Jin Wu-pi, Quan Xiu-quan, Meng Fan-ping, Cui Xiang-dan, Piao Hai-jin
Affiliated Hospital of Yanbian University, Yanji 133000, Jilin, China.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2007 Jul;19(7):419-21.
To observe the pathological changes and investigate the correlation of hepatocyte apoptosis with cytochrome P450 2E1(CYP2E1) expression and oxygen free radical in alcoholic liver disease (ALD) in rat.
40% ethanol in the dose of 8 g/kg body weight was given to rats by gavage twice daily for 8 weeks in model group (n=37), and rats in control group (n=33) received same volume of saline by gavage. At the end of the 8th week, the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The pathological changes in the liver was observed under light microscope with hematoxylin and eosin (HE) staining, and hepatocyte apoptosis was detected by the terminal deoxynucleotidyl transferase mediated dUTP biotin nick and labeling (TUNEL) method. Expression of serum CYP2E1 was determined by polymerase chain reaction (PCR), the contents of malondialdehyde (MDA) and activities of superoxide dismutase (SOD) in serum were detected by thibabituric acid (TBA) quantifying method.
The TUNEL positive cells were located around the central vein, and spotty and focal necrosis was found in the ALD group. The apoptotic index (AI) in the ALD group was significantly higher than in the control group (P<0.05). To express in CYP2E1, the allelic frequency of c1 and c2 were 91.65%, and 8.35% respectively, in control group, while the allelic frequency of c1 and c2 were 53.35% and 46.65%, respectively, in ALD group, and there were significantly differences between two groups (all P<0.05). The content of MDA in serum had positive correlation with hepatocyte apoptosis index (MDA vs. AI, r( MDA ) =0.644), and the activity of SOD in serum had negative correlation with AI (SOD vs. AI, r( SOD ) =-0.511, all P<0.05) in the ALD group, and there was negative correlation between MDA and SOD (r=-0.582, P<0.05).
Chronic alcohol administration induced alcoholic liver disease and liver dysfunction, and hepatocyte apoptosis is enhanced. Rsa I and Pst I RFLPs are related with ALD in model rats, and c2 gene might be related with the development of ALD. The content of MDA and activity of SOD play an important role in the process of hepatocyte apoptosis and lipid peroxidation process.
观察酒精性肝病（ALD）大鼠肝脏的病理变化，探讨肝细胞凋亡与细胞色素P450 2E1（CYP2E1）表达及氧自由基的相关性。
模型组（n = 37）大鼠每日两次经口灌胃给予40%乙醇，剂量为8 g/kg体重，共8周；对照组（n = 33）大鼠经口灌胃给予等量生理盐水。第8周结束时，测定血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）含量。采用苏木精-伊红（HE）染色，在光学显微镜下观察肝脏病理变化，采用末端脱氧核苷酸转移酶介导的dUTP生物素缺口末端标记（TUNEL）法检测肝细胞凋亡。采用聚合酶链反应（PCR）检测血清CYP2E1表达，采用硫代巴比妥酸（TBA）定量法检测血清丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性。
TUNEL阳性细胞位于中央静脉周围，ALD组可见点状及灶状坏死。ALD组凋亡指数（AI）显著高于对照组（P < 0.05）。对照组CYP2E1中c1和c2等位基因频率分别为91.65%和8.35%，ALD组c1和c2等位基因频率分别为53.35%和46.65%，两组间差异有统计学意义（均P < 0.05）。ALD组血清MDA含量与肝细胞凋亡指数呈正相关（MDA与AI，r（MDA） = 0.644），血清SOD活性与AI呈负相关（SOD与AI，r（SOD） = -0.511，均P < 0.05），且MDA与SOD呈负相关（r = -0.582，P < 0.05）。
长期酒精摄入可诱发酒精性肝病及肝功能损害，肝细胞凋亡增强。Rsa I和Pst I限制性片段长度多态性（RFLPs）与模型大鼠ALD有关，c2基因可能与ALD的发生发展有关。MDA含量和SOD活性在肝细胞凋亡及脂质过氧化过程中起重要作用。
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