姜黄素对肺纤维化大鼠I型胶原蛋白和转化生长因子β1mRNA表达的影响

摘要

Objective To study the eitects ot curcumin on the expressions of collagen type I protein and transtorming growth factor-β1 mRNA in lung tissues of rats with pulmonary fibrosis.Methods 96 male SD rats were randomly divided into four groups with 24 rats in each group:the normal control group,the model group,the prednisone treated group,and the curcumin treated group.Pulmonary fibrosis was induced by intrabronchial injection of bleomycin A5.From the 15th day after bleomycin administration,rats in the prednisone treated group and the curcumin treated group were given prednisone(5 mg/kg)or curcumin(300 mg/kg) respectively once daily by intragastric administration.In the same way,rats in the normal control group and the model group were given 1% Sodium Carboxymethyl Cellulose(10 ml/kg)once daily.The histological changes of lung tissue were evaluated by Haematoxylin-eosin(HE)and Masson's trichrome.The rats were randomly sacrificed on the 21st,28th,42nd and 56th day after bleomycin administration.The type I collagen expression was analyzed by immunohistochemistry.The transforming growth factor-β1(TG-β1)mRNA expression of lung was detected by the semi-quantitative reverse transcription polymerase chain reaction(RT-PCR).Results Pulmonary fibrosis in the eurcumin treated group was significantly reduced as cornpared with the model group and the prednisone treated group on the 42nd and 56th day(P＜0.05).The expression of type I collagen protein in the ourcumin treated group was significantly decreased than that in the model group and the prednisone treated group on the 28th,42nd and 56th day after bleomycin administration(P＜0.05).The TGF-β1 mRNA expression in the curcunfin treated group was O.61±0.09 and 0.48±0.16 respectively on the 21st and 28th day after bleomycin administration(P＜0.05).It was significantly decreased than that in the model group on the 21st,28th day after blenmycin administration and lower as compared with the prednisone treated group on the 21st day(P＜0.05).Conclusion Curcumin could suppress BLM-induced pulmonary fibrosis in rats at the fibrosing stage,with the possible mechanism of inhibiting the synthesis and deposition of type I collagen protein and depressing the overepression of TGF-β1 mRNA.The therapeutic effect ot curcumin on pulmonary fibrosis is better than prednisone.%目的 探讨姜黄素对肺纤维化大鼠I型胶原蛋白和转化生长因子β1(TGF-β1)mRNA表达的影响.方法 健康雄性SD大鼠96只,随机分为正常对照组、模型组、泼尼松治疗组(泼尼松组)、姜黄素治疗组(姜黄素组),每组24只.除正常对照组外,其余各组大鼠气管内一次性注入博莱霉素诱导肺纤维化.造模后第15天起,姜黄素组和泼尼松组分别给予姜黄素(300 mg/kg)和泼尼松(5 mg/kg),每日灌胃1次,其余2组每日给予质量分数为1%的羧甲基纤维素钠(10 ml/kg)灌胃1次,直至处死动物.各组动物分别于造模后第21、28、42、56天随机处死6只.HE、Masson染色观察肺组织病理变化,免疫组化(EnVision二步法)测定肺组织中I型胶原蛋白表达,反转录聚合酶链反应(RT-PCR)法测定肺组织mRNA的表达.结果 第42、56天姜黄素组肺纤维化程度明显低于模型组和泼尼松组,差异有统计学意义(P＜0.05);第28、42、56天姜黄素组肺组织I型胶原蛋白表达水平明显低于模型组和泼尼松组,差异有统计学意义(P＜0.05);姜黄素组21、28 d肺组织TGF-β1mRNA表达水平分别为0.61±0.09、0.48±0.16,明显低于同期模型组,差异有统计学意义(均P＜0.05);21 d姜黄素组肺组织TGF-β1mRNA表达水平明显低于泼尼松组,差异有统计学意义(P＜0.05).结论 在博莱霉素诱导的大鼠肺纤维化形成阶段应用姜黄素干预,抑制肺纤维化的发展,疗效优于传统治疗药物泼尼松.姜黄素可抑制I型胶原蛋白的合成与沉积,降低肺组织TGF-β1mRNA的表达.