双环醇改善大鼠肺纤维化的机制研究

Study on the Mechanism of Bicyclol for Improving Pulmonary Fibrosis in Rats

关键词:  肺纤维化  双环醇  Bcl-2  Bax  cleaved caspase 3

Key words:  pulmonary fibrosis  bicyclol  Bcl-2  Bax  cleaved caspase 3

摘要:

目的 观察双环醇对博来霉素诱导大鼠肺纤维化的干预作用,并进一步探讨其可能的作用机制。方法 将♂SD大鼠随机分为5组:对照组,模型组,双环醇低、中、高剂量组,每组10只。除对照组外,其他4组均用单次气管内注入博来霉素的方法复制大鼠肺纤维化模型,造模成功24 h后双环醇各剂量组分别给予不同剂量双环醇片溶解后灌胃,对照组和模型组相同条件下注入等体积生理盐水,观测5组大鼠一般情况,根据双环醇不同剂量组大鼠生存率情况,选择生存率最高组和对照组、模型组进行下一步实验。观测3组大鼠肺组织病理变化,行肺纤维化Ashcroft评分及肺泡间隔厚度测定,检测肺组织中pro-caspase 3、cleaved caspase 3、Bcl-2和Bax的表达。结果 各造模组中双环醇高剂量组生存率最高(P<0.05),故选择双环醇高剂量组作为双环醇组继续实验。与模型组相比,双环醇组肺泡结构破坏及肺间质纤维化程度减轻,肺纤维化Ashcroft评分明显降低(P<0.01),肺泡间隔厚度明显变薄(P<0.01),Bax和cleaved caspase 3表达水平均显著降低(P<0.01),Bcl-2升高(P<0.01)。结论 双环醇对博来霉素诱导大鼠肺纤维化具有明显的保护作用,而其作用机制可能与通过干预Bcl-2、Bax和cleaved caspase 3影响细胞凋亡改善肺纤维化有关。

Abstract:

OBJECTIVE To investigate the interventional effectiveness and the relevant mechanisms of bicyclol on bleomycin-induced pulmonary fibrosis(BPF) in rats. METHODS The male SD rats were randomly divided into 5 groups:control group, model group, low, medium and high dose of bicyclol groups, 10 rats per group. In addition to the control group, the other four groups were established to the pulmonary fibrosis model by bleomycin intra-tracheal injection. After 24 h of successful model, the different dose groups of bicyclol were intragastrically administered with different doses of dissolved bicyclol tablets, the control group and the model group were injected with equal volume of saline under the same conditions. All groups were observed the general condition, according to the survival rate of rats in different dose groups of bicyclol, the group with the highest survival rate, the control group and the model group were selected for the next experiment. The remaining 3 groups of rats continued to be tested lung tissue pathology, Ashcroft scores, alveolar septal thickening measurement and the expression of pro-caspase 3, cleaved caspase 3, Bcl-2 and Bax of lung tissue.RESULTS The high dose of bicyclol group had the highest survival rate in all model groups(P<0.05). So the experiment was continued in the high dose of bicyclol group(bicyclol group). Compared to the model group, the degree of alveolar structure destruction and pulmonary interstitial fibrosis, pulmonary fibrosis Ashcroft's scoring were significantly reduced in bicyclol group(P<0.01), and the alveolar septal thickening was significantly thinner(P<0.01) and the expression of the Bax and cleaved caspase 3 decreased significantly (P<0.01), but the Bcl-2 was increased(P<0.01).CONCLUSION Bicyclol have significant protect effcet on BPF rats, the potential mechanism may be related to interfere with Bcl-2, Bax and cleaved caspase 3 to influence cell apoptosis for improving pulmonary fibrosis.