Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, Changsha, China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6283-6291. doi: 10.26355/eurrev_201907_18450.
To investigate the effects of interleukin-6 (IL-6) gene knockout on myocardial remodeling after myocardial infarction (MI) in mice and the potential mechanism, to provide certain references for the prevention and treatment of MI in clinic.
A total of 40 male C57 mice were divided into two groups, namely Sham group (n=20) and MI group (n=20), using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into the MI + IL-6 KO group. The MI model was established by means of ligating the left anterior descending coronary artery of the mice. 28 d later, the survival status of the three groups of mice was recorded. In addition, the cardiac functions of each group of mice, including two-dimensional echocardiography, ejection fraction (EF%) and fractional shortening (FS%), were measured. The cross-sectional area and pathological change of the myocardial cells in cardiac tissues of each group of mice were detected via hematoxylin and eosin (H&E) staining. Immunohistochemistry was applied to determine the expression of tumor necrosis factor-alpha (TNF-α) in each group of mouse cardiac tissues. Moreover, immunofluorescent staining was utilized to measure the content of M2 macrophages in each group of mouse cardiac tissues.
The 28-d survival rate of the mice with IL-6 gene knockout was remarkably higher than that of the wild-type mice (p<0.05). Furthermore, the cardiac functions of the mice in the MI + IL-6 KO group were superior to those in the MI group, with markedly improved FS% and EF% (p<0.05). According to the H&E staining results, the cross-sectional areas of the heart and myocardial cells were decreased notably in MI + IL-6 KO group compared with those in the MI group (p<0.05). The immunohistochemical staining results showed that IL-6 knockout could lower the MI-induced high expression of TNF-α (p<0.05), and Masson's trichrome staining indicated that IL-6 knockout could also repress the degree of cardiac fibrosis. Moreover, it was discovered through immunofluorescent staining that the mice in the MI + IL-6 KO group had markedly elevated content of M2 macrophages in cardiac tissues than those in the MI group (p<0.05).
Inhibiting IL-6 gene expression can prominently ameliorate the MI-induced myocardial remodeling, whose mechanism is possibly associated with the activation of M2 macrophages and reduced collagen production in fibroblast cells.
探讨白细胞介素-6（IL-6）基因敲除对小鼠心肌梗死后心肌重构的影响及其潜在机制，为临床防治心肌梗死提供一定参考。
将 40 只雄性 C57 小鼠采用随机数字表法分为假手术组（n=20）和心肌梗死组（n=20）。另将 20 只 IL-6 基因敲除小鼠纳入 MI+IL-6KO 组。结扎小鼠左前降支建立心肌梗死模型。28 d 后，记录三组小鼠的生存状态。此外，通过二维超声心动图测量各组小鼠的心功能，包括射血分数（EF%）和短轴缩短率（FS%）。通过苏木精-伊红（H&E）染色检测各组小鼠心肌组织的心肌细胞横截面积和病理变化。采用免疫组织化学法检测各组小鼠心肌组织中肿瘤坏死因子-α（TNF-α）的表达。此外，采用免疫荧光染色法测量各组小鼠心肌组织中 M2 巨噬细胞的含量。
IL-6 基因敲除小鼠的 28 d 生存率明显高于野生型小鼠（p<0.05）。此外，MI+IL-6KO 组小鼠的心功能明显优于 MI 组，FS%和 EF%明显升高（p<0.05）。根据 H&E 染色结果，MI+IL-6KO 组小鼠的心脏和心肌细胞的横截面积明显小于 MI 组（p<0.05）。免疫组织化学染色结果显示，IL-6 基因敲除可降低 MI 诱导的 TNF-α高表达（p<0.05），Masson 三色染色显示，IL-6 基因敲除还可抑制心肌纤维化程度。此外，免疫荧光染色显示，MI+IL-6KO 组小鼠心肌组织中 M2 巨噬细胞含量明显高于 MI 组（p<0.05）。
抑制 IL-6 基因表达可显著改善 MI 诱导的心肌重构，其机制可能与 M2 巨噬细胞的激活和减少成纤维细胞胶原生成有关。
