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Bcl-2、NF-kB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)分二次灌胃共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染色及天狼星红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Bcl-2、NF-kB的表达。结果①模型组与对照组比较,肝细胞明显肿胀,可见大小不等的脂肪空泡,部分处可见点状、灶壮坏死,肝组织内胶原纤维轻度增生,随造模时间延长模型组病变加重。②凋亡的肝细胞主要位于肝组织中点状、灶状和碎屑样坏死区及其周围,模型组肝细胞凋亡指数明显高于对照组(P<0.05)。③Bcl-2和NF-kB阳性细胞主要分布在中央静脉及肝细胞坏死灶周围,模型组Bcl-2、NF-kB表达强度明显高于对照组(P<0.05)。④Bcl-2和NF-kB表达间存在相关性,且两者之间存在正相关关系(r=0.576,P<0.01)。结论大鼠酒精性肝病发生与肝细胞凋亡密切相关。大鼠酒精性肝病的发生、发展过程中Bcl-2和NF-kB参与肝细胞凋亡。NF-kB基因活化后,上调Bcl-2基因的表达。
[Objective] To observe the pathological changes and investigate the hepatoeyte apoptosis relating with Bcl-2 and NF-kB in alcoholic liver disease （ALD） of rats. [Method] The dose of 40% ethanol 8 g/（kg·d）, was administered intragastrieally by gavage twice daily in ALD model rats for 12 weeks, the control rats were received isovolume saline by gavage. Rats were killed at the end of 8 W, 12 W. The pathological changes of liver was observed under light microscope after H-E and Sirius-red staining,and heap toeyte apoptosis was detected by the TUNEL method. The expression of Bcl-2 and NF-kB protein in liver tissues was detected by the immune- ohistochemical method. [Results] Compared with that in the control group, the hepatoeytes became swelling and macro and mierovesieular steatosis, spotty and focal necros is, inflammation were observed in model group, and pathological changes was gradually progression. Apoptotie hepatocytes were prominently aggregate in and around of the necrotic area in model groups. The labeling index of hepatocytes apoptosis was significantly higher than in normal control group （P 〈0.05）. The positive cells of Bel-2 and NF-kB were observed around central vein and necrosis area in model group, and the expression intensity of the apoptosis related protein Bel-2 and NF-kB genes was significantly higher than that of normal control group （P 〈0.05）. There was a positive correlation between the expression of Bel-2 and NF-kB （r =0.576, P 〈0.01）. [Conclusion] Occurrence of alcoholic liver disease was closely associated with heap tocytes apoptosis. The Bcl-2 and NF-kB partaked in occurrence and progress of alcoholic liver disease. Upregulated the Bcl-2 gene expression after NF-kB activation. Occurrence of alcoholic liver disease was closely associat- ed with heaptoeytes apoptosis. The Bcl-2 and NF-kB partaked in occurrence and progress of alcoholic liver disease. Upregulated the Bcl-2 gene expression after NF-kB activation.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2009年第1期55-58,63,共5页
China Journal of Modern Medicine
基金
吉林省教育厅科技计划项目:吉教科合字[2007]第自9号
关键词
酒精性肝病
细胞凋亡
B细胞淋巴瘤-2基因
核转录因子-KB
alcoholic liver disease（ALD）
apoptosis
bcell lymphoma/leukemia-2 gene （Bcl-2）
nuclear transcription factor-KappaB （NF-kB）
