Objective To evaluate the effect of anti-histamine treatment on intestinal endotoxemia and liver inflammation in experimental chronic hepatitis rats.Methods Thirty Wistar rats (15 males and 15 females) were randomly divided into control group (n =8),chronic hepatitis group (n =12) and hepatitis + anti-histamine group (n =10).Chronic hepatitis was induced by subcutaneous injection with 40％ of CCl4,and feeding with low protein,low choline,high cholesterol and high alcohol diet.Antihistamine treatment was given 1 week after the modeling by intragastric administration of ketotifen (1.25 mg/kg).All rats were sacrificed 4 weeks later.Plasma endotoxin,alanine aminotransferase (ALT),total bilirubin (TBil),tryptase,histamine,interferon-γ (IFNγ),iuterleukin (IL)-12,IL-10 and IL-4levels were detected,and the changes in liver histology,the morphology and ultrastructure of mast cells were observed.SPSS 13.0 software package was used for statistical analysis.ANOVA was used for the comparison of measurement data,and SNK method was used for pairwise comparison.Results Plasma endotoxin,ALT,TBil,tryptase,plasma and liver tissue histamine concentrations were (81 ± 19) pg/mL,(186 ± 140) U/L,(10.2±6.2) μmol/L,(0.75 ±0.21) mg/mL,(145 ±52) ng/mL,and (107 ±43) ng/100 mg in chronic hepatitis group,while the above parameters were significantly lower in anti-histamine group except TBil (P ＜ 0.05).Under light microscope,fatty degeneration and fibrosis were formed in liver of chronic hepatitis rats,the hepatic injury was attenuated in anti-histamine group.Toluidine blue stain showed that there was many degranulating and degranulated mast cells filled with purple granula around liver blood vessels and in fiber-interval in chronic hepatitis group,and there were few purple granula in anti-histamine group.The number of mast cells in anti-histamine group was (6.5 ± 1.5)/HP,which was significantly lower than chronic hepatitis group [(10.9 ± 1.6)/HP,P =0.000],but was still higher than that in the control group [(2.2 ± 0.9)/HP,P =0.000].Under electron microscope,the phenomenon of degranulation was severe in chronic hepatitis group and moderate in the anti-histamine group.Compared with the chronic hepatitis group,IL-4 and IL-10 in anti-histamine group were significantly decreased (P ＜0.05),IL-12 was increased (P ＜0.05),but the level of IFN-γ had no significant change (P ＞ 0.05).Conclusion Anti-histamine therapy can significantly improve liver inflammation and alleviate intestinal endotoxemia.%目的 研究抗组胺治疗对实验性肝炎大鼠肠源性内毒素血症(IETM)和肝脏炎症的影响.方法 取Wistar大鼠30只(雌雄各15只),按数字表法随机分为健康对照组8只、慢性肝炎组12只和抗组胺治疗组10只.慢性肝炎组和抗组胺治疗组采用40％四氯化碳溶液皮下注射,同时辅以低蛋白、低胆碱、高脂肪、高醇饮食,抗组胺治疗组在造模成功(一周)后用酮替芬(1.25 mg/kg体质量)抗组胺治疗.4周末处死动物,取血分别检测血浆内毒素、血清丙氨酸转氨酶(ALT)、总胆红素(TBil)、类胰蛋白酶、组胺、干扰素γ(IFNγ)、白介素(IL)-12、IL-10与IL-4水平,同时观察肝脏组织学变化及肥大细胞的形态和超微结构改变.应用SPSS13.0软件包进行统计学分析,计量资料多组间比较采用单因素方差分析,两两比较采用SNK法.结果 慢性肝炎组血浆内毒素、ALT、TBil、类胰蛋白酶、血浆和肝组织中的组胺浓度分别为(81±19) pg/mL,(186±140) U/L,(10.2±6.2) μmol/L,(0.75±0.21)mg/mL,(145±52) ng/mL和(107±43) ng/100 mg,抗组胺治疗组上述指标明显降低,除TBil外,其余指标与慢性肝炎组比较差异均有统计学意义(P＜0.05).光镜下,慢性肝炎组有脂肪变性和纤维化形成,而抗组胺治疗组肝损伤明显减轻；甲苯胺蓝染色可见慢性肝炎组肝脏血管周围及纤维间隔内大量正在脱颗粒和已经脱颗粒并充满紫色颗粒的肥大细胞,而抗组胺治疗组仅见细胞质中充有少量紫色颗粒.慢性肝炎组肥大细胞的数量为(10.9±1.6)个/HP,而抗组胺治疗组为(6.5±1.5)个/HP,两组差异有统计学意义(P =0.000),但仍高于健康对照组[(2.2±0.9)个/HP,P=0.000].电镜下,慢性肝炎组肥大细胞明显脱颗粒,抗组胺治疗后脱颗粒减少.与慢性肝炎组比较,抗组胺治疗组的IL-4和IL-10水平较慢性肝炎组明显降低(P＜0.05),IL-12水平明显升高(P＜0.05),IFNγ水平变化不明显(P＞0.05).结论 抗组胺治疗可以明显改善肝脏炎症并减轻肠源性内毒素血症.
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