姜黄素对肺纤维化小鼠的保护作用及其机制研究

Protective effect of curcumin on pulmonary fibrosis in mice and its mechanism

目的 研究姜黄素对百草枯所致小鼠肺纤维化的影响,并探讨其保护机制.方法 将60只雄性昆明小鼠随机分为对照组、模型组及姜黄素20、40、80 mg/kg干预组和地塞米松5 mg/kg组,每组10只.制备小鼠肺纤维化模型的同时ig给药,对照组和模型组ig0.1 mL的0.9%的生理盐水,每2天给药1次,第28天眼球取血后处死所有小鼠.取左侧肺组织制作组织切片进行HE染色和Masson染色,右侧肺组织进行羟脯氨酸(HYP)、丙二醛(MDA)以及超氧化物歧化酶(SOD)测定.采用酶联免疫吸附法(ELISA)测定血清中肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、基质金属蛋白酶9(MMP-9)水平.通过免疫组化分析肺组织中核因子NF-κB表达水平.结果 姜黄素20、40、80 mg/kg干预组及地塞米松组的肺纤维化程度明显轻于模型组.与模型组比较,姜黄素各剂量组和地塞米松组HYP及MDA水平均显著降低,而SOD含量显著升高(P<0.01);与地塞米松组比较,姜黄素40、80 mg/kg干预组MDA水平显著降低(P<0.05),姜黄素80 mg/kg干预组的SOD水平显著升高(P<0.05).与模型组相比,姜黄素20、40、80 mg/kg干预组和地塞米松组血清中的TNF-α、IL-6、MMP-9浓度降低明显(P<0.01),且姜黄素40、80 mg/kg干预组的TNF-α、MMP-9水平低于地塞米松组(P<0.05).与模型组比较,姜黄素20、40、80 mg/kg干预组和地塞米松组肺组织细胞核NF-κB表达水平显著降低(P<0.01).结论 姜黄素可有效降低肺纤维化模型小鼠HYP、MDA含量、血清中TNF-α、IL-6浓度,下调肺组织NF-κB蛋白表达水平,改善肺部形态学病变,增强抗氧化能力,对肺纤维化小鼠产生保护作用.

Objective To investigate the effects of curcumin on paraquat-induced pulmonary fibrosis in mice and explore its protective mechanism.Methods 60 male Kunming mice were randomly divided into control group,model group,curcumin 20,40,80 mg/kg intervention group and dexamethasone group,each group had 10 mice.The pulmonary fibrosis model of mice was prepared by intragastric administration.The control group and the model group were ig administered with 0.9%saline 0.1 mL,once every 2 days,and all mice were killed on the 28th day after eyeball blood was taken.The left pulmonary was carried out for HE staining and Masson staining,and the right pulmonary was used for the detection of HYP,MDA,and SOD.Serum levels of TNF-α,IL-6,and MMP-9 were determined by ELISA.Immunohistochemistry was performed to analyze the expression level of nuclear factor NF-κB in lung tissues.Results The degree of pulmonary fibrosis in the curcumin 20,40,80 mg/kg intervention group and dexamethasone group were significantly less than that in the model group.Compared with model group,HYP and MDA levels of curcumin in each dose group and dexamethasone group were significantly reduced,while SOD was significantly increased(P<0.01).Compared with dexamethasone group,MDA level in curcumin 40 and 80 mg/kg intervention group was significantly reduced(P<0.05),while SOD level in curcumin 80 mg/kg intervention group was significantly increased(P<0.05).Compared with model group,the serum concentrations of TNF-α,IL-6,and MMP-9 in the 20,40 and 80 mg/kg intervention group and dexamethasone group were significantly decreased(P<0.01),and the levels of TNF-αand MMP-9 in the 40 and 80 mg/kg intervention group were lower than those in the dexamethasone group(P<0.05).Compared with the model group,the expression level of nuclear NF-κB was significantly decreased in the intervention group with curcumin at 20,40 and 80 mg/kg and the dexamethasone group(P<0.01).Conclusion Curcumin can effectively reduce the content of HYP and MDA,as well as the concentrations of TNF-αand IL-6 in serum of pulmonary fibrosis model mice,down-regulate the expression level of NF-κB protein in lung tissues,improve lung morphological lesions,enhance antioxidant ability,and have a protective effect on pulmonary fibrosis mice.