目的:观察蒙药额尔敦-乌日勒对斑马鱼心脏损伤后再生作用及其可能作用机制,验证其治疗的有效性,为进一步研究蒙药额尔敦-乌日勒提供实验依据。方法:利用转基因鱼系Tg(vmhc:mCherry-NTR)经甲硝唑(MTZ)处理后建立心室损伤模型,把90只受精3 d(3 dpf, days post fertilization)的斑马鱼胚胎随机分为对照组(DMSO,n=30)和心肌消融组(MTZ, n=30)以及心室损伤后额尔敦-乌日勒治疗组(MTZ+EW, n=30),治疗组在MTZ处理后24 h(24 hpt, 24 hour post treatment)用蒙药额尔敦-乌日勒混悬液以25 μg/mL治疗。3组在72 hpt检测细胞增殖,用共聚焦显微镜观察细胞增殖情况并定量分析,同时应用RT-qPCR分析一氧化氮合酶(NOS)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)的表达量。结果:治疗组斑马鱼胚胎经过蒙药额尔敦-乌日勒治疗后,心肌损伤后的再生修复比例明显上升,且再生心肌细胞的增殖速度较对照组加快、炎症因子表达量明显低于对照组。结论:蒙药额尔敦-乌日勒能够促进斑马鱼胚胎心肌细胞的修复再生,并促进心肌细胞的增殖,抑制心室损伤后的炎症反应。
林玉凤
,
赵蕊
,
陈向辉
,
朱伟
,
李晓锋
,
谢雅彬
,
谢伟
,
巴德仁贵
,
姜树原
,
刘晓蕾
,
邵国
,
白海花
,
贾小娥
. 蒙药额尔敦-乌日勒对心肌损伤的修复作用及机制探讨*[J]. 包头医学院学报, 2023
, 39(8)
: 1
-5
.
DOI: 10.16833/j.cnki.jbmc.2023.08.001
Objective: To observe the regenerative effect of Mongolian medicine Eerdun Wurile (EW) on zebrafish heart injury and its possible mechanism, and provide experimental basis for further research on Mongolian medicine Eerdun Wurile. Methods: The animal model of ventricular injury was established using the transgenic line Tg (vmhc: mCherry) treated with metronidazole (MTZ). The zebrafish embryos at 3 dpf(days post fertilization) were randomly divided into the control group (DMSO group,n=30), the experimental myocardial ablation group (MTZ group, n=30) and the Eerdun Wurile treatment group (MTZ+EW, n=30) after ventricular injury. Three groups were treated with 25 ug/ml Eerdun Wurile, a Mongolian medicine, after MTZ treatment for 24 hours. Three groups were tested for cell proliferation at 72 hpt. Cell proliferation were observed with confocal microscope and quantitatively analyzed. At the same time, NOS, iNOS, TNF-α, IL-1β and IL-6 were analyzed with real time qPCR. Results: After the treatment with Mongolian medicine Erden-Uhelle, the proportion of regeneration and repair after myocardial injury was significantly increased in the treatment group. And the proliferation of regenerated myocardial cells was enhanced in Eerdun Wurile treated group. The expression of inflammatory factors was significantly lower than that of the control group. Conclusion: Mongolian medicine Eerdun Wurile can promote the repair and regeneration of zebrafish embryonic cardiac muscle cells, promote the proliferation of cardiac muscle cells, and inhibit the inflammatory reaction after zebrafish embryonic ventricular injury.
[1] Kapur NK, Thayer KL, Zweck E.Cardiogenic shock in the setting of acute myocardial infarction[J].Methodist Debakey Cardiovasc J, 2020,16(1):16-21.
[2] Giacca M.Cardiac regeneration after myocardial infarction: an approachable goal[J].Curr Cardiol Rep, 2020,22(10):122.
[3] Khyeam S, LeeS, Huang GN.Genetic, epigenetic, and post-transcriptional basis of divergent tissue regenerative capacities among vertebrates[J].Adv Genet (Hoboken), 2021,2(2):e10042.
[4] Matrone G, Tucker CS, Denvir MA.Cardiomyocyte proliferation in zebrafish and mammals: lessons for human disease[J].Cell Mol Life Sci, 2017,74(8):1367-1378.
[5] 苏宁巴雅尔.蒙药新额尔敦-乌日勒防治心脑血管疾病疗效观察[J].北方药学, 2013, 10(3): 13-14.
[6] 张红霞, 苏和, 李汉青,等.蒙药“新额尔敦-乌日勒”对大鼠心肌缺血再灌注损伤的影响[Z].内蒙古自治区:内蒙古自治区国际蒙医医院,2016.
[7] Gonzalez -Rosa JM, MartinV, Peralta M, et al.Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish[J].Development, 2011,138(9):1663-1674.
[8] Xie FJ, Xu SS, Lu YY, et al.Metformin accelerates zebrafish heart regeneration by inducing autophagy[J].NPJ Regen Med, 2021,6(1):62.
[9] Xu SS, Webb SE, Lau TCK, et al.Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration[J].Sci Rep, 2018,8:7199.
[10] Bevan L, Lim ZW, Venkatesh B, et al.Specific macrophage populations promote both cardiac scar deposition and subsequent resolution in adult zebrafish[J].Cardiovasc Res, 2020,116(7):1357-1371.
[11] Simoes FC, Cahill TJ, Kenyon A, et al.Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair[J].Nat Commun, 2020,11(1):600.
[12] 策力木格, 松林, 刘梦娇, 等.蒙医药特色与发展思路[J].中国中医药图书情报杂志, 2016, 40(6): 4-9.