il-6、il-10和mmp-1与冠心病的关系及氟伐他汀对其水平的影响

1、IL-6、IL-10 和 MMP-1 与冠心病的关系及氟伐他汀对其水平的影响硕士研究生 邓孟球导师文红艳教授中 文 摘 要目的通过检测冠状动脉造影冠脉正常者和冠心病患者（包括急性心肌梗死、不稳定型心绞痛和稳定型心绞痛）血清白细胞介素 -6（IL-6）、白细胞介素-10（IL-10）、基质金属蛋白酶-1（MMP-1）浓度及冠心病患者经氟伐他汀不同剂量治疗后上述因子的浓度，探讨：血清 IL-6、IL-10 和 MMP-1 与冠心病的关系；不同剂量氟伐他汀治疗冠心病,血清 IL-6、IL-10 和 MMP-1 水平的变化及可能机制。方法 选择经冠状动脉造影证实的住院冠心病患者 51 例：急性心肌梗塞

2、（AMI）13 例，不稳定型心绞痛（UAP）18 例，稳定型心绞痛(SAP)20 例；冠脉造影正常的对照者 20 例。入选当天抽取空腹静脉血 5ml 后，冠心病患者随机分为两组，分别给予氟伐他汀 40mg/天和 80mg/天，睡前服用，一月后再次采空腹静脉血 5ml。采用 ELISA 测定 IL-6、IL-10 和 MMP-1 浓度。SPSS13.0 统计软件对检测结果组间及治疗前后进行比较，计量资料以 x S 表示，计量资料统计前进行正态性检验和方差齐性检验，多组间比较采用单因素方差分析，治疗前后比较采用配对 t检验，两组间的比较采用两样本 t 检验，两变量的相关采用 Pearson 直线相

3、关分析。双侧 P0.05 为差异有统计学意义，双侧 P0.01 为差异有显著性。结果 治疗前：血清 IL-6、MMP-1 浓度在 AMI 和 UAP 组中显著升高，与 SAP组和对照组比较有显著性差异（P0.01）；血清 IL-6、MMP-1 浓度在 SAP 组和1对照组间比较无显著性差异；血清 IL-6 浓度在 AMI 组和 UAP 组间比较有显著性差异（P0.01）；血清 MMP-1 浓度在 AMI 组与 UAP 组间比较则无显著性差异；血清 IL-10 浓度在 AMI、UAP、SAP 和对照组间无显著性差异；血清 IL-6水平与血清 MMP-1 水平呈显著正相关（r0.847P0.01）

4、；血清 IL-6、IL-10、MMP-1 水平与冠状动脉粥样硬化病变支数无相关性。经氟伐他汀治疗后：40mg组和 80mg 组血清 IL-6、MMP-1 浓度均有明显下降，但 80mg 组下降更甚，前后比较均有显著性差异（P0.01），两组间比较亦有显著性差异（P0.01）；血清IL-10 浓度在治疗前后均无明显变化，组内治疗前后比较和组间比较均无显著性差异。结论 IL-6、MMP-1 在 ACS 患者中血清水平明显升高，可能与炎症反应、斑块不稳定相关，从而促进了冠心病患者发展为临床上的 ACS；IL-10 在冠心病患者血清水平中无明显变化；IL-6、MMP-1 和 IL-10 与冠脉病变支数

5、无关；氟伐他汀可能通过抑制 IL-6、MMP-1 的水平而发挥抗炎作用，其效用与药物浓度相关。关键词 冠心病；急性冠脉综合征；白细胞介互素-6；白细胞介素-10；基质金属蛋白酶-1；氟伐他汀。2A study on relationship between serumConcentrations of IL-6, IL-10 , MMP-1 andCoronary Heart Diseases and their varianceafter treatment by FluvastatinABSTRACTObjective by detecting the serum concentratio

6、ns of interleukin-6(IL-6), inter-leukin-10(IL-10) and matrix metalloproteinases-1(MMP-1) in patients with coronaryartery diseases before and after treatment by different dose Fluvastatin, to research: the the relationship between serum comcetrations of IL-6,IL-10,MMP-1 andCoronary Heart Diseases; th

7、e changes of the serum levels of IL-6,IL-10 andMMP-1 after Fluvastatin treatment and the mechanisms of Fluvastatin in curingpatients with coronaty heart diseases.Methods51 consecutive patients with CHD were diagnosed by coronaryangiography in the hospitalized patients in the first affiliated hospita

8、l of Nanhuauniversity. Each one had greater than 50% stenoses of one coronary artery. Serumconcentrations of IL-6, IL-10 and MMP-1 were measured in 13 patients with acutemyocardial infarction(AMI), 18 patients with unstable angina pectoris(UAP), 20Patients with stable angina pectoris(SAP) and 20 con

9、trols, who were no-affectedcoronary artery diagnosed by coronary angiography,by enzyme-linkedimmunosorbent assay(ELISA). Then,51 patients with CHD were randomly dividedinto 2 groups: 40mg group and 80mg group treated by FLuvastatin. After 30 daystherapy, the serum level of IL-6, IL-10 and MMP-1 were

10、 compared among all groups.Statistical analysis were performed using SPSS 13.0 for PC. Values were expressed asmeanstandard deviation ( x S) for measurement data and number or3percentage(%)for enumeration count data. For measurement data, comparisons amongdifferent groups were made by one-way analys

11、is of variance(ANOVA)and two groupswere made by a two-tailed Student,s t-test or matched t-test; for enumeration countdata, comparions made by Pearson chi-square test and Fishers exact test; Forbivariate normal distribution data,correlation was made by Person liner correlation.Difference were regard

12、ed as statistically significant when P values was 0 .0 5 )21IL-6（ p g /m l ）IL-1 0（ p g /m l ）30.00浓度25.0020.0015.0010.005.000.00AMIUAPS APN图4 AMI、UAP 、S AP 和对照组血清MMP -1 浓度（ng/m l）(P 0.01 com pa re d with control group;P 0.01 com pa re d with S AP group.)4 治疗前冠脉病变支数各组 IL-6、IL-10、MMP-1 水平（见表 4）冠脉病变支数

13、各组：IL-6、IL-10、MMP-1 水平无明显差异（P0.05）。表 4冠脉病变支数各组血清 IL-6、IL-10、MMP-1 水平Table 4fixedThe serum level of IL-6，IL-10 and MMP-1 in different significantCoronary Arteria disease groups(IL-6, IL-10 unit： pg/ml;MMP-1unit：ng/mlx s)Groups1sf-CAD g2sf-CAD g3sf-CAD gn162015IL-69.344.319.103.8610.624.27IL-1032.565.

14、2631.594.4732.084.56MMP-117.617.1018.837.5819.648.05sf-CAD: significant fixed coronary artery disease; P0.05.5 治疗前血清 IL-6、IL-10、MMP-1 水平间的相关关系及与冠脉病22MMP -1（ n g /m l ）变支数的相关关系血清 IL-6 水平与 IL-10 水平无显著相关性（r0.145P0.05），而与血清 MMP-1 水平呈显著正相关（见图 5 r0.847P0.01）；血清 IL-10 水平与MMP-1 水平亦无显著相关性（r0.066P0.05）。IL-6、I

15、L-10、MMP-1 与冠脉病变支数均无显著相关性（r0.1170.107P0.05）。35.0030.00浓度（25.0020.00）15.0010.005.00P0.05； r0.029P0.05； r2.004.006.008.0010.0012.0014.0016.00IL-6 浓度（pg/ml）图 5IL-6 与 MMP-1 直线回归方程图6 冠心病患者氟伐他汀 40mg 治疗组与 80mg 治疗组血清 IL-6、IL-10、MMP-1 水平（见表 5、图 6、图 7、图 8）治疗前两组间 IL-6、IL-10 和 MMP-1 浓度无显著性差异（P0.05）；经氟伐他汀治疗后两组血清 IL-6、MMP-1 水平均有明显下降，与治疗前比较有统计学意义（P0.01）,两组间比较有显著性意义（P0.01）；每组 IL-6、MMP-1治疗前后浓度差值相比，差异有显著性（P0.01）；治疗前后 IL-10 的水平无明23MMP-1ng/ml显变化，治疗前后比较和两组间