二十五味珍珠片对斑马鱼微血管功能的影响
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摘要
目的:探究二十五味珍珠片对斑马鱼微血管功能的改善作用。方法:分别采用花生四烯酸、辛伐他汀、普纳替尼诱导斑马鱼血栓模型,微血管缺失模型以及血管内皮损伤模型。二十五味珍珠片药物干预后,统计斑马鱼心输出量和血流速度,计算斑马鱼肠下血管面积和斑马鱼体节间血管直径,观察尾静脉血栓形成情况,评价二十五味珍珠片对血管内皮的保护作用以及对血栓生成的影响。结果:与模型组比较,二十五味珍珠片27. 8 mg·L~(-1)组心输出量显著性增加(P <0. 05),血流速度显著性增加(P <0. 01);与模型组比较,质量浓度为0. 11,0. 33,1 mg·L~(-1)的二十五味珍珠片干预后,斑马鱼肠下血管面积增加(P <0. 01);血管内皮损伤模型中,与模型组比较,33,100 mg·L~(-1)的二十五味珍珠片干预后,斑马鱼节间血管直径有明显增加(P <0. 05,P <0. 01);与模型组比较,质量浓度为100 mg·L~(-1)的二十五味珍珠片干预后,斑马鱼血栓发生率显著降低(P <0. 01)。结论:二十五味珍珠片可以改善微血管功能障碍,其作用机制可能与其减少血管内皮损伤促进其再生,改善微血管血流动力学作用减少血栓生成有关。
Objective: To explore the effect of Ershiwuwei Zhenzhu tablets( EZT) on microvascular function. Method: The zebrafish models of thrombosis,microvascular defect and vascular endothelial injury were induced by using arachidonic acid,simvastatin and ponatinib respectively,and treated with EZT,astragaloside or asprin. To evaluate the protective effect of EZT on vascular endothelium and its effect on thrombus formation,zebrafish heart output and blood flow velocity were counted,and the vascular area of the zebrafish intestine and the intervascular diameter were calculated. The thrombus in the tail vein was observed under microscope. Result:Compared with model group,EZT improved the cardiac output( P < 0. 05) and blood flow velocity( P < 0. 01) of zebrafish in thrombus model at a concentration of 27. 8 mg·L~(-1),and promoted angiogenesis in zebrafish at concentrations of 0. 11,0. 33,1 mg·L~(-1). Compared with the model group,the vascular diameter of the zebrafish internode was significantly increased at the concentrations of 33 mg·L~(-1)( P < 0. 05) and 100 mg·L~(-1)( P < 0. 01),and the incidence of zebrafish thrombosis was significantly reduced after EZT intervention at 100 mg·L~(-1)( P <0. 01). Conclusion: EZT could improve microvascular dysfunction,and its mechanism may be related to the reduction of vascular endothelial damage to promote its angiogenesis and the improvement of microvascular hemodynamics to reduce thrombus formation.
Objective: To explore the effect of Ershiwuwei Zhenzhu tablets( EZT) on microvascular function. Method: The zebrafish models of thrombosis,microvascular defect and vascular endothelial injury were induced by using arachidonic acid,simvastatin and ponatinib respectively,and treated with EZT,astragaloside or asprin. To evaluate the protective effect of EZT on vascular endothelium and its effect on thrombus formation,zebrafish heart output and blood flow velocity were counted,and the vascular area of the zebrafish intestine and the intervascular diameter were calculated. The thrombus in the tail vein was observed under microscope. Result:Compared with model group,EZT improved the cardiac output( P < 0. 05) and blood flow velocity( P < 0. 01) of zebrafish in thrombus model at a concentration of 27. 8 mg·L~(-1),and promoted angiogenesis in zebrafish at concentrations of 0. 11,0. 33,1 mg·L~(-1). Compared with the model group,the vascular diameter of the zebrafish internode was significantly increased at the concentrations of 33 mg·L~(-1)( P < 0. 05) and 100 mg·L~(-1)( P < 0. 01),and the incidence of zebrafish thrombosis was significantly reduced after EZT intervention at 100 mg·L~(-1)( P <0. 01). Conclusion: EZT could improve microvascular dysfunction,and its mechanism may be related to the reduction of vascular endothelial damage to promote its angiogenesis and the improvement of microvascular hemodynamics to reduce thrombus formation.
引文
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[21]郑乘龙.益气活血药对心梗大鼠冠脉微血管内皮损伤活性分子的调控机制研究[D].北京:北京中医药大学,2012.
[22]黄琨.益气活血中药对心梗大鼠冠脉微血管功能障碍及相关分子调控机制的研究[D].北京:北京中医药大学,2013.
[23]杜海波,麝香保心丸治疗微血管功能障碍的研究进展[J].世界最新医学信息文摘,2016,16(56):34-35.
[24] Lanza G A,Crea F. Primary coronary microvascular dysfunction:clinical presentation,pathophysiology,and management[J]. Circulation,2010,121(21):2317-2325.
[25]逯雯洁,王慧春,海平,等.高效液相色谱法同时测定二十五味珍珠丸中7种成分及其特征图谱[J].中国医院药学杂志,2016,36(21):1885-1890.
[26] Herrmann J, Kaski J C, Lerman A. Coronary microvascular dysfunction in the clinical setting:from mystery to reality[J]. Eur Heart J,2012,33(22):2771-2783.
[27]刘旭杰,秦烨,陈淑珍.吉西他滨对肺微血管内皮细胞的损伤及表没食子儿茶素没食子酸酯的保护作用[J].中国医药生物技术,2014,9(6):438-445.
[28]郭建友,霍海如,刘洪斌,等.桂皮醛对IL-1刺激下脑微血管内皮细胞COX-1、COX-2活性及释放PGE2的影响[J].中药药理与临床,2005,21(6):16-18.
[29] McGrath P,LI C Q,Zebrafish:a predictive model for assessing drug-induced toxicity[J]. Drug Discov Today,2008,13(9/10):394-401.
[30]高家荣,郭明飞,方朝晖,等.黄地安消胶囊对高糖高脂诱导的斑马鱼血管病变保护作用研究[J].中国中药杂志,2018,42(21):4317-4322.
[31]李晓稳,佟玲,李东翔,等.斑马鱼神经元损伤模型在养血清脑颗粒质量控制中的应用分析[J].中国实验方剂学杂志,2016,22(9):1-4.
[32]罗隽,梅雪,夏青,等.醋甘遂不同提取物对斑马鱼幼鱼的毒性[J].中国实验方剂学杂志,2018,24(4):160-166.
[2] Serne E H, Stehouwer C D, Maaten J C, et al.Microvascular function relates to insulin sensitivity and blood pressure in normal subjects[J]. Circulation,1999,99(7):896-902.
[3]何金孝,王炜中,张海锋,等.微血管功能在代谢综合征发生机制中的研究进展[J].心脏杂志,2016,28(2):234-236.
[4]宇妥·元丹贡布.四部医典[M].北京:人民卫生出版社,1983:216.
[5]国家药典委员会.中华人民共和国卫生部药品标准·藏药.第一册[S].北京:中华人民共和国卫生部,1995:140.
[6]吴洪福,耿排力.藏药研究现状及发展前景[J].中药材,2002,25(1):65-66.
[7]才让措,郭登海.藏药“二十五味珍珠丸”方解及功能浅述[J].中国民族民间医药,2012,21(7):1.
[8]王智森,赵献超,郑学军,等.二十五味珍珠丸治疗脑血栓后遗症的临床疗效观察[J].世界中西医结合杂志,2013,8(2):165-167.
[9]万高.藏药二十五味珍珠丸治疗脑血栓后遗症对疗效、神经功能缺损评分和日常生活活动能力的影响[J].临床医药文献电子杂志,2017,4(64):12630.
[10]周盛年,韩永涛,魏先森,等.藏药二十五味珍珠丸治疗缺血性脑卒中的临床研究[J].中西医结合心脑血管病杂志,2007,5(11):1063-1064.
[11]王智森,刘水娟,赵献超,等.藏诺牌二十五味珍珠丸治疗冠心病心绞痛临床疗效观察[J].中西医结合研究,2014,6(2):71-74.
[12]张黎明,刘生.二十五味珍珠丸对实验性脑缺血大鼠脑毛细血管通透性及脑含水量的影响[J].中国药房,2006,17(9):664-665.
[13]张勇,朱晓宇,郭胜亚,等.苯肼诱发建立斑马鱼血栓模型的方法[J].实验动物与比较医学,2015,35(1):27-31.
[14]王木兰,潘永明,金敏,等.斑马鱼血栓模型的建立与冠心宁片的干预作用[J].中国实验动物学报,2016,24(4):432-438.
[15] ZHANG Y,GUO S Y,ZHU X Y,et al. Arachidonic acid induced thrombosis in zebrafish larvae for assessing human anti-thrombotic drugs[J]. Jsm Cell Dev Biol,2017,5(1):1023.
[16]朱晓宇,郭胜亚,徐懿乔,等.安宫牛黄丸防治脑血管疾病作用研究[J].药物评价研究,2017,40(8):1067-1072.
[17] WANG C Y,TAO W Y, WANG Y D, et al.Rosuvastatin, identified from a zebrafish chemical genetic screen for antiangiogenic compounds,suppresses the growth of prostate cancer[J]. Eur Urol,2010,58(3):418-426.
[18]张亚楠,孙继红,黄新益,等.普纳替尼对人血管内皮细胞功能的影响[J].药物评价研究,2015,38(2):156-160.
[19] Bairey Merz C N,Pepine C J. Syndrome X and microvascular coronary dysfunction[J]. Circulation,2011,124:1477-1480.
[20] Camici P G, Crea F. Coronary microvascular dysfunction[J]. N Engl J Med,2007,356:830-840.
[21]郑乘龙.益气活血药对心梗大鼠冠脉微血管内皮损伤活性分子的调控机制研究[D].北京:北京中医药大学,2012.
[22]黄琨.益气活血中药对心梗大鼠冠脉微血管功能障碍及相关分子调控机制的研究[D].北京:北京中医药大学,2013.
[23]杜海波,麝香保心丸治疗微血管功能障碍的研究进展[J].世界最新医学信息文摘,2016,16(56):34-35.
[24] Lanza G A,Crea F. Primary coronary microvascular dysfunction:clinical presentation,pathophysiology,and management[J]. Circulation,2010,121(21):2317-2325.
[25]逯雯洁,王慧春,海平,等.高效液相色谱法同时测定二十五味珍珠丸中7种成分及其特征图谱[J].中国医院药学杂志,2016,36(21):1885-1890.
[26] Herrmann J, Kaski J C, Lerman A. Coronary microvascular dysfunction in the clinical setting:from mystery to reality[J]. Eur Heart J,2012,33(22):2771-2783.
[27]刘旭杰,秦烨,陈淑珍.吉西他滨对肺微血管内皮细胞的损伤及表没食子儿茶素没食子酸酯的保护作用[J].中国医药生物技术,2014,9(6):438-445.
[28]郭建友,霍海如,刘洪斌,等.桂皮醛对IL-1刺激下脑微血管内皮细胞COX-1、COX-2活性及释放PGE2的影响[J].中药药理与临床,2005,21(6):16-18.
[29] McGrath P,LI C Q,Zebrafish:a predictive model for assessing drug-induced toxicity[J]. Drug Discov Today,2008,13(9/10):394-401.
[30]高家荣,郭明飞,方朝晖,等.黄地安消胶囊对高糖高脂诱导的斑马鱼血管病变保护作用研究[J].中国中药杂志,2018,42(21):4317-4322.
[31]李晓稳,佟玲,李东翔,等.斑马鱼神经元损伤模型在养血清脑颗粒质量控制中的应用分析[J].中国实验方剂学杂志,2016,22(9):1-4.
[32]罗隽,梅雪,夏青,等.醋甘遂不同提取物对斑马鱼幼鱼的毒性[J].中国实验方剂学杂志,2018,24(4):160-166.