[Effects of overexpression of human tissue inhibitor of metalloproteinase-1 on the inflammatory response in rats with myocardial infarction and related mechanisms].

• DOI: 10.3760/cma.j.issn.0253-3758.2017.06.014
• Publication Date: 2017-06-24
• Authors: Lili Zhao; Yuxiang Song; Y Zhang; Yue Shi; Manyi Ren; S Liu; Yong-min Mao
• Keywords: Inflammation; Male; Tissue Inhibitor of Metalloproteinase-1; Interleukin-6; Tumor Necrosis Factor-alpha; Myocardium; Myocardial Infarction; Heart; Recombinant Proteins; Ventricular Function, Left; Adenoviridae; Interleukin-10; Rats; C-Reactive Protein; Echocardiography; Animals; Humans; Rats, Wistar

Objective: To observe the effects of recombinant adenovirus with human tissue inhibitor metalloproteinase-1(Ad-hTIMP-1) on inflammatory response in rats myocardial infarction (MI) and explore related mechanisms. Methods: The male Wistar were randomly divided into sham-operated group, saline Ad-Track group Ad-hTIMP-1 according to random number table (n=8 each group). MI was induced by ligation left anterior descending coronary artery injected saline, Ad-hTIMP-1, respectively. Sham-operated received similar surgical procedure without artery. After 4 weeks, cardiac function measured echocardiography, then sacrificed hearts removed for morphological biological analysis. morphology detected HE staining Masson staining. mRNA expressions tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 C-reactive protein(CRP) real-time PCR. Immune histochemical performed protein expression levels IL-6 CRP. Results: (1) Left ventricular end systolic dimension derived from echocardiography increased ((5.10±0.72) mm) ((4.88±0.64) compared ((4.25±0.46) mm), which reduced ((4.13±0.35) mm, all P<0.05). ejection fraction (72.46±5.74)%, (64.27±8.52)%, (64.65±3.90)%, (71.55±6.95)%, fractional shortening (36.90±4.97)%, (29.03±3.40)%, (30.95±2.51)%, (36.31±5.68)% lower than those (all (2) Necrosis cells not found a small amount immune cell infiltration interstitial fibrosis observed stained sections group. (3) Real-time PCR showed that TNF-α, IL-6, CRP (4) higher Conclusion: Recombinant can improve via inhibiting downregulating CRP.目的： 探讨携带人金属蛋白酶1组织抑制剂(hTIMP-1)的重组腺病毒(Ad-hTIMP-1)对大鼠心肌梗死后炎症反应的影响及机制。 方法： 将Wistar雄性大鼠按照随机数字表法分为假手术组、生理盐水组、Ad-Track组和Ad-hTIMP-1组(每组各8只大鼠)。除假手术组外，其余各组大鼠均通过结扎冠状动脉左前降支建立心肌梗死模型。生理盐水组、Ad-Track组和Ad-hTIMP-1组分别在心肌梗死部位注射生理盐水、空载体重组腺病毒(Ad-Track)和Ad-hTIMP-1。4周后以超声心动图检测各组大鼠的心功能指标，然后处死大鼠并留取心脏组织。以苏木精-伊红(HE)和Masson染色法观察各组大鼠的心肌组织形态，实时荧光定量PCR检测各组心肌组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和C反应蛋白(CRP)的mRNA表达水平，免疫组织化学法检测各组IL-6和CRP的蛋白表达水平。 结果： (1)超声心动图显示，假手术组、生理盐水组、Ad-Track组和Ad-hTIMP-1组的左心室收缩末期内径分别为(4.25±0.46)、(5.10±0.72)、(4.88±0.64)和(4.13±0.35)mm，生理盐水组和Ad-Track组均高于假手术组和Ad-hTIMP-1组(P均<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(71.55±6.95)%，短轴缩短率分别为(36.90±4.97)%、(29.03±3.40)%、(30.95±2.51)%和(36.31±5.68)%，生理盐水组和Ad-Track组的左心室射血分数和短轴缩短率均低于假手术组和Ad-hTIMP-1组(P均<0.05)。(2)HE和Masson染色显示，Ad-hTIMP-1组无心肌细胞坏死，有少量炎性细胞浸润和间质纤维化。(3)实时荧光定量PCR显示，Ad-hTIMP-1组的TNF-α、IL-6、IL-10和CRP mRNA表达水平均低于生理盐水组(P均<0.05)；Ad-hTIMP-1组的TNF-α、IL-10和CRP mRNA表达水平均低于Ad-Track组(P均<0.05)。(4)免疫组织化学法检测显示，生理盐水组和Ad-Track组的IL-6和CRP的蛋白表达水平均高于Ad-hTIMP-1组(P均<0.05)。 结论： 重组腺病毒Ad-hTIMP-1可改善大鼠心肌梗死后心功能，其机制可能与hTIMP-1抑制炎症反应，减少炎性细胞因子TNF-α、IL-6和CRP的表达有关。.