摘要目的 研究姜黄素对博莱霉素诱导的大鼠肺纤维化形成上皮细胞凋亡及Bcl-2家族部分蛋白的影响,探讨姜黄素治疗肺纤维化的可能机制.方法 选取SD大鼠72只,随机分为4组,每组18只:空白组、模型组、姜黄素组、泼尼松龙组.应用博莱霉素(5 mg/kg)气管内注入建立实验性大鼠肺纤维化模型,空白组注入等量生理盐水,造模后第2天起,姜黄素组和泼尼松龙组分别给予姜黄素(300mg/kg)和泼尼松(5mg/kg)每日灌胃1次,其余两组每日给予1％羧甲基纤维素钠(10ml/kg)灌胃1次.各组动物于7d、14d、28 d随机处死6只,取肺组织行HE、Masson染色评价肺组织病理变化,消化法测定肺组织羟脯氨酸(HYP),TUNEL法检测肺组织细胞凋亡.SABC法检测Bid及Bcl-xl蛋白的表达.结果 姜黄素组肺纤维化程度、病理改变及HYP含量及上皮细胞凋亡指数较同时期模型组降低(P值均＜0.01)；姜黄素组肺组织肺泡上皮细胞Bid表达较同时期模型组比较差异无统计学意义.姜黄素组肺组织肺泡上皮细胞Bcl-xl表达较同时期模型组升高(P值均＜0.01).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能有效减轻肺纤维化程度,可能机制为姜黄素上调Bcl-xl的表达而非下调Bid表达来抑制上皮细胞凋亡.

abstractsObjective To investigate the expression of Bcl-2 family protein and apoptosis in epithelial cells of pulmonary fibrosis rats induced by bleomycin on different times,and observe the curcumin intervention in the formation stage of pulmonary fibrosis and explore its possible mechanism.Methods Seventy-two Sprague Dawley rats were randomly divided into four groups:control group,model group,cucumin group,and prednisone group.Model group,cucumin group,and prednisone group were induced to produce pulmonary fibrosis with bleomycin endotracheally while control group was given with normal saline instead in the same condition.From the second day after bleomycin administration,the curcumin group was given with curcumin (300 mg/kg) while prednisone group with prednisone (5 mg/kg) per day by intragastric administration,respectively.The control group and model group were given with 1％ sodium carboxymethyl cellulose (10 ml/kg).Six rats of each group were randomly sacrificed on 7th,14th,and 28th day after bleomycin administration,respectively.The histological changes of the lung were evaluated by HE and Masson staining.The level of hydroxyproline in lung tissue was assessed by digestion method.The immunohistochemical method was used to investigate the changes of Bid and Bcl-xl protein.TUNEL was used to detect the change of cell apoptosis.Results The cell apoptosis index,hydroxyproline and histological changes of the lung in cucumin group were lower than those in model group (P ＜0.01).There was no significant difference in the expression of Bid protein between model group and cucumin group.The expression of Bcl-xl protein in model group was lower than that in cucumin group (P ＜0.01).Conclusions Cucumin can reduce the expression of pulmonary fibrosis through inhibition of apoptosis of epithelial cells.It may up-regulate the expression of Bcl-xl in alveolar epithelial cells and bronchial cells of pulmonary fibrosis rats but not down-regulate the expression of Bid.