帕瑞昔布对缺血再灌注后肺组织血红素加氧酶-1表达水平及凋亡程度的影响*

Effect of Parecoxib on heme oxygenase-1 and apoptosis after lung ischemia/reperfusion in rats*

摘要:

目的 探讨不同剂量帕瑞昔布对大鼠肺缺血再灌注（IR）后肺组织内血红素加氧酶-1（HO-1）表达水平及凋亡程度的影响。方法 随机将40只雄性SD大鼠（280～300?g）分为5组：对照组（C组）、缺血再灌注组（IR组）、帕瑞昔布低剂量组（L组，2?mg/kg）、帕瑞昔布中剂量组（M组，10?mg/kg）及帕瑞昔布高剂量组（H组，20?mg/kg）。复制单侧肺IR模型，检测肺内丙二醛（MDA）和髓过氧化物酶（MPO）含量、肺组织湿重/干重，观察肺组织病理改变及凋亡情况，检测肺内HO-1表达。结果 与C组比较，其他4组肺内MDA和MPO含量、肺组织湿重/干重、肺内凋亡细胞均增加（P?<0.05），IR组增加最多，L组次之，M组和H组增加最少，且M组和H组差异无统计学意义（P?>0.05）。肺IR后，IR组肺损伤最严重，不同剂量帕瑞昔布处理后，肺损伤均减轻，M组和H组较L组减轻更明显。C组内HO-1表达低，其余4组均升高（P?< 0.05），其中L组较IR组升高，M组和H组较L组进一步升高，M组和H组差异无统计学意义（P?>0.05）。结论 帕瑞昔布可减轻肺IR损伤，在一定程度呈剂量依赖性，其机制可能与增加肺组织中HO-1表达有关。

Abstract:

Objective To explore the effect of different doses of Parecoxib on expression of HO-1 and apoptosis in rat model of lung ischemia-reperfusion (IR). Methods Totally 40 male adult Sprague-Dawley rats were randomly divided into 5 groups: control group (group C), ischemia reperfusion group (group I/R), Parecoxib group (2?mg/kg, group L), parecoxib group (10?mg/kg, group M), and parecoxib group (20?mg/kg, group H). Pulmonary ischemia-reperfusion injury model was established by blocking the left hilum of lungs. The wet/dry weight ratio (W/D), MDA and MPO of lung tissues were measured. Apoptosis, histological morphology of lung tissue as well as the expression of HO-1 in lung were detected. Results MDA, MPO, W/D and apoptosis rate were increased significantly in group I/R when compared with those in normal group, which was attenuated by treatment of Parecoxib (P??0.05). Pulmonary injury was the most severe in group I/R, which was attenuated by different doses of Parecoxib in dose dependent manner. HO-1 was only slightly expressed in group C, while significant upregulation of HO -1 was detected in group I/R (P??0.05) Conclusions Parecoxib attenuates lung ischemia-reperfusion injury dose-dependently probably through increased expression of HO-1.