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中华肺部疾病杂志(电子版) ›› 2023, Vol. 16 ›› Issue (04) : 455 -459. doi: 10.3877/cma.j.issn.1674-6902.2023.04.001

论著

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
熊欢庆, 李玉娟, 陈键, 刘刚, 李志超, 金发光()   
  1. 710038 西安,空军军医大学第二附属医院呼吸与危重症医学科
  • 收稿日期:2023-01-17 出版日期:2023-08-25
  • 通信作者: 金发光
  • 基金资助:
    国家自然科学基金资助项目(82270084)

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

Huanqing Xiong, Yujuan Li, Jian Chen, Gang Liu, Zhichao Li, Faguang Jin()   

  1. Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Air Force Medical University, Xi′an 710038, China
  • Received:2023-01-17 Published:2023-08-25
  • Corresponding author: Faguang Jin
引用本文:

熊欢庆, 李玉娟, 陈键, 刘刚, 李志超, 金发光. 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[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 455-459.

Huanqing Xiong, Yujuan Li, Jian Chen, Gang Liu, Zhichao Li, Faguang Jin. Synergistic protection of tanshinone IIA and matrine on lipopolysaccharide-induced acute lung injury in mice[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2023, 16(04): 455-459.

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-α in 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 significantly compared with the corresponding phase points of LPS (P<0.05). The protein concentration in the LPS group in BALF was significantly higher than that in the control group, and decreased to varying degrees after TIIA or MAT (P<0.05), but the protein concentration in the TIIA+ MAT group was significantly lower than that in the LPS group (P<0.01). The MPO viability LPS group of lung tissue homogenate was significantly higher than that of the control group, and there was a slight decrease in TIIA or MAT alone, but there was no significant (P>0.05), while the TIIA+ MAT group was significantly lower than that in the LPS group. Statistically significant (P<0.05).

Conclusion

Tanshinone IIA and matrine can reduce acute lung injury caused by LPS, but the combination effect of the two is better than that of single agent.

图1 每组W/D值比较;与对照组比较:*P<0.05,**P<0.01;与LPS组比较:#P<0.05,##P<0.01
图2 每组生存率比较。对照组vs. LPS组:P<0.01;LPS组vs. TIIA组:P>0.05;LPS组vs. MAT组:P>0.05;LPS组vs. TIIA+MAT组:P<0.01
图3 每组小鼠HE结果。注:A:对照组;B:TIIA+MAT组;C:LPS组;D:TIIA组;E:MAT组
图4 每组小鼠BALF中蛋白浓度。与对照组比较:*P<0.05,**P<0.01;与LPS组比,#P<0.05,##P<0.01
图5 每组肺泡灌洗液IL-1、IL-6、TNF-α结果。注:A:每组小鼠BALF中IL-1浓度情况。与对照组比较:*P<0.05,**P<0.01;与LPS组比,#P<0.05,##P<0.01;B:每组小鼠BALF中IL-6浓度情况。与对照组比较:*P<0.05,**P<0.01;与LPS组比,#P<0.05,##P<0.01;C:每组小鼠BALF中TNF-α浓度情况。与对照组比较:*P<0.05,**P<0.01;与LPS组比,#P<0.05,##P<0.01
图6 每组小鼠BALF中MPO活力情况。与对照组比较:*P<0.05,**P<0.01;与LPS组比,#P<0.05,##P<0.01
1
金发光. 急性肺损伤的诊治研究现状及进展[J/CD]. 中华肺部疾病杂志(电子版), 2013, 6(1): 1-3.
2
Arcaroli J, Yum H K, Kupfner J, et al. Role of p38 MAP kinase in the development of acute lung injury[J]. Clin Immunol, 2001, 101(2): 211-219.
3
Huppert L, Matthay M, Ware L. Pathogenesis of acute respiratory distress syndrome[J]. Sem Respir Crit Care Med, 2019, 40(1): 31-39.
4
Reising CA, Chendrasekhar A, Wall PL, et al. Continuous dose furosemide as a therapeutic approach to acute respiratory distress syndrome (ARDS)[J]. J Surg Res, 1999, 82(1): 56-60.
5
杜冠华,张均田. 丹参现代研究概况与进展(续一)[J]. 医药导报2004, 23(6): 355-360.
6
Xu M, Dong MQ, Cao FL, et al. Tanshinone IIA reduces lethality and acute lung injury in LPS-treated mice by inhibition of PLA2 activity[J]. Eur J Pharmacol, 2009, 607(1-3): 194-200.
7
Lan X, Zhao J, Zhang Y, et al. Oxymatrine exerts organ-and tissue-protective effects by regulating inflammation, oxidative stress, apoptosis, and fibrosis: From bench to bedside[J]. Pharmacol Res, 2020, 151: 104541.
8
许 敏,李志超,董明清,等. 丹参酮IIA磺酸钠对脂多糖致小鼠急性肺损伤的预防与治疗作用及其机制[J]. 中国药理学通报2008, 24(4): 477-481.
9
Xu G L, Yao L, Rao S Y, et al. Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase[J]. J Ethnopharm, 2005, 98(1-2): 177-183.
10
Chen X, Wang Y, Xie X, et al. Heme oxygenase-1 reduces sepsis-induced endoplasmic reticulum stress and acute lung injury[J]. Media Inflamm, 2018, 2018: 9413876.
11
Van Lent PL, Van De Loo FA, Holthuysen AE, et al. Major role for interleukin 1 but not for tumor necrosis factor in early cartilage damage in immune complex arthritis in mice[J]. J Rheumatol, 1995, 22(12): 2250-2258.
12
Guo R, Li L, Su J, et al. Pharmacological activity and mechanism of tanshinone IIA in related diseases[J]. Drug Des Devel Ther, 2020, 14: 4735-4748.
13
Zhang W, Liu C, Li J, et al. Tanshinone IIA: New perspective on the anti-tumor mechanism of A traditional natural medicine[J]. Am J Chin Med, 2022, 50(1): 209-239.
14
Li J, Zheng Y, Li M X, et al. Tanshinone IIA alleviates lipopolysaccharide-induced acute lung injury by downregulating TRPM7 and pro-inflammatory factors[J]. J Cell Mol Med, 2018, 22(1): 646-654.
15
Zhao JY, Pu J, Fan J, et al. Tanshinone IIA prevents acute lung injury by regulating macrophage polarization[J]. J Integr Med, 2022, 20(3): 274-280.
16
Liu JY, Hu JH, Zhu QG, et al. Effect of matrine on the expression of substance P receptor and inflammatory cytokines production in human skin keratinocytes and fibroblasts[J]. Int Immunopharmacol, 2007, 7(6): 816-823.
17
Sun XY, Jia LY, Rong Z, et al. Research advances on matrine[J]. Front Chem, 2022, 10: 867318.
18
Zhang B, Liu ZY, Li YY, et al. Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice[J]. Eur J Pharm Sci, 2011, 44(5): 573-579.
19
Liou CJ, Lai YR, Chen YL, et al. Matrine attenuates COX-2 and ICAM-1 expressions in human lung epithelial cells and prevents acute lung injury in LPS-induced mice[J]. Mediat Inflamm, 2016, 2016: 3630485.
20
Li WW, Wang TY, Cao B, et al. Synergistic protection of matrine and lycopene against lipopolysaccharideinduced acute lung injury in mice[J]. Mol Med Rep, 2019, 20(1): 455-462.
21
Huang WC, Wu SJ, Tu RS, et al. Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells[J]. Food Funct, 2015, 6(6): 1960-1967.
22
Liou CJ, Huang YL, Huang WC, et al. Water extract of Helminthostachys zeylanica attenuates LPS-induced acute lung injury in mice by modulating NF-κB and MAPK pathways[J]. J Ethnopharmacol, 2017, 199: 30-38.
23
Tai H, Jiang X, Song N, et al. Tanshinone IIA combined with cyclosporine A alleviates lung apoptosis induced by renal ischemia-reperfusion in obese rats[J]. Front Med2021, 8: 617393.
24
Li WW, Wang TY, Cao B, et al. Synergistic protection of matrine and lycopene against lipopolysaccharide induced acute lung injury in mice[J]. Mol Med Rep, 2019, 20(1): 455-462.
25
Zhao P, Zhou R, Zhu XY, et al. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice[J]. Int J Mol Med, 2015, 36(3): 633-644.
26
Li H, Yang T, Fei Z. miR26a5p alleviates lipopolysaccharideinduced acute lung injury by targeting the connective tissue growth factor[J]. Mol Med Rep, 2021, 23(1): 5.
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