曲尼司特抗大鼠肺纤维化的作用及机制

目的：探讨曲尼司特对肺纤维化的治疗作用及机制。方法：48只Sprague—Dauley大鼠随机分为正常对照组（N组）、肺纤维化模型组（M组）和曲尼司特治疗组（Q组）各16只，分别在14、28d处死8只，每组大鼠分别采用HE染色、Masson染色行肺泡炎、肺纤维化程度分级。采用免疫组化法检测肺组织NF—κB；荧光定量PCR技术测定TGF-β1 mRNA表达；样本碱水解法测定羟脯氨酸（HYP）；DTNB法测定超氧化物歧化酶（SOD）；硫代巴比妥酸法测定丙二醛（MDA）。结果：M组的肺泡炎及肺纤维化程度及HYP含量、NF—κB、转化生长因子-β1（TGF—β1）mRNA及MDA含量均较N组显著升高（P〈0．01）。Q组大鼠肺泡炎及肺纤维化程度及HYP含量、NF-κB、TGF-β1 mRNA MDA含量均较M组显著降低（P〈0．01）。结论：曲尼司特可能是通过抑制氧自由基生成而下调了NF-κB的活性，从而抑制了TGF-β mRNA的表达而发挥抗肺纤维化作用。

Inhibitory effects and mechanisms of tranilast on pulmonary fibrosis in rats

To explore the inhibitory effects and mechanisms of tranilast on bleomycin-induced pul-monary fibrosis in rats. METHODS: Fourty-eight Sprague-Dauley rats were randomly divided into normal control group (Group N, n = 16) , pulmonary fibrosis model group (Group M, n = 16) , and tranilast treat-ment group (Group Q, n = 16). Eight rats in each group were sacrificed on days 14 and 28 following the day of animal model establishment. The degree of air-sacculitis and pulmonary fibrosis were detected by HE and Masson staining in each group rats. The concentra-tions of NF-κB , expressions of TGF-β_1 mRNA and con-centrations of Hydroxyproline (HYP), SOD and MDA in lung tissue were detected by the immunohistoche-mical method,fluorescent quantitative PCR, allaki hydrolysis, DTNB and thiobarbituric acid method in each group, respectively. RESULTS: The concentra-tions of NF-κB , expressions of TGF-β_1, mRNA and con-centrations of HYP, SOD and MDA in lung tissue were significantly higher in Group M than in Group N ( P < 0.01) and was significantly lower in Q group than in M group (P<0.01). CONCLUSION: The anti-pulmo-nary fibrosis effect of tranilast may be achieved through inhibited the generation of oxygen free radicals and thus decreased the activity of NF-κB, thereby inhibited TGF-β mRNA expression.