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[1]郑瑞玲,陈萌,娄利霞,等.活血益气方及其拆方对大鼠心肌梗死边缘区Spred1及血管新生的影响[J].环球中医药,2016,9(12):1437-1442.[doi:10.3969/j.issn.1674-1749.2016.12.001]
　ZHENG Rui-ling,CHEN Meng,LOU Li-xia,et al.Effects of Huoxue Yiqi prescription and its disassemble prescriptions on Spred1 and angiogenesis in rats with acute myocardial infarction[J].,2016,9(12):1437-1442.[doi:10.3969/j.issn.1674-1749.2016.12.001]
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活血益气方及其拆方对大鼠心肌梗死边缘区Spred1及血管新生的影响()
     
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《环球中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:
第9卷
期数:
2016年12期
页码:
1437-1442
栏目:
论著
出版日期:
2016-12-06

文章信息/Info

Title:
Effects of Huoxue Yiqi prescription and its disassemble prescriptions on Spred1 and angiogenesis in rats with acute myocardial infarction
作者:
郑瑞玲; 陈萌; 娄利霞; 吴爱明; 赵一舟; 赵久丽; 成文堃; 吕晞滢; 张冬梅
100700 北京中医药大学东直门医院中医内科学教育部和北京市重点实验室[娄利霞、吴爱明、赵一舟、赵久丽、成文堃(硕士研究生)、吕晞滢、张冬梅]; 北京中医药大学基础医学院(陈萌); 郑州市中牟县中医院内一科(郑瑞玲)
Author(s):
ZHENG Rui-ling;  CHEN Meng;  LOU Li-xia;  et al.
Dongzhimen Hospital Attached to Beijing University of Chinese Medicine, Beijing 100700, China
关键词:
活血益气方;  Spred1;  心肌梗死;  血管新生
Keywords:
Huoxue Yiqi prescription;  Spred1;  Myocardial infarction;  Angiogenesis
分类号:
R285.5
DOI:
10.3969/j.issn.1674-1749.2016.12.001
文献标志码:
A
摘要:
目的 观察活血益气方及其拆方对心肌梗死后大鼠梗死边缘区心肌组织血管新生负性调控因子Spred1及血管新生的影响,探讨活血益气方促血管新生的可能作用机制及配伍规律。方法 健康雄性SD大鼠30只,随机分为假手术组6只与手术组24只,手术组行左冠状动脉前降支结扎术制备急性心肌梗死模型,随机分为模型组、活血益气方组、益气方组、活血方组。假手术组只穿线不结扎。连续给予相应药物4周后,处死大鼠,取梗死边缘区心肌组织进行指标检测。采用免疫组织化学法观察微血管密度(microvasculardensity,MVD)、微血管平均直径(mean microvascular diameter,MMVD); 采用实时荧光定量PCR法检测Spred1 mRNA的表达; 采用Western Blot法检测Spred1蛋白的表达。结果(1)模型组MVD高于假手术组,MMVD小于假手术组(P＜0.01); 活血益气方组、益气方组、活血方组MVD高于模型组(P＜0.01或P＜0.05),其中以活血益气方组最为明显,MMVD大于模型组,仅活血益气方组与之比较具有统计学差异(P＜0.01); 益气方组、活血方组MMVD小于活血益气方组,分别与之比较,均具有统计学差异(P＜0.01)。(2)模型组梗死边缘区心肌组织Spred1 mRNA表达高于假手术组(P＜0.05); 活血益气方组、益气方组、活血方组Spred1 mRNA表达高于模型组,差异具有统计学意义(P＜0.01或P＜0.05); 益气方组、活血方组Spred1 mRNA表达均高于活血益气方组,仅活血方组与之比较具有统计学差异(P＜0.01)。(3)模型组梗死边缘区心肌组织Spred1表达高于假手术组,两者比较未见统计学差异(P＞0.05); 活血益气方组、益气方组、活血方组Spred1表达均低于模型组,比较差异具有统计学意义(P＜0.05); 益气方组Spred1表达低于活血益气方组,活血方组Spred1表达高于活血益气方组,分别与之比较,均未见统计学差异(P＞0.05)。结论 活血益气方及其拆方具有不同程度促进心肌梗死模型大鼠梗死边缘区血管新生的作用,以活血益气方作用最为显著,益气方、活血方在其中起协同作用,其作用机制可能与下调Spred1、上调其mRNA的表达有关。在Spred1 mRNA上调的情况下,Spred1表达降低,提示Spred1 mRNA可能存在转录后调节因子,其具体作用机制尚需进一步研究。
Abstract:
Objective To observe the impact of Huoxue Yiqi prescription on the negative regulation factor Spred1 and angiogenesis of myocardial tissue in the marginal zone of myocardial infarction rats, and to explore the mechanism and compatibility regularity of the compound decoction of Huoxue Yiqi prescription promoting therapeutic neovascularization. Methods Model rats of acute myocardial infarction(AMI)were established by ligation of left anterior descending coronary artery, and randomly divided into 4 groups. Therapeutic groups were treated with Huoxue Yiqi prescription(HXYQ), Yiqi prescription(YQ), Huoxue prescription(HX)and model group. Rats of sham group were treated with saline and operated without ligation. Animals were sacrificed and the myocardial infarction border areas were taken as indicators after 4 weeks of treatment. Microvascular density(MVD)and the mean microvessel diameter(MMVD)were assessed by immunohistochemistry. The expression of Spred1 mRNA and VEGF mRNA was detected by quantitative real-time PCR(qRT-PCR), and Western Blot was used to observe the expression of Spred1. Results(1)The MVD in model group was higher than that in sham group(P＜0.01). Compared with model group, HXYQ, HX and YQ group can improve MVD(P＜0.01 or P＜0.05), and the effect of HXYQ is the most significant. The MMVD in model group was higher than sham group(P＜0.01). Compared with model group, HXYQ,HX and YQ group could improve MMVD, but only HXYQ group had significant difference(P＜0.01). The MMVD in HXYQ group was higher than that in the other two therapeutic groups(P＜0.01).(2)The mRNA level of Spred1 in model group was higher than that in sham group(P＜0.05). Compared with model group, HXYQ, HX and YQ group could significantly improve the mRNA level of Spred1(P＜0.05). The mRNA level of Spred1 in HXYQ group was lower than that in HX group or YQ group. However it was only significantly lower than in HX group(P＜0.01).(3)The expression of Spred1 in model group was higher than sham group, but there was no significant difference(P＞0.05). Compared with model group, HXYQ, HX and YQ group could significantly reduce the expression of Spred1(P＜0.05). The expression of Spred1 in HXYQ group was higher than that in YQ group and lower than in HX group, but there was no significant difference(P＞0.05). Conclusion To varying degrees, HXYQ and its decomposed recipes can promote angiogenesis in myocardial infarction border areas in rats after AMI. The effect of HXYQ is the most significant. It's two decomposed recipes work synergistically. The mechanisms may be related with their effects on down-regulating Spred1 and up-regulating the mRNA level of Spred1. In addition, we found that the mRNA level of Spred1 increased while the expression of Spred1 decreased. It is suggesting that Spred1 mRNA may be regulated at the post-transcriptional level by other factor, therefore further researches regarding the specific mechanism may be needed.

参考文献/References:

[1] 乔树宾.冠心病诊疗进展[M].北京:人民卫生出版社,2013:53-56.
[2] 史载祥,黄春林,史大卓.现代中医心血管病学[M].北京:人民卫生出版社.2006:1-2.
[3] Giulio G, Stefanini M.D, David R, et al. Drug-eluting coronary-artery stents [J]. New England Journal of Medicine, 2013, 368(3): 254-265.
[4] Sellke FW, Simons M. Angiogenesis in cardiovascular disease: Current status and therapeutic potential [J].Drugs, 1999, 58(3):391-396.
[5] 李敏,王硕仁,赵明镜,等. 活血、益气方药对心梗后心衰大鼠血流动力学影响的实验研究[J]. 中国中医基础医学杂志,2001,7(6):22-24.
[6] 王振涛,王硕仁,赵明镜,等. 活血和益气方药对心肌梗死后左心衰大鼠左心室重构影响的比较研究[J]. 中国中西医结合杂志,2002,22(5): 376-378.
[7] 张冬梅,吴爱明,娄利霞,等. 活血益气方对心梗后大鼠缺血心肌血管新生及VEGF表达的影响[J]. 辽宁中医杂志,2010,37(8): 1602-1604.
[8] Wakioka T,Sasaki A,Kato R,et al.Spred is a Sprouty-related suppressor of Ras signalling[J].Nature,2001,412(6847):647-651.
[9] Chong H, Vikis HG, Guan KL. Mechanisms of regulating theRaf kinase family [J]. Cellular signalling, 2003, 15(5): 463-469.
[10] Nicoli S, Standley C, Walker P, et al. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis[J]. Nature, 2010, 464(7292): 1196-1200.
[11] 刘振,刘玲玲,杨廷桐.两种大鼠心肌梗死模型的比较研究[J].动物医学进展,2010,31(4):19-25.
[12] Weidner N,Semple JP,Welch WR,et al. Tumor angiogenesis and metastasis——correlation in invasive breast carcinoma[J].The New England journal of medicine,1991,324(1):1-8.
[13] Ware JA,Simons M. Angiogenesis in ischemic heart disease [J]. Nature Med,1997,3(2): 158-164.
[14] Isner JM,Rosenfield K,Losordo DW,et al. Percutaneous intravascular US as adjunct to catheter-based interventions: preliminary experience in patients with peripheral vascular disease [J]. Radiology,1990,175(1): 61-70.
[15] Majchrzak K,Kaspera W,Szyma J,et al. Markers of angiogenesis(CD31, CD34, rCBV)and their prognostic value in low-grade gliomas [J]. Neurologiai Neurochirurgia Polska,2013,47(4): 325-331.
[16] Sharma B,Singh N,Gupta N,et al. Diagnostic modalities of precancerous and cancerous cervical lesions with special emphasis on CD31 angiogenesis factor as a marker [J]. Pathology research international,2013: 243168.
[17] Hamzah J,Jugold M,Kiessling F,et al. Vascular normalization in Rgs5-deficientTumors promote immune destruction [J]. Nature,2008,453(7193): 410-414.
[18] De La Cruz JP,Gonzalez-Correa JA,Guerrero A,et al. Pharmacological approach to Diabetic retinopathy. [J]. Diabetes Metab Res Rev,2004,20(2): 91-113.
[19] Patrick S Ward,Craig B Thompson. Metabolic Reprogramming: A Cancer Hallmark Even War burg Did Not Anticipate[J].Cancer cell,2012,20(3):297-308.
[20] Hlatky L,Hahnfeldt P,Folkman J. Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us[J]. Journal of the National Cancer Institute,2002,94(12): 883-893.
[21] Banopadhyay R,Ort e C, Lawrenson JG, et al. Contractile proteins in pericytes at the blood-brain and blood-retinal barriers [J]. J Neurocytol, 2001, 30(1): 35-44.
[22] Nakano M, Atobe Y, Goris RC, et al. Ultrastructure of the capillary pericytes and the Expression of smooth muscle alpha-actin and desmin in the snake infrared sensory organs[J].The Anatomical Record, 2000, 260(3): 299-307.
[23] 王医术,李玉林,王心蕊,等.用α-SMA结合部位标记新生血管周细胞[J].吉林大学学报,2003,29(5):594-598.
[24] 于德新,张宗利,马祥兴,等. 血管生成及其成熟度在肝细胞癌边缘与中心的差异研究[J]. 中国现代普通外科进展,2009,12(2):113-117.
[25] 滕建英,郭瑞,谢菁,等.血管内皮生长因子DNA质粒对真皮支架修复猪Ⅲ度烧伤创面中血管化的影响[J].中华医学杂志,2011,91(36):2568-2872.
[26] 张静,王华,王立生. Spred的结构及生物学特性[J]. 军事医学科学院院刊,2009,33(1):74-77.
[27] Jiang ZY,He Z,King BL,et al. Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis[J].The Journal of biological chemistry,2003,278(34):31964-31971.
[28] Wang S,Aurora AB,Johnson BA,et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis[J].Developmental Cell,2008,15(2): 261-271.
[29] Jakob P,Doerries C,Briand S,et al. Loss of angiomiR-126 and 130a in angiogenic early outgrowth cells from patients with chronic heart failure: role for impaired in vivo neovascularization and cardiac repair capacity[J]. Circulation,2012,126(25):2962-2975.

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备注/Memo

备注/Memo:
基金项目: 国家自然科学基金面上项目(81273694)
作者简介: 郑瑞玲(1986- ),女,硕士,住院医师。研究方向:中西医结合心血管疾病的应用基础研究。E-mail:752682356@qq.com
通讯作者:张冬梅(1975- ),女,博士,副研究员。研究方向:中西医结合心血管疾病的应用基础研究。E-mail:chaweto@126.com
更新日期/Last Update: 2016-12-06