摘要
目的:观察大鼠酒精性肝病组织病理形态学改变,探讨细胞凋亡与TNF-α、Caspase-3的表达及意义。方法:采用灌胃法制备大鼠酒精性肝病(ALD)模型,模型组用40%酒精8g/(kg.d)分2次灌胃,共12周,对照组灌等量的生理盐水,实验第8、12周末分批处死动物。用HE染色观察肝脏病理学改变,用TUNEL法检测肝细胞的凋亡,用免疫组化法检测TNF-α、Caspase-3的表达。结果:模型组肝细胞凋亡明显增多,主要分布在中央静脉周围,点状、灶状坏死区;TNF-α、Caspase-3主要分布在中央静脉及肝细胞坏死灶周围细胞的胞质中,模型组TNF-α、Caspase-3表达强度明显高于对照组(P<0.05),且TNF-α的表达与Caspase-3的表达呈正相关(r=0.648,P<0.01)。结论:大鼠酒精性肝病的发生、发展过程中TNF-α、Caspase-3参与肝细胞凋亡;TNF-α通过其受体介导Caspase-3活化参与酒精性肝病的肝细胞凋亡。
Objective To observe the pathlogical changes and investigate the hepatocyte apoptosis relating with the expression of TNF -α and Caspase -3 in alcoholic liver disease （ALD） rats. Method The dose of 40% ethanol [8g/（kg · d） ） was administered intragastrically by gavage twice daily in ALD model rats for 12 weeks, the control rats were received isovolume saline by gavage. The rats were killed at the end of 8W and 12W. The pathological changes of liver was observed under light microscope after HE staining,and heaptocyte apoptosis was detected by the TUNEL method. The expression of TNF - α and Caspase - 3 in liver tissues was detected by the immunohistochemical method. Results Apoptotic hepatocytes were prominently aggregate in and around the necrotic area in model groups. The labeling index of hepatocytes apoptosis was significantly higher than that in normal control group. The positive cells of TNF - α and Caspase - 3 were observed around central vein and necrosis area in model group, and the expression intensity of the apoptosis related protein TNF -α and Caspase -3 genes was significantly higher than that of normal control group （P 〈 0. 05 ）. The expression of TNF - α had positive correlation with the Caspase - 3 （ r = 0. 648, P 〈 0. 01 ）. Conclusion TNF - α and Caspase - 3 participate in the apoptosis of hepatocytes in development and progress of ALD rats. TNF -α participates in the development of ALD by its receptor - mediated activation of Caspase -3.
出处
《吉林医学》
CAS
2009年第15期1558-1560,共3页
Jilin Medical Journal
关键词
酒精性肝病
细胞凋亡
肿瘤坏死因子-Α
半胱天冬酶-3
Alcoholic liver disease
Apoptosis
Tumor necrosis factor - α
Cystein - dependent aspartate - specefic programed - 3
