益气活血方对脂多糖致急性肺损伤大鼠肺气血屏障功能的影响OA北大核心CSTPCD
Effect of Yiqi Huoxue Formula on pulmonary alveolar-capillary barrier function in the rat of acute lung injury induced by lipopolysaccharide
目的 研究益气活血方对脂多糖诱导的急性肺损伤(ALI)大鼠肺气血屏障功能的影响并探讨其作用机制.方法 将SPF级雄性SD大鼠 60 只按随机数字表法分成假手术组、模型组、地塞米松组(5 mg/kg)和益气活血方低、中、高剂量(3.6、7.2、14.4 g/kg)组,每组 10 只.除假手术组大鼠气管内滴注生理盐水外,其余各组均滴注脂多糖(5mg/kg)制备ALI模型.地塞米松组和益气活血方各组大鼠给予相应药液灌胃,假手术组和模型组给予生理盐水灌胃,1 次/d,连续 7 d.于末次给药12 h后收集标本,观察各组大鼠肺组织病理改变,测定肺干湿重比值、支气管肺泡灌洗液(BALF)中总蛋白浓度,免疫荧光染色检测闭锁小带蛋白 1(ZO-1)表达,蛋白质印迹法检测闭锁蛋白(Occludin)、水通道蛋白(AQP)-1 和AQP-5 蛋白表达.结果 与假手术组比较,模型组大鼠肺损伤评分、肺干湿重比值和BALF中总蛋白浓度均升高(P<0.01),而益气活血方中、高剂量组较模型组均降低(P<0.05,P<0.01);与假手术组比较,模型组大鼠肺组织中 ZO-1、Occludin、AQP-1、AQP-5 蛋白表达明显下降(P<0.01),而益气活血方中、高剂量组均高于模型组(P<0.01).结论 益气活血方能够改善脂多糖诱导的ALI大鼠肺气血屏障功能障碍,作用机制与其上调紧密连接蛋白(ZO-1、Occludin)和水通道蛋白(AQP-1、AQP-5)表达有关.
Objective This study aims to reveal the effects of the Yiqi Huoxue Formula(YQHXF)on the function of the pulmonary alveolar-capillary barrier in rats with acute lipopolysaccharide-induced lung injury and to explore the potential mechanism.Methods Sixty adult male SD rats were randomly assigned to the sham operation,model,dexamethasone(5 mg/kg,gavage),Yiqi Huoxue Formula low-dose(3.6 g/kg,gavage),medium-dose(7.2 g/kg,gavage)and high-dose(14.4 g/kg,gavage)groups.The rats in the sham group received intratracheal instillation of normal saline,and those in other groups received intratracheal instillation of lipopolysaccharide(LPS,5 mg/kg)for the modeling of ALI.The rats in the sham and model groups were administered normal saline by gavage,and those in the other groups were administered the corresponding drugs once a day for 7 days.Specimens were collected 12 h after the last administration.Pathological changes in lung tissue were observed under a light microscope.The wet/dry weight ratio of the lung and the total protein concentration in the bronchoalveolar lavage fluid(BALF)were measured.Immunofluorescence staining was used to measure the protein expression of zonula occludens-1(ZO-1).Western blotting was used to measure protein levels of occludin,aquaporin-1(AQP-1),and AQP-5.Results Compared with the sham group,the model group showed an increased histopathological score of the lung tissue,lung wet/dry weight ratio,and protein concentration in BALF(P<0.01).Yiqi Huoxue Formula medium-and high-dose groups were lower than those in the model group(P<0.05,P<0.01).Compared with the sham group,the model group downregulated the expression of ZO-1,occludin,AQP-1,and AQP-5(P<0.01).Yiqi Huoxue Formula medium-and high-dose groups upregulated the protein levels compared with the model group(P<0.01).Conclusion The findings suggest that the Yiqi Huoxue Formula can improve the dysfunction of the pulmonary alveolar-capillary barrier in the rat model of ALI induced by LPS,and its mechanism is related to regulating tight junction protein(ZO-1,occludin)and aquaporin(AQP-1,AQP-5)expression.
秦丽;向盈;李涵;李敏;齐小荣
中国人民解放军总医院第六医学中心中医医学部 北京 100853
中医学
急性肺损伤益气活血方肺气血屏障紧密连接蛋白水通道蛋白大鼠
acute lung injuryYiqi Huoxue Formulapulmonary alveolar-capillary barriertight junction proteinaquaporinrats
《北京中医药大学学报》 2024 (012)
1702-1709 / 8
国家自然科学基金项目(No.81303131);解放军总医院第六医学中心创新培育基金项目(No.CXPY202214) National Natural Science Foundation of China(No.81303131)
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