摘要
目的探究黄芪注射液对肺纤维化的干预作用及可能机制。方法利用TargetScanHuman网站预测miR-29a-3p的靶基因。气管内注入博来霉素以构建肺纤维化大鼠模型。大鼠随机分为假手术组、博来霉素组、吡非尼酮组、黄芪注射液低剂量组和高剂量组,分别予生理盐水腹腔注射、吡非尼酮灌胃、黄芪注射液低剂量和高剂量腹腔注射。连续给药28 d后,用肺功能仪测定肺通气指标,Masson染色和天狼猩红染色观察肺组织镜下胶原沉积情况,实时定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测肺组织miR-29a-3p和Ⅰ型胶原α1链基因(type I alpha 1 chain collagen gene,COL1A1)mRNA表达量。结果miR-29a-3p与COL1A1之间具有良好的靶向调控关系。与假手术组相比,博来霉素组大鼠肺动态顺应性(Cydn)显著下降,而吸气相气道阻力(RL)、呼气相气道阻力(Re)显著提高,肺组织COL1A1 mRNA表达显著提高且镜下胶原沉积明显增多(P<0.01)。与博来霉素组相比,各给药组Cydn显著提高,而RL、Re显著下降(P<0.01),黄芪低、高剂量组用力肺活量(FVC)显著提高(P<0.05,P<0.01),各给药组肺组织miR-29a-3p表达均有上升趋势,但仅黄芪低剂量组与博来霉素组比较差异有显著统计学意义(P<0.01),各给药组肺组织COL1A1 mRNA表达显著下降且镜下胶原沉积明显减少(P<0.01)。结论黄芪注射液能够通过miR-29a-3p/COL1A1信号轴减少肺内胶原沉积并改善博来霉素诱导的肺纤维化大鼠模型的肺通气障碍。
Objective To explore the effect of Huangqi Injection(黄芪注射液)on pulmonary fibrosis and its potential mechanism.Method Target genes of miR-29a-3p were predicted by using TargetScanHuman database.The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin.All rats were randomly divided into sham operation group,bleomycin group,pirfenidone group,Huangqi Injection low-dose group and Huangqi Injection high-dose group.The groups were given normal saline by intraperitoneal injection,pirfenidone intragastric injection,low-dose and high-dose Huangqi Injection by intraperitoneal injection respectively.After 28 days of continuous administration,the lung ventilation index was measured by pulmonary function instrument.Masson staining and Sirius red staining were performed to observe the microscopic collagen deposition,and real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect mRNA relative expression levels of miR-29a-3p and type I alpha 1 chain collagen gene(COL1A1)in lung tissue.Results MiR-29a-3p and COL1A1 had a good targeted regulatory relationship.Compared with that in the sham operation group,the dynamic lung compliance(Cydn)in bleomycin group was significantly decreased,while inspiratory airway resistance(RL),expiratory airway resistance(Re)were significantly increased,mRNA expressions of COL1A1 were significantly up-regulated,and microscopic collagen deposition was significantly increased(P<0.01).Compared with those in the bleomycin group,Cydn in each administration group was significantly increased,while RL and Re were significantly decreased(P<0.01).Forced vital capacity(FVC)in Huangqi Injection low-dose and high-dose groups were significantly increased(P<0.05,P<0.01).MiR-29a-3p expression in lung tissues of each administration group showed an upward trend,however,only the Huangqi Injection low-dose group and bleomycin group had sig-nificant difference(P<0.01).The mRNA expression of COL1A1 in lung tissues of each administration group were significantly down-regulated,and the microscopic collagen deposition was significantly decreased(P<0.01).Conclusion Huangqi Injection can reduce collagen deposition in lung tissue through miR-29a-3p/COL1A1 pathway and improve pulmonary ventilation disorder in bleomycin-induced pulmonary fibrosis rat model.
作者
周飘
杜婧
吴程
周芮
安丽萍
王飞
杜全宇
ZHOU Piao;DU Jing;WU Cheng;ZHOU Rui;AN Liping;WANG Fei;DU Quanyu(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,Sichuan,China)
出处
《中华中医药学刊》
CAS
北大核心
2023年第3期107-110,I0026,共5页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(82174347)
成都中医药大学“杏林学者”学科人才科研提升计划项目(BSH2019022)。
