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The Therapeutic Role of Slit2 in Anti-fibrosis, Anti-inflammation and Anti-oxidative Stress in Rats with Coronary Heart Disease
Cardiovascular Toxicology ( IF 3.4 ) Pub Date : 2021-08-19 , DOI: 10.1007/s12012-021-09688-5
Ji-Wei Liu 1 , Hai-Tao Liu 2 , Lin Chen 3
Affiliation  

To investigate the efficacy of Slit2 in the rats with coronary heart disease (CHD). CHD model were constructed by feeding high-fat food and injecting with pituitrin in rat, followed by recombinant Slit2 treatment, and then the cardiac function was evaluated by echocardiography, and the indicators concerning the cardiomyocyte injury markers and lipoprotein status and oxidative stress were measured. The Slit2 expression in the heart tissues was identified by immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) was carried out to detect inflammatory cytokines, H2DCFDA staining to determine the ROS generation in heart tissues, Masson trichrome staining to observe myocardial fibrosis, and qRT-PCR and Western blotting to detect gene and protein expressions. Slit2 decreased the levels of LDH, CK-MB, cTnI, TG, TC and LDL-C and increased HDL-C level in CHD rats. In the normal heart tissues, Slit2 expression was significantly lower in cardiomyocytes than cardiac fibroblasts. Furthermore, the expressions of VCAM-1, ICAM-1, fibronectin and TGF-β1 were increased in the heart tissues of CHD rats with the obvious myocardial fibrosis, which were dose-dependently reversed by recombinant Slit2. In addition, recombinant Slit2 also dose-dependently increased the activity of NO, SOD, CAT and GSH-Px, and decreased TNF-α, IL-6, MCP-1, MDA and ROS in CHD rats. Slit2 was downregulated in myocardial tissue and plasma of CHD rats. Recombinant Slit2, by regulating the level of blood lipid, can relieve the myocardial fibrosis, inflammation and oxidative stress in CHD.



中文翻译:


Slit2对冠心病大鼠抗纤维化、抗炎和抗氧化应激的治疗作用



探讨Slit2对冠心病(CHD)大鼠的疗效。通过饲喂高脂食物并注射垂体后叶素构建大鼠冠心病模型,重组Slit2治疗后采用超声心动图评价心功能,测定心肌细胞损伤标志物、脂蛋白状态、氧化应激等指标。通过免疫荧光鉴定心脏组织中Slit2的表达。酶联免疫吸附试验(ELISA)检测炎症细胞因子 H 2 DCFDA染色测定心脏组织中ROS的生成,Masson三色染色观察心肌纤维化情况,qRT-PCR和Western blotting检测基因和蛋白表达。 Slit2 降低 CHD 大鼠的 LDH、CK-MB、cTnI、TG、TC 和 LDL-C 水平,并升高 HDL-C 水平。在正常心脏组织中,心肌细胞中Slit2的表达显着低于心脏成纤维细胞。此外,心肌纤维化明显的CHD大鼠心脏组织中VCAM-1、ICAM-1、纤连蛋白和TGF-β1的表达增加,重组Slit2可剂量依赖性地逆转这种情况。此外,重组Slit2还剂量依赖性地增加CHD大鼠中NO、SOD、CAT和GSH-Px的活性,并降低TNF-α、IL-6、MCP-1、MDA和ROS。 Slit2 在 CHD 大鼠心肌组织和血浆中表达下调。重组Slit2通过调节血脂水平,可以缓解冠心病心肌纤维化、炎症和氧化应激。

更新日期:2021-08-19
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