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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 explore the protective effect of curcumin on acute lung injury (ALI) induced by endotoxin (LPS) in rats and its mechanism. Methods Eighty healthy, male, 12-week-old SD rats, weighing 200 ± 25 g, were provided by Experimental Animal Center of Third Military Medical University. Were randomly divided into: ① normal control group: 3 mL / kg saline intraperitoneal injection; ② vehicle group: 1 mL / kg DMSO and 2 mL / kg saline intraperitoneal injection; ③ model group: 5 mg / kg LPS intraperitoneal injection; ④ Curcumin group: The first injection of 5 mg / kg LPS, 30 min after injection of 200 mg / kg curcumin intraperitoneal injection. Each group of 20. Five blood samples were collected at 0, 6, 12 and 24 h respectively for blood gas analysis. MMP2 and MMP9 in lung tissue were detected by Western blot. The expression of IL-6 and TNF-α and the activity of MPO were detected by ELISA. Results There was no significant difference in the expression levels of PaO2, PaO2 / FiO2, MMP2, MMP9, IL-6 and TNF-α and the MPO activity between the two groups in the vehicle group and in the normal group (P> 0.05). Compared with 0 h, PaO2 and PaO2 / FiO2 were significantly decreased (P <0.05), MMP2, MMP9, IL-6 and TNF-α in model group and curcumin group at 6, 12, MPO activity was significantly increased (P <0.05). Compared with the normal control group, PaO2 and PaO2 / FiO2 in the model group and the curcumin group were significantly decreased (P <0.05), and the expression levels of MMP2, MMP9, IL-6 and TNF-α and MPO activity were significantly increased (P < 0.05). Compared with the model group, PaO2 and PaO2 / FiO2 in curcumin group were significantly increased at 6, 12 and 24 hours (P <0.05), and the expression of MMP2, MMP9, IL-6 and TNF-α and MPO activity were significantly decreased (P <0.05). CONCLUSION: Curcumin can effectively reduce the ALI induced by LPS, and its mechanism may be related to down-regulating the expression of MMP2 and MMP9 protein, thereby reducing the aggregation and activation of neutrophils in lung tissue and ultimately reducing the inflammatory reaction in lung tissue.