摘要
目的探讨白细胞介素10(IL-10)基因转染对大鼠急性心肌梗死(AMI)后心室纤维化重构的影响及其可能的信号转导通路。方法实验大鼠共18只,随机分为假手术组、心肌梗死(MI)-2型腺相关病毒(AAV2)组(MI-AAV2)组和MI-AAV2-IL-10转染组,每组6只。结扎大鼠左冠状动脉前降支建立AMI动物模型,应用AAV2携带IL-10基因转染心肌组织。免疫组织化学测定心肌α平滑肌肌动蛋白(α-SMA)、心肌胶原蛋白Ⅰ、Ⅲ型(Ⅰ型胶原和Ⅲ型胶原)的表达。Western blot法检测梗死、边缘和远隔区心肌磷酸化细胞外信号调节激酶(ERK1/2)和p38蛋白的表达。结果MI-AAV2-IL-10组检测到外源性IL-10 mRNA和蛋白的有效表达。免疫组织化学结果显示MI-AAV2-IL-10组较MI-AAV2组心肌α-SMA表达降低54.5%(P<0.01)。Ⅰ、Ⅲ型胶原表达分别下降了45.4%和27.4%(P<0.01),Ⅰ/Ⅲ型胶原比值下降24.6%(P<0.05)。Western blot结果显示MI-AAV2-IL-10组较MI-AAV2组心肌各部位磷酸化ERK1/2和P38蛋白的表达均下调。结论IL-10基因转染可改善大鼠AMI后心室纤维化,可能是通过影响ERK1/2和P38 MAPKs激酶通路发挥作用。
Objective To investigate the effect of IL-10 gene transfection on ventricular remodeling in rats with acute myocardial infarction（MI） and the signaling mechanism. Methods SD rats were assigned randomly into three groups： sham operation group, MI -AAV2（adenovirus associated virus 2） transfection group, and MI-AAV2-IL-10 transfection group. Rat acute infarction model was established by ligation of the anterior descending branch of left coronary artery. The expression of a-SMA, collagen type Ⅰ and type Ⅲ were assessed by immunohistochemical staining. The expression of phosphorylated ERK1/2 and p38 was measured by Western blot. Results The results of immunohistochemical staining indicated that the volume of a-SMA, collagen type Ⅰ and type Ⅲ in MI-AAV2 group increased significantly compared with sham operation group. In contrast, in the MI-AAV2-IL-10 group the three proteins decreased by 54. 5% （P 〈0. 01）, 45.4% （P〈0.01） and 27.4% （P 〈0.01）respectively, compared with MI-AAV2 group. Consistent with these,the expression of phosphorylated ERK1/2 and p38 MAPK was downregulated in MI-AAV2-IL-10 group. Conclusion IL-10 improved the deposition of collagen and myocardial fibrosis after AMI, this effect of IL-10 may be related to its regulation of ERK1/2 and p38MAPK signaling pathways.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2008年第8期610-613,共4页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金(30640083)
关键词
心肌梗塞
心室重构
白细胞介素10
转染
胶原
myocardial infarction
ventricular remodeling
interleukin-10
transfection
collagen
