Zhao L L, Song Y Q, Zhang Y, Shi Y, Ren M, Liu S, Mao Y M
Tianjin Institute of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin 300222, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2017 Jun 24;45(6):513-518. doi: 10.3760/cma.j.issn.0253-3758.2017.06.014.
To observe the effects of recombinant adenovirus with human tissue inhibitor of metalloproteinase-1(Ad-hTIMP-1) on the inflammatory response in rats with myocardial infarction (MI) and explore the related mechanisms. The male Wistar rats were randomly divided into sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group according to the random number table (=8 each group). MI was induced by ligation of the left anterior descending coronary artery and MI rats were injected with saline, Ad-Track and Ad-hTIMP-1, respectively. Sham-operated rats received similar surgical procedure without ligation of the left anterior descending coronary artery. After 4 weeks, the cardiac function was measured by echocardiography, then rats were sacrificed and hearts were removed for morphological and biological analysis. The morphology of myocardial tissue in each group was detected by HE staining and Masson staining. The mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and C-reactive protein(CRP) were detected by real-time PCR. Immune histochemical staining was performed to observe the protein expression levels of IL-6 and CRP. (1) Left ventricular end systolic dimension derived from echocardiography was increased in saline group ((5.10±0.72) mm) and Ad-Track group ((4.88±0.64) mm) compared to sham-operated group ((4.25±0.46) mm), which was reduced in Ad-hTIMP-1 group ((4.13±0.35) mm, all <0.05). The left ventricular ejection fraction was (72.46±5.74)%, (64.27±8.52)%, (64.65±3.90)%, and (71.55±6.95)%, the fractional shortening was (36.90±4.97)%, (29.03±3.40)%, (30.95±2.51)%, and (36.31±5.68)% in sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group, respectively. The left ventricular ejection fraction and fractional shortening in saline group and Ad-Track group were lower than those in sham-operated group and Ad-hTIMP-1 group (all <0.05). (2) Necrosis of myocardial cells was not found and a small amount of immune cell infiltration and interstitial fibrosis were observed on HE and Masson stained myocardial sections of Ad-hTIMP-1 group. (3) Real-time PCR showed that mRNA expressions of TNF-α, IL-6, IL-10 and CRP were lower in Ad-hTIMP-1 group than in saline group. mRNA expressions of TNF-α, IL-10 and CRP were lower in Ad-hTIMP-1 group than in Ad-Track group (all <0.05). (4) Immune histochemical staining showed that protein expressions of IL-6 and CRP were higher in saline group and Ad-Track group than those in Ad-hTIMP-1 group (all <0.05). Recombinant adenovirus Ad-hTIMP-1 can improve cardiac function in rats with myocardial infarction via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-6 and CRP.
观察携带人基质金属蛋白酶-1的重组腺病毒（Ad-hTIMP-1）对心肌梗死（MI）大鼠炎症反应的影响，并探讨其相关机制。将雄性Wistar大鼠按随机数字表随机分为假手术组、生理盐水组、Ad-Track组和Ad-hTIMP-1组（每组8只）。通过结扎左冠状动脉前降支诱导MI，MI大鼠分别注射生理盐水、Ad-Track和Ad-hTIMP-1。假手术大鼠接受类似手术操作但不结扎左冠状动脉前降支。4周后，通过超声心动图测量心功能，然后处死大鼠并取出心脏进行形态学和生物学分析。每组心肌组织形态学通过HE染色和Masson染色检测。通过实时PCR检测肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-10和C反应蛋白（CRP）的mRNA表达。进行免疫组织化学染色以观察IL-6和CRP的蛋白表达水平。（1）与假手术组（（4.25±0.46）mm）相比，生理盐水组（（5.10±0.72）mm）和Ad-Track组（（4.88±0.64）mm）超声心动图测得的左心室收缩末期内径增加，而Ad-hTIMP-1组（（4.13±0.35）mm）减小（均P<0.05）。假手术组、生理盐水组、Ad-Track组和Ad-hTIMP-1组的左心室射血分数分别为（72.46±5.74）%、（64.27±8.52）%、（64.65±3.90）%和（
