂肪性肝炎早期形成阶段的重要原因。方法W istar雄性大鼠36只,随机分为3组:对照组,模型组(高脂饮食),治疗组(高脂饮食+甘氨酸),造模8周、12周时分批处死,测门静脉、腹主动脉血中内毒素(ET)水平;取肝标本做HE染色和CD14免疫组化;通过13C-美沙西丁呼气试验观察肝细胞损害程度。结果8周、12周模型组门静脉ET水平较对照组明显上升(0.62±0.11 EU/L对0.29±0.02EU/L;0.60±0.09 EU/L对0.28±0.02 EU/L,P<0.01);治疗组ET水平(0.53±0.20 EU/L和0.47±0.09 EU/L)降低,腹主动脉血ET与相对应组门静脉ET比较有显著性差异(t值分别为-7.49、12.05、-6.68和-6.07,P<0.01);13C-美沙西丁呼气试验12周模型组呼气峰值(DOB)较对照组明显升高(28.43±2.14‰对16.27±3.28‰),治疗组DOB有所下降(24.07±3.00‰),达峰时间也随之改变,与肝脏HE染色病变一致;CD14阳性细胞数随着时间的发展已明显增多。结论IETM在非酒精性脂肪性肝炎中起有重要的作用。

Objective To investigate the role of enterogenous endotoxemia in the pathogenesis of non - alcoholic steatohepatitis, Methods Thirty - six male Wistar rats were randomized into 3 groups ： normal control group, model group （ high fat diet） and treatment group （ high fat diet ± glycine）. Rats were executed at 8wk or 12 wk respectively, endotoxin levels in the portal vein and abdominal aorta were detected, The expression of CD14 in the liver was tested by irmnunohistochemical stain. The degrees of hepatic damage were determined by 13C - methacetin breath tests. Results At 8 wk and 12 wk, endotoxin levels in the portal vein of model group were significantly increased compared with control group（0. 62 ± 0.11 EU/L vs. 0.29 ± 0.02 EU/L;0.60 ± 0.09 EU/L vs. 0.28 ± 0.02 EU/L, P 〈 0.01 ）. Endotoxin levels of treatment group were decreased compared with model group（0.53 ±0.20 EU/L and 0.47 ±0.09 EU/L）. Endotoxin levels in abdominal aorta and in the portal vein of the same group were significantly different （ t = -7.49, t = 12.05, t = -6.68 andt = -6.07, respectively; P 〈 0.01 ）. 13C - methacetin breath tests at 12 wk showed that DOB of model group was sigaaificantly increased compared with control group （28.43 ± 2.14‰ vs. 16.27 ± 3.28‰,）, DOB of treatment group was decreased compared with model group （24.07 ± 3.00‰）. Time to peak also changed correspondingly and in agreement with lesions in HE stain. The number of CD14 positive cells increased significantly with time. Conclusion IETM play an important role in the pathogenesis of non - alcoholic steatohepatitis.