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

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。

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

AIM:To investigate the effects of curcumin pretreatment on heme 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+I/R group(Cur-I/R group),Zinc protoporphyrin IX+Curcumin+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 pulmonary 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 with Sham group(P<0.01).Lung injury 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<0.01).CONCLUSION: Curcumin pretreatment has protective effects against lung injury induced by I/R of hind limbs in rats through up-regulation of HO-1 expression in the lung tissues.