摘要
目的观察17-β雌二醇预处理对肝切除肝缺血再灌注损伤肝脏组织细胞凋亡及Bcl-2、Bax表达的影响，并探讨其肝保护的机制。方法建立大鼠肝切除肝缺血再灌注损伤模型，75只雄性SD大鼠随机分为3组：假手术组（Sham组）、缺血再灌注组（IR组）和17-β雌二醇预处理组（E2＋IR组）。检测各组大鼠再灌注后1h、3h、6h、12h、24h肝功能变化。光镜下观察肝组织病理学改变。TUNEI，法观察再灌注后12h大鼠肝细胞凋亡情况、流式细胞学方法测定再灌注后12h肝细胞凋亡率。Westernblot法检测再灌注后12hBcl-2和Bax的表达情况。结果与Sham组相比，在IR组各时间点均可见ALT和AST增高，且在再灌注后的12h达到了最高值；病理学检查可见肝细胞肿胀，肝窦变窄，嗜中性粒细胞浸润和片状坏死等变化；在再灌注后12h，凋亡细胞增多及细胞凋亡率明显升高；肝脏组织gcl-2表达减少，gax的表达增加。17-β雌二醇预处理组在灌注后各时间点ALT和AST值明显下降，肝脏病理损伤改善；在再灌注后12h，凋亡细胞减少及细胞凋亡率明显降低，肝脏组织Bcl-2表达增加，Bax的表达减少。结论17-β雌二醇对大鼠肝缺血再灌注损伤有明显的保护作用，其可能通过促进Bcl-2表达及抑制Bax表达，从而抑制肝细胞凋亡。
Objective To investigate the effects of 17-β estradiol on hepatocyte apoptosis and the expression of Bcl-2 and Bax in hepatic tissue after reduced-size ischemia-reperfusion injury and its mechanism in liver protection. Methods A rat model of reduced-size hepatic isehemia-reperfusion injury was established in 75 male Sprague-Dawley rats. They were randomly allocated into three groups： Sham group, ischemia-reperfusion （IR） group, and 17-β cstradiol （E2＋ IR） group. Liver functions, liver histology and hepatocellular apoptosis rates were observed after reperfusion. Hepatocellular ap optosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） method and the expression of Igcl-2 and Bax were determined by Western blotting. Results The levels of ALT and AST were higher and peaked after 12 h of reperfusion in the IR group com- pared with the sham group. The histological changes in the liver of the IR group consisted of hepato- cyte swelling, hepatic sinusoids narrowing, inflammatory cell infiltration and hepatocyte necrosis in some areas of the livers. The IR group also exhibited an increased rate of hepatocellular apoptosis at 12 h after reperfusion. The protein expression of Bel-2 decreased while the expression of Bax increased. In the 17- β estradiol group, the levels of ALT and AST were lower, the pathological changes were milder and the rate of hepatocellular apoptosis was lower at 12 h in comparison to those of the IR group. The expression of Bel-2 was higher and the expression of Bax was lower in the 17-β estradiol group in comparison to those of the IR group. Conclusions 17-β estradiol can relieve the hepatic ische- miareperfusion injury in rat livers. 17-β estradiol may inhibit apoptosis in hepatic tissue by up-regulating Bel-2 and down-regulating Bax, thus producing a protective effect on hepatic ischemi-reperfusion
出处
《中华肝胆外科杂志》
CAS
CSCD
北大核心
2012年第3期215-219,共5页
Chinese Journal of Hepatobiliary Surgery
关键词
雌激素
缺血再灌注损伤
肝脏
凋亡
Estrogen
Ischemia-reperfusion injury
Liver
Apoptosis
