【摘要】 目的:观察博来霉素致肺纤维化大鼠肺组织中基质金属蛋白酶2(matrixmetalloproteinase-2,MMP-2)和金属蛋白酶组织抑制剂1(tissue inhibitor of metallo proteinase-1,TIMP-1)mRNA的表达,探讨中药复方参龙煎剂防治大鼠肺纤维化的作用机制。方法:230只健康雄性Wistar大鼠随机分为正常对照组、模型组、泼尼松组和参龙煎剂低、中、高剂量组,采用气管内注入博来霉素的方法建立Wistar大鼠肺纤维化模型。正常对照组和模型组大鼠第2日起每日予生理盐水灌胃,其余各组大鼠按配好的参龙煎剂以等容药品灌胃。苏木素-伊红染色和Masson染色观察不同时间点大鼠肺组织病理变化,以评价模型是否成功。逆转录聚合酶链反应检测大鼠肺组织MMP-2和TIMP-1mRNA的表达水平。结果:各组大鼠肺组织在各个时间点均有MMP-2和TIMP-1mRNA表达。与正常对照组大鼠比较,模型组大鼠在第7天时MMP-2和TIMP-1mRNA基因转录水平均显著增高,尤以MMP-2mRNA增加明显,差异均有统计学意义(P<0.05或P<0.01);在第14天时,MMP-2和TIMP-1mRNA的基因转录表达继续增高,但TIMP-1mRNA增加更显著,差异均有统计学意义(P<0.05或P<0.01);第28天时,MMP-2已有所下降,但TIMP-1mRNA表达仍持续性增高,差异均有统计学意义(P<0.05或P<0.01)。与模型组大鼠比较,治疗组大鼠第7天MMP-2和TIMP-1mRNA基因转录水平降低,尤其是MMP-2的表达降低更明显,第28天时这种降低作用仍持续存在,以参龙煎剂中剂量组大鼠表现最明显,差异均有统计学意义(P<0.05或P<0.01)。结论:参龙煎剂可能是通过上调TIMP-1mRNA的表达来抑制MMP-2mRNA表达水平,从而起到延缓肺纤维化的作用。更多还原

【Abstract】 Objective:To observe the expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rats with pulmonary fibrosis (PF) induced by bleomycin,and to explore the mechanisms of Shenlong Decoction in preventing and treating PF.Methods:A total of 230 Wistar rats were divided into normal control group,untreated group,prednisone group,and low-,medium-and high-dose Shenlong Decoction groups.Wistar rats were intratracheally injected with bleomycin to induce PF.From the 2nd day,rats in the normal control and untreated groups were lavaged with normal saline (NS),and rats in the other groups were lavaged with prepared Shenlong Decoction by the same amount.Hemotoxylin-eosin (HE) staining and Masson staining were used to observe pathological changes in lung tissue at different time points,and to evaluate whether the model was successfully induced.Expressions of MMP-2 and TIMP-1 mRNAs in rats’ lung tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR).Results:Expressions of MMP-2 and TIMP-1 mRNAs in lung tissue of rats were observed from all groups at each time point.In comparison with the normal control group,on the 7th day,the transcription levels of MMP-2 and TIMP-1 mRNAs,especially the former,of the untreated group increased significantly (P<0.05 or P<0.01).On the 14th day,the transcription levels of MMP-2 and TIMP-1 mRNAs kept rising,especially the latter (P<0.05 or P<0.01).On the 28th day,the transcription level of MMP-2 decreased a little,while the transcription level of TIMP-1 mRNA did not stop increasing (P<0.05 or P<0.01).Compared with the untreated group,decrease of the transcription levels of MMP-2 and TIMP-1 mRNAs were observed in the treatment groups,especially the former,and this effect continued to the 28th day with the medium-dose Shenlong Decoction group decreasing most obviously (P<0.05 or P<0.01).Conclusion:Shenlong Decoction may inhibit the expression of MMP-2 mRNA by up-regulating the expression of TIMP-1 mRNA so as to slow the progression of PF.更多还原