摘要
目的探讨基质金属蛋白酶9表达和活化与2型糖尿病大鼠大血管病变的关系以及罗格列酮抗动脉粥样硬化的分子机制。方法应用高脂饲料加小剂量链脲佐菌素建立2型糖尿病大鼠模型,用含明胶十二烷基硫酸钠—聚丙烯酰胺凝胶电泳方法检测基质金属蛋白酶9活性,用逆转录聚合酶链反应检测基质金属蛋白酶9 mRNA的表达,并观察罗格列酮治疗48、和12周基质金属蛋白酶9的表达及活性的变化。结果糖尿病组大鼠主动脉基质金属蛋白酶9的活性是正常大鼠的1.37倍,且随着糖尿病病程的延长而增强,分别是正常组大鼠的1.69、2.25和2.92倍,基质金属蛋白酶9 mRNA的表达呈增高趋势,分别是正常组的1.15、1.30、1.45和1.99倍;罗格列酮治疗后基质金属蛋白酶9的活性分别比模型组降低11.56%、37.73%和48.60%,基质金属蛋白酶9 mRNA表达量分别比模型组降低26.80%、27.16%和46.46%。结论在2型糖尿病大血管病变形成过程中,伴有基质金属蛋白酶9表达和活性的变化,罗格列酮防治糖尿病大血管病变的机制与抑制基质金属蛋白酶9基因表达和活性有关。
Aim To investigate the association between expression and activity of matrix metalloproteinase-9 （MMP-9） and type 2 diabetic macroangiopathy and explain the mechanism of anti-atherosclerosis effect of Rosiglitazone. Methods Type 2 diabetic rat model was established by high-fat diet and a low dose of STZ. The activity of MMP-9 in arterial wall was observed by SDS-PAGE zymography. The MMP-9 mRNA expression in arterial wall was observed by RT-PCR. Meanwhile the changes of MMP-9 expression and activity were observed after Rosiglitazone treatment for 4, 8 and 12 weeks. Results The activity of MMP-9 in model rats was 1.27 times as high as that of control rats, with the prolongaton of diabetes duration and the development of macroangiopathy, its activity increased progressively and was 1.69, 2.25 and 2.92 times of control rats, respec- tively, at week 4, 8 and 12 after DM, MMP-9 mRNA in n^xlel rats was 1.15, 1.30, 1.45 and 1.99 times higher than that of control rats at week 0, 4, 8 and 12 after DM. MMP-9 activity was dropped by 11.56%, 37.73 % and 48.60 % in Rosiglitazone group after treatment for 4, 8 and 12 weeks, MMP-9 mRNA was dropped by 26.80%, 27.16% and 46.46% in Rosiglitazone group after treatment for 4, 8 and 12 weeks. Conclusions The changes of MMP-9 expression and activity occured during the development of type 2 diabetic macroartgiopathy. The mechanisms of anti-atherosclerosis effect of Rosiglitazone might be related to inhibiting MMP-9 expression and activity.
出处
《中国动脉硬化杂志》
CAS
CSCD
2006年第2期93-96,共4页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金(90208014)资助
作者简介
刘宽芝，医学博士，主任医师，教授，硕士研究生导师，主要从事糖尿病慢性并发症的研究，E-mail为liukuanzhi@Medmail.com,
吕海莉，硕士，主治医师，现工作单位为邯郸钢铁公司职工医院。
王伟超，硕士研究生。
