姜黄素对内毒素诱导的急性肺损伤的保护作用及机制研究

Protective effects of curcumin on acute lung injury induced by LPS in rats

目的探究姜黄素在内毒素(LPS)诱导大鼠急性肺损伤(acute lung injury,ALI)中的保护作用,并明确其作用机制。方法 80只健康雄性12周龄SD大鼠,体质量(200±25)g,由第三军医大学实验动物中心提供。随机分为:①正常对照组:3 mL/kg生理盐水腹腔注射;②溶媒组:1 mL/kg DMSO和2 mL/kg生理盐水腹腔注射;③模型组:5 mg/kg LPS腹腔注射;④姜黄素组:先注射5 mg/kg LPS,30 min后注射200 mg/kg姜黄素腹腔注射。每组20只。分别于0、6、12、24 h选取5只大鼠行血气分析,Western blot检测肺组织MMP2、MMP9、ELISA检测IL-6和TNF-α的表达水平以及MPO活性。结果正常对照、溶媒组大鼠组内和组间PaO2、PaO2/FiO2、MMP2、MMP9、IL-6和TNF-α的表达水平以及MPO活性比较均无显著性差异(P>0.05)。与0 h比较,模型组、姜黄素组在6、12、24等3个时点PaO2、PaO2/FiO2显著降低(P<0.05),MMP2、MMP9、IL-6和TNF-α的表达水平以及MPO活性显著升高(P<0.05)。与正常对照组相比,模型组、姜黄素组PaO2、PaO2/FiO2均显著降低(P<0.05),MMP2、MMP9、IL-6和TNF-α的表达水平以及MPO活性显著升高(P<0.05)。与模型组相比,姜黄素组PaO2、PaO2/FiO2在6、12、24 h均显著升高(P<0.05),MMP2、MMP9、IL-6和TNF-α的表达水平以及MPO活性显著降低(P<0.05)。结论姜黄素能有效减轻由LPS诱导的ALI,其机制可能与下调MMP2和MMP9蛋白的表达、进而减少肺组织中性粒细胞的聚集和活化、最终显著减轻肺组织炎症反应有关。

Objective To observe the protective effect of curcumin on acute lung injury induced by LPS in rats and further to explore the molecular mechanism.Methods Eighty 12-week-old SD rats weighing 200 ± 25 g,aged 12 weeks,purchased from the Experimental Animal Center of the Third Military Medical University were randomized into 4 groups and treated as follows：control group were intraperitoneal injected with saline（3 mL /kg）,the solvent group was injected with DMSO（1 mL /kg） in half an hour after intraperitoneal injection of saline（2 mL /kg）,model group was injected with 5 mg /kg LPS,and curcumin treatment group was injected with curcumin 200 mg /kg in half an hour after intraperitoneal injection of LPS.Arterial blood samples were collected in 0,6,12,and 24 h after drug administration for blood gas analysis,then the lung pathology was assessed,meanwhile the expression levels of MMP2 and MMP9 were measured by Western blotting and the expression levels of IL-6 and TNF-α and the activity of MPO were determined by ELISA.Results There was no significant difference between and within control group and solvent group.Compared with 0 h,PaO2 and PaO2/FiO2 were significantly decreased,the expression levels of MMP2,MMP9,IL-6 and TNF-α and the activity of MPO were significantly decreased in model group and curcumin treatment group at 6,12 and 24 h（P 0.05）.Compared with control group and solvent group,PaO2 and PaO2/FiO2 were significantly decreased,the expression levels of MMP2,MMP9,IL-6 and TNF-α and the activity of MPO were significantly decreased in model group and curcumin treatment group（P 0.05）.compared with model group,PaO2 and PaO2/FiO2 were significantly increased,the expression levels of MMP2,MMP9,IL-6 and TNF-α and the activity of MPO were significantly decreased in curcumin treatment group（P 0.05）.Conclusion Curcumin have a protective effect on acute lung injury induced by LPS in rats,and the protective mechanisms may be related to decreased MMP2 and MMP9 protein expression.