百草枯中毒大鼠肺TGF-β_1和c-Jun的表达及姜黄素的干预作用  

The Effect of Curcumin on the Expression of TGF-β_1 and c-Jun in the Rat Lung Injured by Paraquat

作　　者：吴伟[1] 刘莹[2] 胡明[3] 于淼淼[4] 

机构地区：[1]中国医科大学附属第一医院急诊科,沈阳110001 [2]天津医科大学总医院急诊科,天津300000 [3]北京306医院急诊科,北京100101 [4]辽宁省肿瘤医院重症监护病房,沈阳110001

出　　处：《中国医科大学学报》2011年第1期12-16,共5页Journal of China Medical University

基　　金：辽宁省教育厅高校科研计划项目(L2010684)

摘　　要：目的通过检测百草枯中毒大鼠肺组织中转化生长因子β(1TGF-β1)及原癌c-jun基因表达水平的变化趋势和观察姜黄素减轻百草枯中毒大鼠肺间质纤维化,探讨姜黄素的干预作用机制。方法 8周龄清洁级Wistar雄性大鼠随机分为百草枯中毒组(百草枯50mg/kg一次性灌胃染毒)和姜黄素干预组(百草枯灌胃染毒后姜黄素200mg·kg-·1d-1一次腹腔内注射)。观察动物中毒反应,到达观察终点的动物麻醉处死,HE和Masson染色观察肺组织大体病理变化,测定肺湿重并计算肺系数。用羟脯氨酸含量确定肺纤维化程度。免疫组化法检测TGF-β1和c-Jun表达。结果姜黄素干预组动物生存率为67%,百草枯中毒组生存率为35%,两组比较有统计学差异(P<0.05)。百草枯中毒组出现肺水肿、出血、肺泡炎表现,中毒3d时炎性表现最明显,14d后纤维细胞增生、肺泡壁增厚。姜黄素减少了肺泡炎并降低了纤维化程度。姜黄素干预组与百草枯中毒组相比,14d后肺组织羟脯氨酸含量明显降低(P<0.05)。百草枯中毒组7d后TGF-β1表达水平开始开高。姜黄素治疗14d后TGF-β1表达水平明显低于百草枯中毒组(P<0.01)。百草枯中毒组1d后c-Jun表达增加,但与姜黄素干预组比较无统计学差异。结论姜黄素通过抑制肺组织TGF-β1表达,减少百草枯中毒大鼠胶原沉积,减轻肺纤维化程度,并非通过抑制c-Jun表达而发挥其作用。Objective To investigate TGF-β1 and c-Jun expression in the lungs of paraquat-poisoned rats and to evaluate the effect of curcumin on paraquat-induced pulmonary fibrosis.Methods Wistar rats were randomly divided into paraquat-poisoned group（PQ group,with PQ 50 mg/kg i.g） and curcumin-treated group （PC group,with PQ 50 mg/kg i.g and with curcumin 200 mg/kg,i.p.once a day） .At the given time points,animals were scarified with lungs harvested.The body weight and lung wet weight of rats were measured and lung indice of rats in each group were compared.Pathological appearances of lung tissue were observed by HE staining and Masson staining.Hydroxyproline（HYP） in lung tissue were used to determine the severity of pulmonary fibrosis.The expression of TGF-β1 and c-Jun in lung tissue were examined by immunohistochemistry.Results The survival rates of mice were 67% and 35% in the PC and PQ groups with significant difference （P 〈 0.05）.Pulmonary edama,hemorrhage or extrusion of inflammatory cells was observed in PQ group,especially during the first 3 days.After 14 d,the production of collagen fibers and fibrous thickening of the alveolar wall were seen in PQ intoxication.Curcumin could relieve the lung inflammation and fibrosis in our study.The level of HYP of PC group were significantly lower than that of PQ exposure after 14 d （P 〈 0.05）.The expression TGF-β1 was increased in PQ exposure after 7 d.The intensity of the expression TGF-β1 in PC group was significantly lower than that in PQ group after 14 d （P 〈 0.05）.After 1 d,the expression c-Jun in PQ group were not significantly higher than that in PC group （P 〉 0.05）.Conclusion Curcumin can relieve paraquat-induced collagen deposition and pulmonary fibrosis due to its inhibitory effect of TGF-β1 expression,but not c-Jun expression.

关 键 词：肺纤维化 原癌c-jun基因 转化生长因子Β1 百草枯 姜黄素 

分 类 号：R587.11[医药卫生—内分泌]