CAJ | 학술논문

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(matrix metalloproteinase-2,MMP-2)和金属蛋白酶组织抑制剂 1(tissue inhibitor of metalloproteinase-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-1 mRNA 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-1 mRNA 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-1 mRNA 基因转录水平均显著增高,尤以 MMP-2 mRNA 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-1 mRNA 的基因转录表达继续增高,但 TIMP-1 mRNA 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-1 mRNA 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-1 mRNA 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-1 mRNA 的表达来抑制 MMP-2 mRNA 表达水平,从而起到延缓肺纤维化的作用.
목적:관찰박래매소치폐섬유화대서폐조직중기질금속단백매 2(matrix metalloproteinase-2,MMP-2)화금속단백매조직억제제 1(tissue inhibitor of metalloproteinase-1,TIMP-1)mRNA 적표체,탐토중약복방삼룡전제방치대서폐섬유화적작용궤제.방법:230 지건강웅성 Wistar 대서수궤분위정상대조조、모형조、발니송조화삼룡전제저、중、고제량조,채용기관내주입박래매소적방법건립 Wistar 대서폐섬유화모형.정상대조조화모형조대서제 2 일기매일여생리염수관위,기여각조대서안배호적삼룡전제이등용약품관위.소목소-이홍염색화 Masson 염색관찰불동시간점대서폐조직병리변화,이평개모형시부성공.역전록취합매련반응검측대서폐조직 MMP-2 화TIMP-1 mRNA 적표체수평.결과:각조대서폐조직재각개시간점균유 MMP-2 화 TIMP-1 mRNA 표체.여정상대조조대서비교,모형조대서재제 7 천시 MMP-2 화 TIMP-1 mRNA 기인전록수평균현저증고,우이 MMP-2 mRNA 증가명현,차이균유통계학의의(P<0.05 혹 P<0.01);재제 14 천시,MMP-2 화 TIMP-1 mRNA 적기인전록표체계속증고,단 TIMP-1 mRNA 증가경현저,차이균유통계학의의(P<0.05 혹 P<0.01);제 28 천시,MMP-2 이유소하강,단 TIMP-1 mRNA 표체잉지속성증고,차이균유통계학의의(P<0.05 혹 P<0.01).여모형조대서비교,치료조대서제 7 천 MMP-2 화 TIMP-1 mRNA 기인전록수평강저,우기시 MMP-2 적표체강저경명현,제 28 천시저충강저작용잉지속존재,이삼룡전제중제량조대서표현최명현,차이균유통계학의의(P<0.05혹P<0.01).결론:삼룡전제가능시통과상조 TIMP-1 mRNA 적표체래억제 MMP-2 mRNA 표체수평,종이기도연완폐섬유화적작용.
Objective:To observe the expressions of matrix metalloproleinase-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-2and 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 inc reasing(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.