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ZnPP20mg/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 li