姜黄素预处理对大鼠肢体缺血再灌注肺损伤时血红素加氧酶-1的影响

Effects of curcumin pretreatment on heme oxygenase-1 in lung injury induced by ischemia-reperfusion of hind limbs in rats

目的:探讨姜黄素预处理对大鼠肢体缺血再灌注肺损伤时血红素加氧酶-1(HO-1)的影响。方法:建立大鼠肢体缺血2h再灌注3h肺损伤模型。60只大鼠随机等分为5组:假手术组(Sham)、姜黄素组(Cur)、缺血再灌注组(I/R)、姜黄素+缺血再灌注组(Cur-I/R)和锌原卟啉IX(ZnPP)+姜黄素+缺血再灌注组(ZnPP-Cur-I/R)。ZnPP-Cur-I/R组于缺血前24h经腹腔注射ZnPP 20mg/kg,Cur组、Cur-I/R组和ZnPP-Cur-I/R组分别于缺血前2h经腹腔注射姜黄素200mg/kg,其余各组给予等容量生理盐水。除Sham组和Cur组外,其余各组行肢体缺血再灌注。观察肺组织病理学变化,测定肺组织损伤评分、湿/干重比(W/D)、中性粒细胞(PMN)数目和HO-1mRNA及其蛋白表达的情况。结果:与Sham组比较,I/R组肺组织损伤较重,肺损伤评分、W/D及PMN计数升高,HO-1mRNA及其蛋白表达上调(P<0.01);与I/R组比较,Cur-I/R组肺组织损伤减轻,肺损伤评分、W/D及PMN计数降低,HO-1mRNA及其蛋白表达上调(P<0.01);与Cur-I/R组比较,ZnPP-Cur-I/R组肺组织损伤加重,肺损伤评分、W/D及PMN计数升高,HO-1mRNA及其蛋白表达下调(P<0.01)。结论:姜黄素预处理可通过上调肺组织HO-1的表达减轻大鼠肢体缺血再灌注肺损伤。

AIM. To investigate the effects of curcumin pretreatment on heine oxygenase-1 （HO-1） in lung injury induced by ischemia- reperfusion （I/R） of hind limbs in rats. METHODS. The model of lung injury was established by occlusion of bilateral femoral arteries for 2 h followed by 3 h reperfusion in rat. Sixty SD rats were randomly divided into five equal groups. Sham group, Curcumin group （Cur group）, I/R group, Curcumin-l-I/R group （Cur-I/R group）, Zinc protoporphyrin IX-l- Curcumin if- I/R group （ZnPP-Cur-I/R group）. ZnPP-Cur-I/R group received ZnPP 20 mg/kg via intraperitoneal injection 24 h before ischemia. Cur, Cur-I/R and ZnPP-Cur-I/R groups received curcumin 200 mg/kg respectively via intraperitoneal injection 2 h before ischemia. I/R of hind limbs was induced in three I/R groups. The lungs were removed for pathologic examination and determination of the lung Wet/dry weight ratio （W/D）, lung injury score and polymorphonuclear neutrophil （PMN） count. The expression of HO-1 mRNA and protein in lung tissues was detected using RT-PCR and Western blot analysis respectively. RESULTS. Alveolar edema, localized pul-monary atelectasis and large amount of PMN infiltration were found in I/R group and were ameliorated in Cur-I/R group. Lung injury score, W/D ratio and PMN count were increased in I/R group as compared 0.01）. Lung injury with Sham group （P 〈2 score, W/D ratio and PMN count were significantly decreased in Cur-I/R group as compared with I/R group （P（0.01）. HO-1 mRNA and protein expression was significantly up-regulated in Cur-I/R group than in Sham and I/R groups （P 〈 0.01）. Compared with Cur-I/R group, the beneficial effects of curcumin were abolished, lung injury score, W/ D ratio and PMN count were significantly increased, and expression of HO-1 mRNA and protein was down-regulated in ZnPP-Cur-I/R group （P 〈20. 01）. CONCLUSION： Curcumin pretreatment has protective effects against lung injury induced by I/R through up-regulation of lung tissues. of hind limbs in rats HO-1 expression in the lung tissues.