国际麻醉学与复苏杂志   2011, Issue (3): 0-0
    
大鼠全肝缺血再灌注后肺细胞凋亡与Bcl-XL/Bax的表达及意义
姜春玲, 杨拔贤, 赵东, 咸云淑, 张卫星1()
1.北京大学深圳医院
Cellular apoptosis and Bcl-XL/Bax expression in lung during total hepatic ischemia-reperfusion in rats
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摘要:

目的 探讨大鼠全肝缺血再灌注后肺组织细胞凋亡与Bcl-XL/Bax的表达变化关系及其在肺损伤中的意义。方法 阻断肝门30min后开放血流,建立大鼠全肝缺血再灌注模型,48只SD大鼠分别于缺血前、再灌注0、0.5、1、3和6h处死取肺,原位末端转移酶(TUNEL)法检测细胞凋亡、PCR法检测Bcl-XL与Bax mRNA表达,同时检测肺湿/干重(W/D)比值及肺组织病理。结果 缺血再灌注后各时点肺组织W/D比值(0-6h依次为4.96±0.25,5.30±0.32,5.36±0.32,5.71±0.33,5.32±0.28)及细胞凋亡指数(0-6h依次为4.86±0.64%,7.64±0.61 %,15.60±0.59 %, 19.74±0.71 %,27.48±0.88 %),与缺血前相比(分别为4.59±0.24与4.00±0.45%)均显著增高(p均<0.05),并分别于再灌注3h与6h达峰值;Bcl-XL/Bax比值于缺血再灌注后各时点(0-6h依次为1.01±0.13,0.43±0.03,0.51±0.07,0.62±0.06,0.62±0.07)均较缺血前(1.48±0.11)显著降低(p均<0.01);病理学方面,缺血再灌注后肺泡腔完整性破坏,间隔增厚,并可见中性粒细胞浸润,这些改变于再灌注1h已较明显,再灌注3h最重。双变量相关分析显示,肺组织细胞凋亡指数与W/D比值呈正相关,相关系数r = 0.56(p<0.01),与Bcl-XL/Bax比值呈负相关,相关系数r = -0.55(p<0.01)。结论 大鼠全肝缺血再灌注可引起肺组织细胞凋亡加剧,并由此促进肺损伤,此过程中Bcl-XL/Bax比值降低可能参与介导了细胞凋亡。

关键词: 细胞凋亡;Bcl-XL;Bax;再灌注损伤
Abstract:

Objective: To explore the changes of cellular apoptosis and expression of Bcl-XL/Bax in lung during total hepatic ischemia-reperfusion (I/R ) in rats ,and the relationship between their changes and lung injury. Methods: Total hepatic I/R was produced by occlusion of hepatic helium for 30 minutes, and the occlusion was then released for reperfusion. 48 healthy male SD rats weighing 250~300g were were killed respectively prior to ischemia and at 0h, 0.5h, 1h, 3h ,6h of reperfusion,and the lung tissue was taken for determation of apoptotic cells , Bcl-XL mRNA,Bax mRNA expression ,wet/dry(W /D) ratio and histological examination. Results: After hepatic I/R the W /D ratio(4.96±0.25,5.30±0.32,5.36±0.32,5.71±0.33 and 5.32±0.28)and apoptotic index (4.86±0.64%,7.64±0.61 %,15.60±0.59 %, 19.74±0.71 % and 27.48±0.88 %)were increased(P<0.05),compared with preischemia(4.59±0.24 and 4.00±0.45%).And the Bcl-XL/Bax ratio after hepatic I/R (1.01±0.13,0.43±0.03,0.51±0.07,0.62±0.06,0.62±0.07) were decreased(P<0.01), compared with preischemia(1.48±0.11). Histological examination revealed that the alveolar architecture was destroyed,with interstitial thickening and neutrophil infiltration after hepatic I/R. Correlate analysis revealed that the apoptotic index showed a positive correlation with the W/D ratio(r= 0.56,P<0.01) and a negative correlation with the Bcl-XL/Bax ratio(r= -0.55,P<0.01). Conclusion: Total hepatic ischemia-reperfusion in rats could lead to aggravation of pneumocyte apoptosis ,which promoted acute lung injury,and the reduction of Bcl-XL/Bax ratio during this period may mediate the occurrence of apoptosis .

Key words: Apoptosis; Bcl-XL;Bax;Reperfusion injury