MMP-1, MMP-9 and TIMP-1 can be used as an important indicator of the dynamic balance of myocardial matrix remodeling
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摘要:
目的从基质金属蛋白酶（matrix metalloproteinase, MMPs）和基质金属蛋白酶组织抑制剂（tissue inhibitor of metalloproteinase, TIMps）的动态平衡着手探寻其对心肌基质的组织修复和再生作用，为心肌损伤后基质重构造成的心肌肥大、增厚等引起的心力衰竭提供的有效的生物检测方法及治疗。 方法利用广州市红十字会医院（暨南大学第四附属医院）的心脏病患者作为研究对象，按照随机区组分组的方法根据进行的心脏手术不同，将研究对象分为3个组，第1组为先天性心脏病组（CHD组）；第2组为风湿性心脏病组（PHD组）；第3组为冠心病组（COR组），由于其房室大小，心功能正常，设其为对照组。Elisa法对患者术前血液中的mmps和timps进行定量测定，寻求它们之间的动态平衡关系；术中切取心肌组织，用免疫组化方法测定心肌基质的胶原形态和分布；rt-PCR技术对心肌组织中mmps和timps的mRNA进行检测，查看其mRNA表达情况。 结果CHD组、PHD组术前血液中的MMP-3、MMP-9、TIMP-1含量均较COR组高，MMP-9增多更为显著，差异有统计学意义（P < 0.05），而CHD组和PHD组差异不显著，无统计学意义；免疫组化结果显示，CHD组、PHD组中MMP-3、MMP-9、TIMP-1均较COR组分布广泛，PCR结果显示CHD组、PHD组患者MMP-1、MMP-9、TIMP-1的mRNA表达较COR组升高，差异有统计学意义（P < 0.05），同样CHD组和PHD组差异不显著，无统计学意义。 结论MMP-1、MMP-9和TIMP-1的动态平衡可作为心肌基质重构的重要标志，调节MMPs和TIMPs的活性有望成为心脏病治疗的新方向。 -
关键词:
- 基质金属蛋白酶 /
- 基质金属蛋白酶组织抑制剂 /
- 基质重构 /
- 心肌损伤
Abstract:ObjectiveFrom the homeostasis of MMPs and TIMPs to explore its role in tissue repair and regeneration of cardiac matrix, thus it can provide an effective biological detection methods and treatment of heart failure that caused by matrix remodeling after myocardial injury, myocardial hypertrophy and thickening. MethodsUse Guangzhou Red Cross Hospital (Fourth Affiliated Hospital of Jinan University) for heart patients as research subjects, according to the method of random block cardiac surgery grouped according to different subjects were divided into three groups, the first group of congenital heart disease group (CHD group); second group of rheumatic heart disease group (PHD group); third group of CHD (COR group), because of its atrioventricular size, normal heart function, set it as a control group. Elisa method for preoperative blood mmps and quantitative determination timps seeking dynamic balance between them; intraoperative myocardial tissue cut, shape and distribution of the determination of myocardial collagen matrix by immunohistochemistry; rt-PCR technique myocardial tissue mRNA mmps and timps for testing, to see its mRNA expression. ResultsCHD group, PHD group before surgery blood MMP-3, MMP-9, TIMP-1 levels were higher than COR group, MMP-9 increased even more significant, the difference was statistically significant (P < 0.05), while the CHD group PHD group and no significant difference was not statistically significant; immunohistochemistry showed, CHD group, PHD group, MMP-3, MMP-9, TIMP-1 is widely distributed than COR group, PCR results showed that CHD group, PHD group patients with MMP-1, MMP-9, TIMP-1 mRNA expression increased compared with COR group, the difference was statistically significant (P < 0.05), the same group and PHD CHD group had no significant difference was not statistically significant. ConclusionsMMP-1, MMP-9 and TIMP-1 can be used as an important indicator of the dynamic balance of myocardial matrix remodeling, regulate the activity of MMPs and TIMPs is expected to become the new direction of heart disease treatment. -
Key words:
- MMPs /
- TIMPs /
- matrix remodeling /
- myocardial injury
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图 1 MMP-3、MMP-9、TIMP-1在三组患者血中的含量
CHD组与COR组比较, #P < 0.05; PHD组与COR组比较, *P < 0.05.
Figure 1. The levels of MMP-3, MMP-9, TIMP-1 in three groups of patients with blood.
图 2 MMP-3、MMP-9、TIMP-1的免疫组化形态分布
A（CHD组）、B (PHD组）、C（COR)组，1（MMP-3)、2(MMP-9)、3(TIMP-1).
Figure 2. The immunohistochemical species distribution of MMP-1、MMP-9、TIMP-1.
表 1 三组患者的临床资料对比
Table 1. The clinical data of three groups patients
Group n LAD LEVD RAD LVEF IVS LVPW CHD 30 29.9±2.48 40.8±2.6 41.7±2.5 0.61±0.02 8.1±0.5 8.1±0.5 RHD 28 42.1±2.88 49.4±3.0 28.0±2.9 0.64±0.02 11.0±1.1 8.6±0.5 COR 25 28.9±2.69 40.6±2.5 29.2±2.1 0.72±0.04 8.4±0.7 8.4±0.7 p* 0.235 0.960 0.000 0.000 0.312 0.119 P# 0.000 0.000 0.829 0.000 0.000 0.433 LAD (左房末径）、LEVD（左室末径）、RAD（左房末径）、IVS（室间隔厚度）、LVEF（射血分数）、LVPW（左室后壁）、*（CHD与COR比较）、#（RHD与COR比较）. 
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表 2 三组患者的mRNA表达情况
Table 2. The mRNA expression of three group
Group n MMP-3 MMP-9 TIMP-1 CHD 30 0.45±0.08 0.55±0.06 3.98±0.25 RHD 28 0.45±0.09 0.56±0.09 4.08±0.40 COR 25 0.39±0.07 0.49±0.06 3.72±0.53 F 3.95 7.73 5.52 P# 0.047 0.005 0.046 P* 0.020 0.001 0.003 #（CHD组与COR组比较）、*（PHD组与COR组比较）.
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