[1]康敏,李森,钟德君,等.非酒精性脂肪肝大鼠肝细胞凋亡与线粒体膜通透性转换孔开放的关系[J].南方医科大学学报,2013,(07):1062.
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非酒精性脂肪肝大鼠肝细胞凋亡与线粒体膜通透性转换孔开放的关系()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2013年07期
页码:
1062
栏目:
出版日期:
2013-07-15

文章信息/Info

Title:
Hepatocyte apoptosis and mitochondrial permeability transition pore opening in rats with nonalcoholic fatty liver
作者:
康敏李森钟德君杨志敏李鹏
关键词:
非酒精性脂肪肝凋亡线粒体细胞膜通透性Bcl-2/Bax
Keywords:
nonalcoholic fatty liver apoptosis mitochondria membrane permeability Bcl-2/Bax
摘要:
目的通过研究肝细胞凋亡及线粒体膜通透性转换孔(MPTP)开放在大鼠非酒精性脂肪性肝病(NAFLD)形成中的作用,
探讨NAFLD的发病机理。方法30只雄性SD大鼠随机分为正常对照组和高脂饲料4、8、12周组;流式细胞仪检测肝细胞凋亡;
紫外分光光度计检测MPTP开放程度;免疫组织化学法检查Bcl-2、Bax在肝组织中表达情况;Western Blot检测肝脏Bax表达及
变化情况。结果与正常对照组比较,高脂4~12周组肝细胞凋亡指数增加;紫外分光光度计检测显示高脂组随着造模时间延
长,MPTP开放增加;免疫组化显示Bcl-2在4、8、12周高脂组表达,但组间比较阳性细胞数增加不明显;Bax在高脂组随造模时
间延长阳性细胞数增加;Western Blot 进一步证实Bax 在高脂组随造模时间延长蛋白表达量增加;并且随着脂肪肝的进展,
Bcl-2/Bax 比率进行性下降。结论NAFLD大鼠模型中存在肝细胞凋亡,线粒体损伤与肝细胞凋亡密切相关,MPTP开放是
NAFLD大鼠重要线粒体损伤机制,而Bax表达量增加、Bcl-2/Bax比率异常是MPTP开放的分子基础。
Abstract:
Objective To investigate the role of hepatocye apoptosis and mitochondrial permeability transition pore (MPTP)
opening in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Methods Thirty male SD rats were randomized into
normal diet group and high-fat diet group. At 4, 8 and 12 week of feeding. The hepatocyte apoptosis index (AI) was measured
using flow cytometry, and MPTP opening was evaluated with ultraviolet spectrophotometry. Immunohistochemistry was
employed to detect hepatic expressions of Bcl-2 and Bax, and Western blotting was used to detect Bax protein expression
changes. Results High-fat feeding resulted in significantly increased hepatocyte AI at 4-12 weeks and gradually increased
MPTP opening. In the high-fat diet group, hepatic Bcl-2 expression was detected but the positive cell number remained stable,
whereas Bax-positive cell number increased steadily with time with progressively increased intensity of Bax protein
expression, resulting in gradually decreased Bcl-2/Bax ratio. Conclusion Hepatocyte apoptosis occurs in the rat model of
NAFLD in close correlation with mitochondrial damage. Increased MPTP opening as the result of increased Bax expression
and aberrant Bcl-2/Bax ratio is an important mechanism of hepatocye mitochondrial damage in NAFLD.

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更新日期/Last Update: 1900-01-01