【摘要】 目的评价血清基质金属蛋白酶9（MMP-9）、外周血白细胞（WBC）计数与2型糖尿病（DM）及其大血管病变的关系,并探讨罗格列酮（RSG）血管保护作用的机制。方法用酶联免疫吸附法（ELISA）测定30名健康对照者和80例2型DM患者（其中单纯DM者40例,合并大血管病变者40例）血清MMP-9水平,并同时测定外周血WBC计数和其他临床指标。32例2型DM患者用RSG（4 mg qd）干预治疗,于治疗4周（17例患者）和12周（所有患者）复查各指标,观察治疗前、中、后MMP-9、WBC以及各代谢指标的变化。结果与健康对照组相比,DM患者外周血MMP-9、WBC明显升高,合并大血管病变者[579（440-949）μg/L,（7．51±1．47）×10⁹/L]明显高于无合并症者[324（275-423）μg/L,（6．22±0．79）×10⁹/L]（P＜0．05或P＜0．01）。两指标呈高度正相关（r=0．874,P＜0．01）。MMP-9、收缩压（SBP）是2型DM大血管病变的独立危险因素,高密度脂蛋白胆固醇（HDL-C）是保护因素。RSG治疗12周后MMP-9、WBC水平分别由6．20±0．59（ln MMP-9）、（7．03±1．39）×10⁹/L降至6．01±0．50,（6．18±1．18）×10⁹/L,差异有统计学意义（均P＜0．01）,同时血糖、SBP、HOMA-IR等水平也明显下降,HDL-C升高。在治疗4周时,MMP-9、WBC水平即明显下降,但是各代谢指标的变化尚无统计学意义。MMP-9、WBC的下降幅度相关（r=0．762,P＜0．01）,且两者的降低均与HbA_1C的降低（P＜0．01）、HDL-C的升高呈正相关（P＜0．05）。结论血清MMP-9是2型DM大血管病变的独立危险因素；以WBC升高为表征的亚临床炎症与胰岛素抵抗、2型DM发病及其大血管病变的形成之间存在一定关系。RSG能明显降低血MMP-9、WBC水平,发挥抗炎、抗动脉粥样硬化作用,在抗血管病变上起有益作用。更多还原

【Abstract】 Objective To evaluate the relationship between serum matrix metalloproteinase-9（MMP-9）, white blood cell（WBC）count and type 2 diabetes mellitus with macroangiopathy and to investigate the mechanism of the protective effects of rusiglitazone（RSG）on blood vessel.Methods Serum MMP-9 was determined by ELISA in 30 normal controls and 80 type 2 diabetic patients（including 40 cases with macroangiopathy and 40 without maeroangiopathy）.WBC count and other clinical parameters were also determined.32 type 2 diabetic patients received RSG（4rag qd）for 12 weeks.All parameters were determined after 4 weeks（17 patients）and after 12 weeks（all patients）to observe the changes in MMP-9,WBC and other parameters.Results In the diabetic patients,serum MMP-9 and WBC were markedly higher as compared with normal controls;and MMP-9 and WBC in patients with macroangiopathy[579（440-949）μg/L,（7.51±1.47）×10⁹/L]were higher than those [324（275-423）μg/L,（6.22±0.79）×10⁹/L]in the cases without macroangiopathy（P<0.05 or P<0.01）. Serum MMP-9 was significantly correlated positively with WBC（r=0.874,P<0.01）.MMP-9,systolic blood pressure（SBP）were independent risk factors of macroangiopathy in type 2 DM,and the high density lipoprotein chelesterel（HDL-C）was a protective factor.RSG treatment for 12 weeks significantly reduced MMP-9 level[6.01±0.50 vs 6.20±0.59（InMMP）,P<0.01]and WBC count[（6.18±1.18）×10⁹/L vs（7.03±1.39）×10⁹/ L,P<0.01],meanwhile blood glucose,SBP,HOMA-IR were decreased,and HDL-C was increased.After 4 weeks of RSG treatment,WBC and MMP-9 levels were already decreased significantly（P<0.05 or P<0.01）, while the changes in metabolic parameters showed no statistical significance.The change of MMP-9 was positively correlated with the change of WBC（r=0.762,P<0.01）,and both changes were significantly correlated with the reduction of HbA_（?）c and increase of HDL-C.Conclusion MMP-9 is an independent risk factor of macroangiopathy in type 2 DM.Subclinical inflammation reflected by the increase of WBC is associated with insulin resistance and development of type 2 DM and macroangiopathy.RSG can significantly reduce the levels of MMP-9 and WBC in type 2 DM patients,indicating its potentially beneficial effects on the overall macrovascular complications.更多还原