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[摘要] 目的:观察胰岛素增敏剂治疗对2型糖尿病患者(T2DM) 金属基质蛋白酶-9 (MMP-9)表达改变的影响。方法:188例T2DM患者随机分为对照组和干预组,均给予正规糖尿病治疗,干预组加用罗格列酮8 mg,qd。在治疗前和治疗后2个月时分别采用ELISA检测血清MMP-9的表达量。结果:治疗前有大血管病变组患者的MMP-9值明显高于无大血管病变组者(t=3.325,P=0.001)。治疗后对照组的MMP-9值较治疗前未有有统计意义的下降(t=0.800,P=0.425);而干预组的MMP-9值较治疗前明显下降(t=4.405,P=0.000);治疗后干预组的MMP-9值较对照组明显下降(t=3.431,P=0.001)。分层分析显示罗格列酮干预对有大血管病、代谢综合征的T2DM患者,治疗后MMP-9改变更为明显。结论:胰岛素增敏剂罗格列酮能够减慢2型糖尿病患者大血管动脉粥样硬化的进程,这种作用在已经存在大血管病变和代谢综合征的2型糖尿病患者表现更为明显。
[关键词] 2型糖尿病;大血管病变;代谢综合征;胰岛素增敏剂;金属基质蛋白酶-9(MMP-9)
[中图分类号] R781.6+4 [文献标识码]A [文章编号]1674-4721(2010)04(c)-005-03
The impact of matrix metalloproteinase 9 in type 2 diabetic patients with macroangiopathy after application of Insulin sensitizers
ZHOU Guilian,ZHANG Chi,LI Huazhu
(The People"s Hospital of Hunan Province,Changsha410005, China)
[Abstract] Objective: To observe the impact of matrix metalloproteinase -9 (MMP-9) expression in application of insulin sensitizer in type 2 diabetes (T2DM). Methods: 188 patients with T2DM were randomly divided into control group and intervention group. All of them were given the formal treatment of diabetes, the intervention group added with rosiglitazone 8 mg,qd. Before the treatment and two months after treatment, serum MMP-9 expression were detected by ELISA. Results: Before treatment, MMP-9 in patients with macroangiopathy was significantly higher than those without macroangiopathy (t=3.325,P=0.001). After treatment, the MMP-9 did not have statistically significant decrease (t=0.800,P=0.425) in the control group; while in the intervention group, the MMP-9 decreased significantly (t=4.405,P=0.000 ); after treatment, the MMP-9 in intervention group decreased significantly than that of the control group (t=3.431,P=0.001). Stratification analysis showed that MMP-9 change more apparent after rosiglitazone intervention in patients with macroangiopathy, the same as metabolic syndrome T2DM patients. Conclusion: Rosiglitazone can slow down macrovascular atherosclerosis process in patients with type 2 diabetes, this effect become more evident in T2DM with macrovascular diseases or metabolic syndrome.
[Key words] 2 diabetes mellitus;Macroangiopathy;Metabolic syndrome;Insulin-sensitizing agent;MMP-9
糖尿病大血管病变是指中等或较大的动脉发生了粥样硬化(atherosclerosis,AS),主要累及主动脉、冠状动脉、脑动脉、肾动脉和周围血管等大血管,临床常见疾病是冠心病、脑卒中和下肢动脉硬化、坏疽等。糖尿病大血管并发症是糖尿病患者致死、致残的最主要原因之一,尤其是并发各种形式的心血管疾病时,其死亡率是非糖尿患者群的2~8倍,75%～80%的糖尿病患者死于大血管病变[1]。在糖尿病大血管病变中胰岛素抵抗不仅是AS发生的始动环节,并且加速了AS的发展[2]。大量研究[3]证实金属基质蛋白酶(Matrix Metalloproteinase, MMP)在降解细胞外基质(ECM),促进AS斑块的形成和破裂,发挥着重要作用。本研究观察胰岛素增敏剂治疗后2型糖尿病患者(T2DM)MMP-9表达的改变,为胰岛素增敏剂预防和治疗T2DM的AS作用提供客观证据。
1 资料与方法
1.1 一般资料
以2009年1～12月入本院治疗的T2DM患者为研究对象。纳入标准:①符合WHO1999年T2DM的诊断及分型标准;②既往未服用过胰岛素增敏剂类药物;③对本研究知情同意;④依从性好,随访资料完整者。排除标准:①严重肝肾功能损害;②严重心脏疾病;③肿瘤;④各种感染。共入选患者188例,其中,男101例,女87例;年龄41～75岁,平均(61.2±10.1)岁。根据大血管病变的诊断依据:①有典型心绞痛或心肌梗死病史及心电图表现者,或经冠状动脉造影明确诊断者;②有间歇性跛行或经超声证实有外周血管AS斑块者;③病史中出现偏瘫或其他脑局灶症状,并以脑CT扫描或磁共振成像显示有缺血或出血改变者,188例T2DM患者中存在大血管病变的共31例。代谢综合征的诊断参照ATPⅢ标准,188例T2DM患者中存在代谢综合征的共59例。
1.2 分组和治疗方式
将188例患者随机分为两组,每组各94例。两组患者在年龄、性别、种族、疾病的严重程度和并发症发生比例等因素上具有可比性。对照组患者均给予正规的糖尿病治疗,包括饮食控制、运动疗法、口服二甲双胍、格列本脲或采用胰岛素治疗;试验组患者在此基础上加用胰岛素增敏剂罗格列酮(文迪雅,葛兰素史克中国投资有限公司生产)8 mg,每日1次,口服。治疗期间均保证患者的饮食、运动及其他治疗药物保持相对稳定,血糖控制标准为2002年亚太地区T2DM政策组制定的血糖控制理想标准,即空腹血糖(FPG)4.4～6.1 mmol/L,餐后2 h血糖(2hPG)≥4.4～8.0 mmol/L。血压控制于130～140/80～90 mmHg。若有低血糖发生可适当减少降糖药用量。
1.3 血清MMP-9的检测
所有患者在治疗前和治疗后2个月时分别2次检测MMP-9。在空腹12 h后次晨抽取静脉血样本,采用酶联免疫吸附法(ELISA)进行监测,试剂盒由美国R&D System提供,批内变异系数(CV) [3]Lemaitre V,O"Byrne TK,Borczuk AC,et al.ApoE knockout mice expressing human matrix metalloproteinase-1 in macrophages have less advanced atherosclerosis[J].Ournal Of Clinical Investigation,2001,107(10):1227-1234.
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(收稿日期:2010-03-10)
