N-乙酰半胱氨酸对博来霉素诱导的大鼠肺纤维化的干预作用

目的探讨N-乙酰半胱氨酸（N acetylcysteine,NAC）对博来霉素诱导的大鼠肺纤维化的干预作用及可能的机制.方法 100只SD雄性大鼠随机分为健康对照组、肺纤维化模型组、地塞米松干预组和NAC干预组,每组25只.各组分别于第1,3,7,14,28 d各处死5只,收集肺组织作切片行HE和Masson染色判断肺组织肺泡炎和肺纤维化程度,行免疫组化测定肺组织转化生长因子β1（TGF-β1）,收集血清和支气管肺泡灌洗液行Elisa检测TGF-β1,收集肺组织检测羟脯氨酸含量.结果与模型组比较,两个干预组的肺泡炎及肺纤维化程度均明显减轻（P〈0.05）,肺组织TGF-β1的蛋白表达水平明显降低（P〈0.05）,血清和支气管肺泡灌洗液的TGF-β1的蛋白表达水平明显降低（P〈0.05）,其中NAC干预组较地塞米松干预组更为显著（P〈0.05）,与模型组比较,两个干预组的羟脯氨酸含量也明显降低（P〈0.05）,其中NAC干预组较地塞米松干预组更为显著（P〈0.05）.结论 NAC具有与地塞米松相似的较强的抗纤维化效应,机制可能为通过抑制细胞因子TGF-β1的表达来抑制肺纤维化.

The Role of N-acetylcysteine in Suppressing Bleomycin-induced Pulmonary Fibrosis in rats

Objective To investigate the role and mechanism of N-acetylcysteine in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods One hundred SD rats were randomly divided into four groups（25 rats in each group）：normal group,bleomycin-induced pulmonary fibrosis model group,dexamethasone-treated group,and N-acetylcysteine-treated group.Five rats in each group were randomly killed on the 1st day,3rd day,7th day,14th day and 28 th day,respectively,and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis,respectively.Histoimmunochemical staining was used to determine the protein levels of transforming growth factor-β1（TGF-β1）.Serum and bronchoalveolar lavage fluid（BALF） were harvested to determine the protein levels of transforming growth factor-β1（TGF-β1）by ELISA,lung tissue samples were harvested to determine the concentration of hydroxyproline（HYP）.Results Histopathological study showed that treatment with either dexamethasone or N-acetylcysteine remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis（compared with model group,P 0.05）.Histoimmunochemical study suggested that both dexamethasone and N-acetylcysteine inhibited the expression of TGF-β1（compared with model group,P 0.05）,there was the same tendency of changes in serum and bronchoalveolar lavage fluid（BALF）as that in the tissue,and the suppression of TGF-β1 was more obvious in N-acetylcysteine-treated group than those in dexamethasone-treated group（P 0.05）.The treatment with either dexamethasone or N-acetylcysteine remarkably reduced contents of hydroxyproline（HYP）in lung tissue（compared with model group,P 0.05）,and the suppression of contents of hydroxyproline（HYP）was more obvious in N-acetylcysteine-treated group than that in dexamethasone-treated group（P 0.05）.Conclusions N-acetylcysteine has potent anti-fibrosis effect similar to dexamethasone.Such effect may result from inhibition of the cytokine TGF-β1