摘要
目的:观察人参皂苷Rg1对急性心肌梗死后血管新生及梗死区血管内皮生长因子和缺氧诱导因子1αmRNA表达的影响及其机制。方法:实验于2005-10/2006-01在中国医科大学附属第一医院循环内科实验室完成。实验分组:健康雄性Wistar大鼠104只,体质量180～220g,随机抽签法分为假手术组8只,对照组、Rg1低剂量治疗组和Rg1高剂量治疗组各32只。实验方法:建立Wistar大鼠急性心肌梗死模型,假手术组开胸不结扎冠状动脉,3d后处死取材;对照组、Rg1低剂量治疗组和Rg1高剂量治疗组分别于术后即刻及术后每天腹腔注射生理盐水1mL、人参皂苷Rg11mg/kg和5mg/kg,术后3,7,10,14d分别取材,每组8只。实验评估:测定血清心肌酶、心肌梗死面积、梗死区微血管密度,逆转录-聚合酶链反应检测梗死区心肌组织血管内皮生长因子和缺氧诱导因子1α的mRNA表达。结果:纳入大鼠104只,均进入结果分析。①人参皂苷Rg1对大鼠心肌酶及心肌梗死面积的影响:Rg1低剂量治疗组、Rg1高剂量治疗组心肌酶较对照组明显降低[(62.25±10.79),(57.64±9.36),(78.63±11.34)μg/L;P<0.05],心肌梗死面积亦明显降低[14d:(12.15±3.68)%,(10.10±3.12)%,(13.94±3.54)%;P<0.05]。②人参皂苷Rg1对大鼠心肌梗死区微血管密度的影响:各组梗死区血管生成数量随着时间的延长呈持续增加的趋势,与对照组比较,差异有显著性意义[Rg1低剂量治疗组14d:(17.29±3.21)个/视野;Rg1高剂量治疗组14d:(23.27±3.42)个/视野;对照组14d:(9.36±3.54)个/视野;P<0.01]。③大鼠心肌梗死区血管内皮生长因子、缺氧诱导因子1αmRNA的表达:心肌梗死后血管内皮生长因子、缺氧诱导因子1αmRNA表达随缺血时间的延长有增高趋势,Rg1低剂量治疗组与Rg1高剂量治疗组明显升高,14d时血管内皮生长因子的增长出现停止或下降[Rg1低剂量治疗组14d:(1.1637±0.1786);Rg1高剂量治疗组14d:(1.7230±0.3102)];而缺氧诱导因子1α继续升高[Rg1低剂量治疗组14d:(1.7263±0.3417);Rg1高剂量治疗组14d:(2.7725±0.3219)]。结论:严重缺血可刺激心肌组织产生大量的血管内皮生长因子、缺氧诱导因子1α,人参皂苷Rg1增加其表达进而刺激心肌梗死区的血管生成,减轻缺血对心肌的损伤。
AIM：To observe the influence of ginsenoside Rg1 on angiogenesis and the expressions of vascular endothelial growth factor （VEGF） and hypoxia inducible factor-lα （HIF-1α） in rats after acute myocardial infarction.
METHODS： The experiment was conducted in the laboratory of Department of Circulatory Medicine, First Affiliated Hospital, China Medical University from January 2005 to January 2006. 104 male healthy Wistar rats of 180-220 g were randomly divided into sham-operation group （n =8）, control group （n =32）, low ginsenoside Rg1 group （n =32） and high ginsenoside Rg1 group （n =32）. Rat models of acute myocardial infarction were established; the sham-operation group was not treated with coronary artery ligation, and the rats were executed after three days; the control group, low and high ginsenoside Rg1 groups ware intraperitoneally injected with 1 mL normal saline, 1 mg/kg and 5 mg/kg ginsenoside Rg1 respectively immediately and every after operation; then 8 rats of each group were sampled at 3, 7, 10, and 14 daya after operation. Myocardial enzyme, myocardial infarct area, and microvascular density ware determined, and VEGF and HIF-1α mRNA expressions were detected by RT-PCR.
RESULTS： 104 rats were involved in the result analysis. ①Influence of ginsenoside Rg1 on myocardial enzyme and myocardial infarct area： The myocardial enzyme of the low and high ginsenoside Rg1 groups was significantly reduced compared with the control group [（62.25±10.79）, （57.64±9.36）, （78.63±11.34） μg/L; P 〈 0.05], so was the myocardial infarct area 14 days： [（12.15±3.68）%, （10.10±3.12）%, （13.94±3.54）%; P 〈 0.05]. ②Influence of ginsenoside Rg1 on microvascular density： The amount of angiogenesis in the infarct region of each group was continuously elevated with time, which had significantly differences compared with the control group [low dose group at 14 days： （17.29±3.21） per field; high dose group at 14 days： （23.27±3.42） per field; control group at 14 days： （9.36±3.54） per field; P 〈 0.01]. ③ Expressions of VEGF and HIF-1α mRNA： These expressions after acute myocardial infarction were increased with ischemic time, especially the low and high ginsenoside Rg1 groups; at day 14, the increase of the expression of VEGF stopped or reduced [low dose group at 14 days： （1.163 7±0.178 6）; high dose group at 14 days： （1.723 0±0.310 2）], while the expression of HIF-1α continuously increased [low dose group at 14 days： （1.726 3±0.341 7）; high dose group at 14 days： （2.772 5±0.321 9）].
CONCLUSION： Acute ischemia strongly stimulates Ginsenoside Rg1 could promote their expressions to ischemia-induced myocardial damage. the production of VEGF and HIF-1α mRNA in myocardium. stimulate the angiogenesis in infarct region, and relieve the
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第14期2613-2616,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
作者简介
金岩．女．1972年生。辽宁省沈阳市人，回族，中国医科大学在读博士，主治医师，主要从事心肌梗死后血管新生等保护机制的研究。jinyan4158@vip．sina.com
通讯作者：刘闺男，硕士，教授，博士生导师，中国医科大学附属第一医院循环内科，辽宁省沈阳市110001
