丹参酮ⅡA及苦参碱组方对脂多糖致小鼠急性肺损伤的协同保护作用  

Synergistic protection of tanshinone IIA and matrine on lipopolysaccharide-induced acute lung injury in mice

作　　者：熊欢庆 李玉娟 陈键 刘刚 李志超 金发光 Xiong Huanqing;Li Yujuan;Chen Jian;Liu Gang;Li Zhichao;Jin Faguang(Department of Respiratory and Critical Care Medicine,The Second Affiliated Hospital of Air Force Medical University,Xi′an 710038,China)

机构地区：[1]空军军医大学第二附属医院呼吸与危重症医学科,西安710038

出　　处：《中华肺部疾病杂志（电子版）》2023年第4期455-459,共5页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：国家自然科学基金资助项目(82270084)。

摘　　要：目的 分析丹参酮ⅡA(tanshinone ⅡA, TⅡA)与苦参碱(matrine, MAT)组合用药对脂多糖(lipopolysaccharide, LPS)致小鼠急性肺损伤(acute lung injury, ALI)的预防及治疗作用,探讨作用机制。方法 选择60只雄性C57小鼠,随机分为五组:对照组,LPS组,TⅡA+LPS组(TⅡA组),MAT+LPS组(MAT组),TⅡA+MAT+LPS组(TⅡA+MAT组),每组12只。TⅡA组给予TⅡA 10 mg/kg剂量灌胃,MAT组给予MAT 40 mg/kg灌胃,TⅡA+MAT组给予TⅡA 10 mg/kg+MAT 40 mg/kg灌胃,灌胃3 d,对照组及LPS组用同等体积的无菌生理盐水灌胃处理相同时间。末次给药1 h后除对照组外每组给予LPS 5 mg/kg腹腔注射行急性肺损伤造模,对照组注射同等体积的无菌生理盐水。造模6 h后,取肺组织,HE染色观察肺组织形态学改变,测定湿/干重比值(W/D),ELISA法测定肺泡灌洗液中肿瘤坏死因子-α(TNF-α)、白介素-1(IL-1)、白介素-6(IL-6),试剂盒法测定肺组织匀浆中髓过氧化物酶(MPO)活力及肺泡灌洗液(BALF)中蛋白含量。结果 形态学观察表明LPS组肺组织明显充血、水肿,有大量炎性细胞浸润,在TⅡA组、MAT组、TⅡA+MAT组内毒素致肺损伤减轻,TⅡA+MAT组表现明显,肺W/D比值降低(P<0.05)。单独应用TⅡA或MAT时肺泡灌洗液中IL-1、IL-6、TNF-α有不同程度下降(P>0.05),TⅡA+MAT组肺泡灌洗液中TNF-α、IL-1、IL-6较LPS相应时相点下降(P<0.05)。BALF中蛋白浓度LPS组较对照组升高,应用TⅡA或MAT后有不同程度下降(P<0.05),TⅡA+MAT组中蛋白浓度较LPS组降低(P<0.01)。肺组织匀浆MPO活力LPS组较对照组升高,单独应用TⅡA或MAT有轻度下降,无统计学意义(P>0.05),TⅡA+MAT组较LPS组MPO活力降低(P<0.05)。结论 丹参酮ⅡA及苦参碱能减轻LPS致小鼠急性肺损伤,两者配合使用效果较单药使用效果佳。Objective To observe the preventive and therapeutic effects of tanshinone IIA(TIIA)and matrine(MAT)in the prevention and treatment of lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice,and to preliminarily explore its mechanism.Methods Sixty male C57 mice were randomly divided into five groups:control group,LPS group,TIIA+LPS group(TIIA group),MAT+LPS group(MAT group),TIIA+MAT+LPS group(TIIA+MAT group),with 12 animals in each group.Among them,TIIA group was given TIIA 10 mg/kg dose of gavage,MAT group was given MAT 40 mg/kg gavage,TIIA+MAT group was given TIIA 10 mg/kg+MAT 40 mg/kg gavage for a total of three days,and the control group and LPS group were treated with the same volume of sterile normal saline for the same time.1 h after the last dose,except for the control group,all groups were given LPS 5 mg/kg intraperitoneal injection for acute lung injury modeling,and the control group was injected with the same volume of sterile normal saline.After 6 hours of molding,lung tissue was taken and HE staining was used to observe the morphological changes of lung tissue,the wet/dry weight ratio(W/D)was determined,tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),interleukin-6(IL-6)in bronchoalveolar lavage fluid was determined by ELISA method,and myeloperoxidase(MPO)activity and protein content in bronchoalveolar lavage fluid(BALF)in lung tissue homogenate was determined by kit method.Results Morphological observations showed that the lung tissue in the LPS group was significantly hyperemic and edematous,and there was a large number of inflammatory cell infiltrates,while the lung damage caused by endotoxin in the TIIA,MAT group and TIIA+MAT group was reduced,especially in the TIIA+MAT group,and the lung W/D ratio was reduced(P<0.05).When TIIA or MAT was applied alone,IL-1,IL-6 and TNF-αin alveolar lavage solution decreased to varying degrees,but there was no significant significance(P>0.05),and the concentrations of TNF-α,IL-1 and IL-6 in alveolar lavage solution in the TIIA+MAT group decreased signi

关 键 词：急性肺损伤 丹参酮 苦参碱 炎症 

分 类 号：R563[医药卫生—呼吸系统]