壳脂胶囊对慢性乙型肝炎合并非酒精性脂肪性肝炎鸭抗病毒治疗应答的影响

Effect of Kezhi capsula on anti-viral response to HBV infection in duck with NASH

目的:观察中药壳脂胶囊对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝炎(NASH)鸭抗病毒治疗应答的影响。方法:采用先天感染DHBV(鸭乙肝病毒)的广东麻鸭并高糖高脂饲料填饲,建立鸭乙型肝炎合并NASH模型。实验共分为9组,模型组:恩替卡韦+壳脂胶囊高(M1)、中(M2)、低剂量组(M3),壳脂胶囊高(M4)、中(M5)、低剂量组(M6)及恩替卡韦模型组(M7);对照组:病毒对照组(D1),恩替卡韦对照组(D2)。模型组分别采用恩替卡韦+壳脂胶囊、单用壳脂胶囊和单用恩替卡韦治疗,对照组分别用生理盐水和恩替卡韦治疗,治疗21天。分别于治疗前(T0)、治疗21天(T21)检测鸭血清ALT、AST、γ-GT、ALP等肝功能指标以及TC、TG、HDL-C、LDL-C、Glu等糖脂代谢指标,荧光定量PCR检测鸭血清DHBV DNA;检测鸭肝内TC、TG和肝组织内DHBVDNA以及肝组织病理学检查。结果:治疗后恩替卡韦+壳脂胶囊组(M1、M2、M3)与恩替卡韦模型组(M7)比较,无论血清DHBV DNA还是肝内DHBV DNA差异均有显著性意义(P<0.05或P<0.01);恩替卡韦对照组(D2)与恩替卡韦模型组(M7)比较,抗病毒效果差异有显著性意义(P<0.01);肝脏组织病理学检查显示,恩替卡韦联合壳脂胶囊抗病毒、降脂治疗后,鸭肝脏炎症及脂肪变程度较病毒对照组明显减轻。结论:壳脂胶囊/CHB合并NASH鸭治疗后能改善肝脂肪变,提高其抗病毒应答率。

Objective： To assess the effect of lipid lowering therapy with traditional Chinese medicine and anti - viral therapy on hepatitis B viral （HBV） DNA level in the treatment of non- alcoholic steatohepatitis （NASH） secondary to chronic hepatitis B （CHB） . Methods： Congenital infection of duck HBV （DHBV） were screened by a high- glucose and high -fat diet to estab- lish the model of NASH in CHB, and were divided into 9 groups. Animals in the NASH model groups were treated with entecavir combined with Kezhi capsula, Kezhi capsula alone or entecavir alone, while physiological saline or entecavir was administered to the ducks in the control groups. The duration of treatment was 21 days for all groups. Liver function indices were examined, in- cluding ALT, AST, γ- GT, and ALP, and as were indices of glucose and lipid metabolism including TC, TG, HDL - C and LDL- C, and fasting blood glucose levels. Serum samples were tested prior to treatment （TO） , 21 （T21） post -treatment. The serum and intrahepatic DHBV DNA level were determined using quantitative fluorescent PCR. Results： There were signifi- cant differences in both serum and intrahepatic DHBV DNA level between the groups that received entecavir and Kezhi capsula and the NASH control group that received entecavir alone. The serum DHBV DNA load was significantly reduced in the anti - vi- ral treatment groups compared with the untreated groups. There was also a significant difference in the anti - viral efficacy be-tween the control NASH group treated with entecavir and the normal diet control group treated with entecavir. Pathological exami- nation of hepatic tissues showed that following anti - viral and lipid - lowering therapy with entecavir combined with Kezhi cap- sules, the liver inflammation and hepatic steatosis were significantly reduced compared to the untreated control group. Cortelusion： Hepatic steatosis in CHB affects the anti - viral efficacy of nucleoside analogues. Lipid lowering therapy with traditional Chinese medicine improves hepatic steatosis and increases the response to anti -viral treatment.