基于自噬探讨养阴益气方干预博来霉素诱导的大鼠特发性肺纤维化作用机制OA
Exploration on the Mechanism of Yangyin Yiqi Prescription in Bleomycin-induced Idiopathic Pulmonary Fibrosis in Rats Based on Autophagy
目的 观察养阴益气方对博来霉素诱导的大鼠肺纤维化的影响,基于自噬探讨其改善特发性肺纤维化的作用机制.方法 采用气管插管滴注盐酸博来霉素(3 mg/kg)建立肺纤维化大鼠模型,将大鼠随机分为空白组、模型组、养阴益气方组、吡非尼酮组、泼尼松组.空白组滴注等量生理盐水.造模次日起各组分别予相应药物灌胃,空白组和模型组予等体积生理盐水灌胃,每日1次,连续28 d.无创呼吸机检测大鼠最大呼气流速(PEF)、潮气量(VT),HE染色、Masson染色观察肺组织形态,Western blot检测肺组织LC3BⅡ/Ⅰ、Beclin-1、p62、基质金属蛋白酶(MMP)7蛋白表达,RT-PCR检测肺组织LC3B、Beclin-1、p62 mRNA表达.结果 与空白组比较,模型组大鼠PEF、VT明显降低(P<0.01),肺泡壁增厚变形,肺泡腔缩小或消失,炎性细胞浸润明显,出现大量胶原纤维沉积,肺泡炎评分和肺纤维化评分明显升高(P<0.01),肺组织LC3BⅡ/Ⅰ、Beclin-1蛋白表达降低,p62、MMP7蛋白表达升高(P<0.01),LC3B、Beclin-1 mRNA表达降低,p62 mRNA表达升高(P<0.01);与模型组比较,养阴益气方组大鼠PEF、VT明显升高(P<0.01),肺组织炎性细胞浸润减轻,胶原纤维沉积减少,肺泡炎评分和肺纤维化评分明显降低(P<0.01),肺组织LC3BⅡ/Ⅰ、Beclin-1蛋白表达升高,p62、MMP7蛋白表达降低(P<0.05,P<0.01),LC3B、Beclin-1 mRNA表达升高,p62 mRNA表达降低(P<0.05,P<0.01).结论 养阴益气方可能通过上调LC3BⅡ/Ⅰ、Beclin-1,下调p62、MMP7表达减轻肺泡炎症,延缓胶原纤维产生与堆积,从而减缓特发性肺纤维化进程.
Objective To observe the effects of Yangyin Yiqi Prescription on rats with pulmonary fibrosis induced by bleomycin;To explore the mechanism by which Yangyin Yiqi Prescription improving idiopathic pulmonary fibrosis through autophagy.Methods The rat model of idiopathic pulmonary fibrosis was established by bleomycin intratracheal instillation.The rats were randomly divided into blank group,model group,Yangyin Yiqi Prescription group,pirfenidone group and prednisone group.From the next day after modeling,each group was given corresponding drugs by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 28 days.The maximum expiratory flow(PEF)and volume of tidal(VT)were detected by noninvasive ventilator,the morphology of lung tissue was observed by HE staining and Masson staining,the protein expressions of LC3BⅡ/Ⅰ,Beclin-1,p62 and MMP7 in lung tissue were detected by Western blot,the mRNA expressions of LC3B,Beclin-1 and p62 in lung tissue were detected by RT-PCR.Results Compared with the blank group,PEF and VT in the model group were significantly decreased(P<0.01),the alveolar wall thickened and deformed,the alveolar cavity narrowed or disappeared,the inflammatory cell infiltration was obvious,a large number of collagen fibers were deposited,and the alveolitis score and pulmonary fibrosis score significantly increased(P<0.01);the protein expressions of LC3BⅡ/Ⅰ and Beclin-1 in lung tissue decreased,while the protein expressions of p62 and MMP7 increased(P<0.01),the mRNA expressions of LC3B and Beclin-1 decreased,while the expression of p62 mRNA increased(P<0.01).Compared with the model group,PEF and VT in Yangyin Yiqi Prescription group significantly increased(P<0.01),inflammatory cell infiltration in lung tissue was reduced,collagen fiber deposition was reduced,alveolitis score and pulmonary fibrosis score significantly decreased(P<0.01);the protein expressions of LC3BⅡ/Ⅰ and Beclin-1 in lung tissue increased,while the protein expressions of p62 and MMP7 decreased(P<0.05,P<0.01),the mRNA expressions of LC3B and Beclin-1 increased,while the mRNA expression of p62 decreased(P<0.05,P<0.01).Conclusion Yangyin Yiqi Prescription may alleviate alveolar inflammation by up-regulating LC3BⅡ/Ⅰ and Beclin-1,down-regulating the expressions of p62 and MMP7,and delaying the production and accumulation of collagen fibers,in order to slowing down the progression of idiopathic pulmonary fibrosis.
李辉;孟丽红;薛晓明;杨硕;谢地;王梦真;吴敏;杨卓敏;王晋煴
山西中医药大学,山西 太原 030000山西省中医院,山西 太原 030012山西省中医院,山西 太原 030012山西省中医院,山西 太原 030012山西省中医院,山西 太原 030012山西中医药大学,山西 太原 030000山西中医药大学,山西 太原 030000山西中医药大学,山西 太原 030000山西中医药大学,山西 太原 030000
医药卫生
特发性肺纤维化养阴益气方自噬p62大鼠
idiopathic pulmonary fibrosisYangyin Yiqi Prescriptionautophagyp62rats
《中国中医药信息杂志》 2026 (1)
64-69,6
国家自然科学基金(82205079)山西省基础研究计划(202203021212068)山西省人社厅博士基金项目(2023年)
评论