酒精性脂肪肝大鼠肠道屏障功能变化及化滞柔肝颗粒的保护作用

Changes in intestinal barrier function and protective effects of Huazhirougan granule in rats with alcoholic fatty liver disease

目的观察酒精性脂肪肝大鼠肠道屏障功能改变,并探讨化滞柔肝颗粒的保护作用。方法将60只SD大鼠随机分为正常对照组、模型组、小剂量化滞柔肝组(1.1 g·kg-1·d-1)、中剂量化滞柔肝组(2.2 g·kg-1·d-1)和大剂量化滞柔肝组(4.4 g·kg-1·d-1)。给予模型组和治疗组动物56%红星二锅头灌胃,1次/d,连续5周,制备大鼠酒精性脂肪肝模型;分别检测肠道细菌移位率(BT)和肠黏膜通透性[以乳果糖(L)/甘露醇(M)排出率(L/M%)表示]。同时观察血生化、肝脏和末段回肠黏膜病理学改变。结果在实验5 w末,模型组大鼠肝组织呈中度脂肪变和炎症改变,其BT、L/M比值、碱性磷酸酶(ALP)和肝质量指数分别为70.0%、(0.38±0.18)%、(427.1±126.6)IU/L和(4.3±0.6)%,均显著高于对照组[(分别为10.0%、(0.23±0.07)%、(306.4±67.1)IU/L和(3.6±0.4)%,P<0.05)];与模型组比,各剂量化滞柔肝颗粒处理动物肝组织小叶内炎症减轻,小剂量组L/M和肝质量指数分别为(0.27±0.06)%和(3.8±0.3)%,均低于模型组(P<0.05),肠道BT和血生化指标较模型组也有改善;中剂量和大剂量组L/M分别为(0.22±0.16)%和(0.18±0.07)%,肝质量指数分别为(3.7±0.3)%和(3.6±0.2)%,显著低于模型组(P<0.01),而肠道BT为10.0%和22.2%,ALT为(39.8±5.0)U/L和(40.8±5.6)U/L,AST为(113.4±38.3)U/L和(111.2±28.9)U/L,ALP为(334.4±47.6)IU/L和(350.2±112.2)IU/L,也均低于模型组[分别为70.0%、(54.1±17.2)U/L、(163.2±67.5)U/L、(427.1±126.1)IU/L,P<0.05)]。结论酒精性脂肪肝大鼠伴有肠道屏障功能减弱,化滞柔肝颗粒对酒精性脂肪肝大鼠肠道屏障功能及肝脏功能具有双重保护作用。

Objective To investigate the changes of intestinal barrier function and protective effects of Huazhirougan granule in rats with alcoholic fatty liver disease. Methods Sixty Sprague-Dawley （SD） rats were randomly divided into control,model,low（1.1 g·kg-1·d-1）,middle （2.2 g·kg-1·d-1） and high dose（4.4 g·kg-1·d-1） of Huazhirougan granule treatment groups;Rats in model and treatment group were fed with 56% alcohol once a day for five weeks to establish alcoholic fatty liver model,and the changes in bacterial translocation （BT）,in-testinal mucosal permeability （represented by lactulose （L）/ mannitol （M）,e.g. L/M%）,blood biochemistry,in-testinal mucosa and liver pathohistoloy were determined. Results At the end of fifth week,the changes of liver steatosis and inflammation were moderate in model rats,and the BT,L/M %,liver index and serum ALP were 70.0%,（0.38±0.18）%,（427.1±126.6）IU/L and （4.3±0.6）%,respectively,significantly higher than those in the con-trol group[10.0%,（0.23±0.07）%,（306.4±67.1）IU/L and （3.6±0.4%）,respectively,P〈0.05）];Huazhirougan treatment in the three doses significantly eased liver steatosis and inflammation; The L/M % and liver index in low dose treatment group were （0.27±0.06）% and （3.8±0.3）%,significantly lower than those in model group（P〈0.05）;The BT and liver biochemistry were also improved in the treatment group as compared to those in the control;In middle and high dose treatment group,the L/M % were（0.22±0.16）% and（0.18±0.07）%,and the liver index were （3.7±0.3）% and （3.6±0.2）%,significantly lower than those in model group（P〈0.01）;Similarly,in middle and high dose treatment group,the BT were 10.0% and 22.2%,ALT were （39.8±5.0）U/L and （40.8±5.6）U/L,AST were （113.4±38.3） U/L and（111.2±28.9） U/L,and ALP were （334.4±47.6） IU/L and （350.2±112.2） IU/L,respectively, significantly lower than those in model group [70.0%,（54.1±17.2）U/L,（163.2±67.5） U/L,（427.1±126.1）IU/L,re-spectively,P〈0.05）]. Conclusions The rats with alcoholic fatty liver disease have intestinal barrier dysfunction, and the herbal Huazhirougan granule has a protective effect on intestinal barrier and liver function.