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  

Cellular apoptosis and BcI-XL/Bax expression in lung during total hepatic ischemia-reperfusion in rats

作　　者：姜春玲[1] 杨拔贤[2] 赵东[2] 咸云淑[1] 张卫星[1] 

机构地区：[1]深圳市北京大学深圳医院ICU,518036 [2]北京大学人民医院麻醉科

出　　处：《国际麻醉学与复苏杂志》2011年第3期291-293,302,共4页International Journal of Anesthesiology and Resuscitation

摘　　要：目的 探讨大鼠全肝缺血，再灌注（ischemidreperfusion，I／R）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 48只sD大鼠随机分成6组（n=8）：①缺血前组；②再灌注Oh组；③再灌注0．5h组；④再灌注1h组；⑤再灌注3h组；⑥再灌注6h组。阻断肝门30min后开放血流，建立大鼠全肝I／R模型，48只SD大鼠分别于缺血前、再灌注0、0．5、1、3、6h处死取肺，原位末端转移酶（terminaldeoxynueleotidyltransferasedUTPnickendlabeljng，TUNEL）法检测细胞凋亡、PCR法检测Bcl-XL与BaxmRNA表达，同时检测肺湿／干重（W／D）比值及肺组织病理。结果 I／R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％）差异有统计学意义（P〈0．05），并分别于再灌注3h与6h达峰值；Bcl-XL／Bax比值于I／R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）差异有统计学意义（P〈0．01）；病理学方面，I／R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I／R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-XUBax比值降低可能参与介导了细胞凋亡。Objective To explore the relationship of cellular apoptosis and expression of Bcl-XL/Bax in lung during total hepatic ischemia/reperfusion （I/R） in rats , and its importance in lung injury. Methods 48 healthy male SD rats were randomly divided into 6 groups（n=8 ）： ① pre-ischemia group, ② reperfusion 0 h group, ③ reperfusion 0.5 h group,④ reperfusion lh group, ⑤ reperfusion 3 h group,⑥ reperfusion 6 h group.Total hepatic I/R was developed by occlusion of hepatic helium for 30 minutes, and the occlusion was then released for reperfusion. 48 healthy male Sprague Dawley rats weighing 250 g-300 g were killed respectively prior to ischemia and at 0, 0.5, 1, 3,6 h after reperfusion, and the lung tissue was taken for determination 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, 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 respectively （P〈0.05）, compared with preischemia （4.59±0.24）% and （4.00±0.45）%. 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. Correlation analysis indicated 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. Reduction of BcI-XL/Bax ratio during this period might mediate the occurrence of apoptosis .

关 键 词：细胞凋亡 BCL-XL BAX 再灌注损伤 

分 类 号：R363[医药卫生—病理学]