摘要
目的观察长期大量饮酒对C57BL/6J乙型肝炎病毒转基因(hepatitis B virus transgenic,HBV-Tg)小鼠肝脏损伤的作用。方法将30只C57BL/6J HBV-Tg小鼠和30只同背景野生型小鼠分为4组,分别为饮取白酒的HBV-Tg酒精组、野生型酒精组、饮取水的HBV-Tg对照组及野生型对照组。连续观察18个月后,检测血清丙氨酸氨基转移酶(alanine transferase,ALT)、乙型肝炎病毒表面抗原(hepatitis B surface antigen,HBsAg)、肝组织羟脯氨酸(hydroxyproline,HYP)水平。行肝组织苏木精-伊红(hematoxylin-eosin,HE)染色、天狼星红苦味酸染色以观察肝脏形态学改变及胶原沉积情况,同时行肝组织乙型肝炎病毒核心抗原(hepatitis B core antigen,HBcAg)、HBsAg免疫组化检测HBcAg、HBsAg的表达,泛素(ubiquitin)免疫组化观察酒精性透明小体(Mallory小体)情况。结果 HBV-Tg酒精组小鼠HBsAg水平在第6个月时达峰值,随后呈下降趋势,第18个月时HBsAg水平显著低于HBV-Tg对照组(P<0.05),肝组织HBcAg、HBsAg表达显著高于HBV-Tg对照组(P<0.05)。血清ALT、肝组织HYP水平较其余3组明显增高(P<0.05),肝脏病理损伤最严重,有明显胶原沉积,未观察到肿瘤形成。Ubiquitin免疫组化Mallory小体检出率较野生型酒精组小鼠多。结论HBV表达增加酒精对肝脏损伤的程度,使肝脏更易于向纤维化方向发展。
Objective To observe the chronic ethanol consumption induced liver injury in hepatitis B virus transgen- ic （HBV-Tg） mice. Methods A total of 30 C57BL/6J HBV-Tg mice and 30 wild type （Wt） mice were divided into 4 groups. The alcohol-fed Tg mice and alcohol-fed Wt mice were fed alcohol directly in their drinking water. Control Tg mice and control Wt mice drank water only. The mice were sacrificed after 18 months and their serum were collected to detect the levels of hepatitis B surface antigen （HBsAg） and alanine transferase （ALT）. The expression level of hydroxyproline （HYP）, the histopathological changes and the hepatic collagen deposition were observed by hematoxylin-eosin （HE） and picrosirius red staining. The expressions and distributions of hepatitis B core antigen （HBcAg）, HBsAg, ubiquitin in the liver tissues were detected by immunohistochemistry. Results In the alcohol-fed HBV Tg mice, the serum level of HBsAg was increased at the sixth month, then decreased gradually, and significantly lower than that in the control Tg mice at the eighteenth month （P^0. 05）. The expressions of HBcAg and HBsAg in the liver tissues were significantly higher than those in control Tg mice. The levels of ALT in the serum, content of hydroxyproline in the liver was significantly higher than those in the other 3 groups （P^0. 05）. Severe liver injury, the hepatic collagen deposition and no evidence of tumors were observed. Mallory bodies rate was higher in alcohol-fed Tg mice than that in the alcohol-fed Wt mice. Conclusion HBV infection can increase the injury of alcohol on liver and increase the susceptibility to liver fibrosis.
出处
《华南国防医学杂志》
CAS
2013年第4期220-224,F0004,共6页
Military Medical Journal of South China
基金
国家"十二五"传染病防治科技重大专项课题(2012ZX10004503010)
