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目的 观察肝细胞恶性转化过程中线粒体内膜肉毒碱棕榈酰基转移酶Ⅱ (CPT-Ⅱ)的动态改变.方法 雄性SD大鼠分为对照组、脂肪肝组和诱癌组,分别以常规,高脂及含二乙基氨基芴(2-FAA)高脂饲料喂饲共14周.每2周处死对照鼠1只、脂肪肝和诱癌鼠各1组,留肝组织和血液.肝组织按HE检查结果分为对照组、脂肪肝组、变性组、癌前组和癌变组.肝脂质以油红O染色,肝CPT-Ⅱ表达以免疫组织化学法分析,以比浓度法比较组间肝CPT-Ⅱ浓度,并定量血清总胆固醇、甘油三酯(TG)、丙氨酸氨基转移酶、天冬氨酸氨基转移酶水平.组间比较用t检验. 结果 摄人脂肪后SD鼠肝细胞见大量脂肪积聚,正常对照组脂肪含量明显低于脂肪肝(t=-11.556,P＜ 0.001)、变性组(t=-4.847,P=0.04)、癌前病变(t=-13,652,P=0.005)和癌变组(t=-10.896,P=0.008).肝细胞变性、癌前病变和癌变组血清TG,血清总胆固醇水平明显高于正常对照组(P＜0.05),TG和血清总胆固醇升高2～3倍.经2-FAA诱癌后肝细胞形态学表现为肝细胞发生变性、癌前病变和癌变的发展过程,伴有肝细胞损伤,肝细胞变性、癌前病变和癌变组天冬氨酸氨基转移酶及丙氨酸氨基转移酶活性显著高于正常对照组的4～8倍(P＜0.05).定量肝CPT-Ⅱ比浓度并经免疫组织化学证实,在肝细胞癌变期间显著低于对照和脂肪肝组(P＜ 0.05).结论 CPT-Ⅱ酶低表达或功能丧失致肝细胞脂肪积聚加重,对肝细胞恶性转化过程起促进作用.“,”Objective To investigate the dynamic expression of hepatic carnitine palmitoyltransferase-Ⅱ (CPT-Ⅱ) in the mitochondrial inner membrane during hepatocyte malignant transformation induced by lipid accumulation.Methods Male Sprague-Dawley rats were divided randomly into control,fatty liver,and induced cancer groups,which were fed with normal,high-fat (HF),and HF containing 2-fluorenylacetamide (0.05％,2-FAA) diets,respectively,for 14 weeks.One rat from each group was sacrificed every two weeks and the blood and liver samples were collected.Liver morphological changes were evaluated with hematoxylin and eosin staining,and the liver tissue samples were divided into control,fatty liver,degeneration,precancerous,and cancerous groups accordingly.Hepatic lipids were dyed by the oil red O method.The CPT-Ⅱ expression was measured by immunohistochemistry and compared with the specific CPT-Ⅱ concentration (ng/mg liver protein,ng/mg P) among different groups.Serum levels of circulating total cholesterol (Tch),triglyceride (TG),alanine aminotransferase (ALT),and aspartate aminotransferase (AST) were quantitatively analyzed.Results Massive lipid accumulation hepatocytes was seen in rats on HF and HF containing 2-FAA diets.The lipid levels in the control group were significantly lower than those in the fatty liver (t =-11.556,P ＜ 0.001),degeneration (t =-4.847,P =0.04),precancerous (t =-13.652,P =0.005),and cancerous groups (t =-10.896,P =0.008).The serum TG and Tch levels in the degeneration,precancerous,and cancerous groups were 2-3 times higher than those in the control group (P ＜ 0.05).After 2-FAA treatment,the morphological changes of rat hepatocytes showed the progression from degeneration and precancerosis to cancerosis,with hepatocyte injury.The serum AST and ALT levels in the degeneration,precancerous,and cancerous groups were significantly higher (4-8times) than those in the control group (P ＜ 0.05).The specific concentration of liver CPT-Ⅱ expression was significantly reduced during hepatocyte malignant transformation,as confirmed by immunohistochemistry,with the CPT-Ⅱ levels significantly lower in the cancerous group than in any of other groups (P ＜ 0.05).Conclusion Low hepatic CPT-Ⅱ expression might lead to abnormal lipid accumulation in hepatocytes,which should promote the malignant transformation of hepatocytes.