CAJ | 학술논문

目的：观察乌司他丁联合异甘草酸镁对博莱霉素（BLM）诱导的肺纤维化大鼠肺组织转化生长因子β1（TGF-β1）和结缔组织生长因子（CTGF）表达的影响。方法90只大鼠随机分为以下5组：BLM组、甲泼尼龙琥珀酸钠（MTH）组、乌司他丁（UTI）组、异甘草酸镁（MgIG）组、乌司他丁联合异甘草酸镁（UTI+MgIG）组，各18只。5组均以气管内注入BLM建立大鼠肺纤维化模型，造模成功24 h后，BLM组大鼠每日腹腔注射生理盐水，其余各组给予相应药物腹腔注射。每组分别于第7、14和28天处死6只，HE染色评价肺组织肺泡炎及纤维化程度，免疫组化测定肺组织TGF-β1和CTGF的表达水平。结果（1）药物干预各组肺泡炎及肺纤维化程度均较BLM组有所减轻，其中UTI+MgIG组第7、14天肺泡炎程度，第14、28天肺纤维化程度与BLM组差异有统计学意义（P<0.05）。（2）药物干预各组TGF-β1和CTGF的表达水平在各时间点均较同期BLM组有所降低；UTI+MgIG组TGF-β1的表达水平在第7、14天时明显低于UTI组和MgIG组，第28天时明显低于MTH组、UTI组和MgIG组（P<0.05）；UTI+MgIG组CTGF的表达水平在第7天时明显低于UTI组和MgIG组，第14、28天时明显低于MTH组、UTI组和MgIG组（P<0.05）。结论 UTI联合MgIG能减轻BLM诱导的大鼠肺泡炎及纤维化程度，其机制可能与下调TGF-β1和CTGF的表达有关。
목적：관찰오사타정연합이감초산미대박래매소（BLM）유도적폐섬유화대서폐조직전화생장인자β1（TGF-β1）화결체조직생장인자（CTGF）표체적영향。방법90지대서수궤분위이하5조：BLM조、갑발니룡호박산납（MTH）조、오사타정（UTI）조、이감초산미（MgIG）조、오사타정연합이감초산미（UTI+MgIG）조，각18지。5조균이기관내주입BLM건립대서폐섬유화모형，조모성공24 h후，BLM조대서매일복강주사생리염수，기여각조급여상응약물복강주사。매조분별우제7、14화28천처사6지，HE염색평개폐조직폐포염급섬유화정도，면역조화측정폐조직TGF-β1화CTGF적표체수평。결과（1）약물간예각조폐포염급폐섬유화정도균교BLM조유소감경，기중UTI+MgIG조제7、14천폐포염정도，제14、28천폐섬유화정도여BLM조차이유통계학의의（P<0.05）。（2）약물간예각조TGF-β1화CTGF적표체수평재각시간점균교동기BLM조유소강저；UTI+MgIG조TGF-β1적표체수평재제7、14천시명현저우UTI조화MgIG조，제28천시명현저우MTH조、UTI조화MgIG조（P<0.05）；UTI+MgIG조CTGF적표체수평재제7천시명현저우UTI조화MgIG조，제14、28천시명현저우MTH조、UTI조화MgIG조（P<0.05）。결론 UTI연합MgIG능감경BLM유도적대서폐포염급섬유화정도，기궤제가능여하조TGF-β1화CTGF적표체유관。
Objective To investigate the effects of ulinastatin (UTI) combined with magnesium isoglycyrrhizinate (MgIG) on the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tis?sue of rats with pulmonary fibrosis induced by bleomycin (BLM). Methods Ninety Wistar rats were randomly divided into five groups: BLM group, methylprednisolone (MTH) group, UTI group, MgIG group and UTI combined with MgIG (UTI+MgIG) group, n=18 for each group. The rat model of pulmonary fibrosis was established by injecting bleomycin through tra?chea in five groups. Twenty-four hours after treatment with BLM,rats were treated with normal saline every day in BLM group, and rats were treated by corresponding drugs in other groups. Six rats of each group were killed at the 7th,14th and 28th day respectively. The pathological changes of alveolitis and pulmonary fibrosis were evaluated by HE staining, and ex?pression levels of TGF-β1 and CTGF in lung tissues were detected by immunohistochemistry method. Results (1) Com?pared with BLM group, the degree of alveolitis and pulmonary fibrosis was reduced in other groups. There was significant dif?ference in alveolitis at the 7th and 14th day between UTI+MgIG group and BLM group. And there was significant difference in pulmonary fibrosis at the 14th and 28th day between UTI+MgIG group and BLM group (P<0.05). (2) Compared with BLM group, the expression levels of TGF-β1 and CTGF were decreased in other groups. In UTI+MgIG group, the expres?sion levels of TGF-β1 were significantly lower at the 7th and 14th day compared with those in UTI group and MgIG group, and which were significantly lower at the 28th day than those in MTH group, UTI group and MgIG group (P<0.05). The ex?pression levels of CTGF were significantly lower at the 7th day in UTI + MgIG group than those in UTI group and MgIG group, and which were significantly lower at the 14th and 28th day than those in MTH group, UTI group and MgIG group (P<0.05). Conclusion The combination of UTI and MgIG can alleviate alveolitis and fibrosis in BLM-induced pulmonary fibrosis rats, which might related with the down-regulation of TGF-β1 and CTGF expressions.