乳果糖对大鼠非酒精性脂肪性肝炎模型形成的影响

The effect of lactulose on the establishment of a rat model of non-alcoholic steatohepatitis

目的 探讨肠道环境改变与非酒精性脂肪性肝炎的关系。方法 4 2只SD大鼠随机分为模型组 (n =2 4 )、治疗组 (n =12 )和正常组 (n =6 )。模型组和治疗组大鼠以高脂饲料喂养。治疗组大鼠高脂饮食 8周后以乳果糖治疗。正常组大鼠以正常饲料喂养。实验 8周处死 12只模型组大鼠 ,16周处死模型组剩余大鼠和治疗组、正常组大鼠。测定血清转氨酶 ,HE染色观察肝脏病理改变。结果 16周模型组大鼠血清ALT、AST明显升高 ,肝脏表现为脂肪性肝炎 ,治疗组大鼠血清ALT、AST明显下降 ,接近正常组水平 ,肝组织炎症活动计数也明显下降 (5 .83± 2 .0 2比 3.6 3± 0 .6 4 ) ,但仍显著高于 8周模型组大鼠水平 (3.6 3± 0 .6 4比 1.98± 0 .90 )。治疗组肝细胞脂肪变性程度无显著变化。结论 乳果糖可以改善高脂饮食诱发的脂肪性肝炎大鼠肝组织炎症损伤 ,但不能完全阻止炎症的进展 。

Objective To explore the relationship between the change of intestinal environment and pathogenesis of non alcoholic steatohepatitis (NASH). Methods Forty two SD rats were divided into 3 groups randomly: model group( n =24), treatment group( n =12) and normal group( n =6). The rats of model group and treatment group were given fat rich diet, and those of normal group were given normal diet. Furthermore, the rats of treatment group were given lactulose after 8 weeks of fat rich diet feeding. Twelve rats of model group were sacrificed at 8 weeks of study. At 16 weeks, the rats of treatment group, normal group, and the rest of model group were sacrificed. The serum levels of aminotransferase were measured and the pathology of livers were observed by HE stain. Results The rats' livers presented the pathology of steatohepatitis with higher serum levels of ALT and AST in the 16 weeks model group. The serum levels of ALT and AST of treatment group decreased significantly and were close to normal group. The hepatic inflammation scores also decreased markedly (5.83±2.02 vs. 3.63±0.64), but were still higher (3.63±0.64 vs. 1.98 ±0.90) than those of 8 weeks model group. And the degree of hepatocyte steatosis did not change in the treatment group. Conclusions Lactulose could ameliorate the hepatic inflammation of rats with steatohepatitis induced by fat rich diet, but could not prevent the development of steatohepatitis. It suggested the change of intestinal environment, such as intestinal bacteria overgrowth, was one of important factors in the pathogenesis of NASH.