Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis.
Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis.
复制标题
线粒体肉毒碱棕榈酰转移酶-II失活加剧大鼠肝癌发生过程中的脂质积累
DOI：
10.3748/wjg.v23.i2.256
复制
发表时间：
2017-01-14
影响因子：
4.3
通讯作者：
Yao DF
中科院分区：
文献类型：
--
作者：
Gu JJ;Yao M;Yang J;Cai Y;Zheng WJ;Wang L;Yao DB;Yao DF
目的探讨大鼠肝细胞恶性转化过程中线粒体肉毒碱棕榈酰转移酶II（CPT-II）表达的动态变化。方法雄性SD大鼠分别喂饲普通饲料、高脂饲料和高脂饲料中添加2-芴乙酰胺（2-FAA）。根据肝组织苏木精-伊红染色，将大鼠分为对照组、脂肪肝组、变性组、癌前病变组和癌变组。油红O染色观察肝脏脂质，免疫组化分析CPT-Ⅱ的变化，并与CPT-Ⅱ的特异浓度（μg/mg蛋白）进行比较。采用常规方法测定血清总胆固醇（Tch）、甘油三酯（TG）和转氨酶[丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）]水平。结果大鼠摄入HF和/或HF+2-FAA饲料后，肝脏出现大量脂质蓄积。对照组血脂水平明显低于其他各组。血清TG、Tch水平异常增高，是对照组的2-3倍（P < 0.05）。在大鼠肝脏形态学由正常向癌变发展过程中，肝细胞损伤组血清AST、ALT水平明显高于对照组（4-8倍，P < 0.05）。在肝细胞恶性转化过程中，肝组织中CPT-II的比浓度逐渐降低，癌组CPT-II的比浓度最低（P < 0.05）。结论CPT-Ⅱ低表达可能导致肝脏脂质异常蓄积，促进肝细胞恶性转化。
AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase II (CPT-II) expression during malignant transformation of rat hepatocytes. METHODS Sprague-Dawley male rats were fed with normal, high fat (HF), and HF containing 2-fluorenylacetamide (2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, precancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-II alterations were analyzed by immunohistochemistry, and compared with CPT-II specific concentration (μg/mg protein). Levels of total cholesterol (Tch), triglyceride (TG), and amino-transferases [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] were determined by the routine methods. RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls (P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher (4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-II in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-II levels in the cancer group than in any of the other groups (P < 0.05). CONCLUSION Low CPT-II expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.