Hu Chun-Yang, Ding Wen-Hui, Han Xiao-Ning, Chu Song-Yun, Hao Yan-Jie, Bu Ding-Fang
Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Mar;36(3):243-8.
We investigated the in vivo effects of recombinant adenovirus-associated virus type-2 (AAV-2) mediated interleukin-10 (IL-10) gene transfer on the expression of matrix metalloproteinase (MMP)-2, 9, tissue inhibitor of metalloproteinase (TIMP)-1, collagen type I and type III in a rat acute myocardial infarction model.
Male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 6): sham operation group, MI/AAV2 group, and MI/AAV2-IL-10 group (10(10) vg/ml x 0.1 ml injection at peri-infarct regions immediately post MI). Five days later, the expressions of MMP-2 and MMP-9 were measured by RT-PCR, Western blot and zymography. The expression of TIMP-1 was measured by RT-PCR and Western blot. Collagen type I and type III were assessed by RT-PCR and immunohistochemical stain.
The myocardial expressions of MMP-2, MMP-9 and collagen contents in MI/AAV2 group were significantly increased than those in sham operation group. Myocardial expressions of MMP-2, MMP-9 were significantly decreased and the expression of TIMP-1 significantly increased in the MI/AAV2-IL-10 group than those in MI/AAV2 group. Moreover, the expressions of collagen type I, collagen type III and the ratio of I/III collagen in border zones of infarcted myocardium were decreased by 47.6% (P < 0.01), 23.6% (P < 0.05), and 17.9% (P < 0.05) respectively, while the expression of TIMP-1 increased by 73.1%(P < 0.05) in MI/AAV2-IL-10 group compared to MI/AAV2 group.
In vivo myocardial IL-10 transfer reduced myocardial MMP and collagen expression and increasing the TIMP expression.
我们在大鼠急性心肌梗死模型中研究了重组2型腺相关病毒（AAV-2）介导的白细胞介素10（IL-10）基因转移对基质金属蛋白酶（MMP）-2、9、金属蛋白酶组织抑制剂（TIMP）-1、I型和III型胶原表达的体内影响。
雄性Sprague-Dawley（SD）大鼠随机分为三组（每组n = 6）：假手术组、MI/AAV2组和MI/AAV2-IL-10组（心肌梗死后立即在梗死周边区域注射10(10)vg/ml×0.1ml）。五天后，通过逆转录聚合酶链反应（RT-PCR）、蛋白质印迹法和酶谱法检测MMP-2和MMP-9的表达。通过RT-PCR和蛋白质印迹法检测TIMP-1的表达。通过RT-PCR和免疫组织化学染色评估I型和III型胶原。
MI/AAV2组心肌中MMP-2、MMP-9的表达及胶原含量均显著高于假手术组。与MI/AAV2组相比，MI/AAV2-IL-10组心肌中MMP-2、MMP-9的表达显著降低，TIMP-1的表达显著增加。此外，与MI/AAV2组相比，MI/AAV2-IL-10组梗死心肌边缘区I型胶原、III型胶原的表达及I/III型胶原比例分别降低了47.6%（P < 0.01）、23.6%（P < 0.05）和17.9%（P < 0.05），而TIMP-1的表达增加了73.1%（P < 0.05）。
体内心肌IL-10转移可降低心肌MMP和胶原表达，并增加TIMP表达。
