白细胞介素-37对小鼠心力衰竭的抑制作用

Therapeutic effects of interleukin-37 in mouse heart failure and its mechanism

目的研究白细胞介素(interleukin,IL)-37对小鼠心力衰竭的作用及其机制。方法将小鼠随机分成正常对照组、模型组(每天腹腔给予15 mg/kg异丙肾上腺素,连续9 d)、阴性对照组(隔天同时腹腔注射Ig G蛋白1μg)和实验组(隔天同时腹腔注射重组人IL-37蛋白1μg)。9 d后检测小鼠心脏功能参数,HE染色观察心脏病理学变化,q PCR与酶联免疫吸附测定检测小鼠心肌细胞细胞因子m RNA和蛋白的表达。结果与正常对照组相比,模型组中小鼠心脏功能受损(P<0.05),心肌组织出现局部水肿和炎性细胞浸润且心肌肌纤维排列紊乱,同时IL-17和肿瘤坏死因子(tumor necrosis factor,TNF)-α的表达升高(P<0.05),IL-10的表达降低(P<0.05);与模型组相比,实验组中小鼠心脏功能显著改善(P<0.05)且其心肌肌纤维排列相对整齐,炎性细胞浸润明显减少,同时IL-17和TNF-α的表达明显降低(P<0.05),IL-10的表达显著升高(P<0.05)。结论 IL-37对小鼠心力衰竭具有抑制作用,可能是通过下调促炎因子IL-17和TNF-α的表达,上调抗炎因子IL-10的表达发挥作用的。

Studies have shown that the plasma level of IL-37 is correlated with the severity of heart failure. This study designed to investigate the function and mechanism of interleukin （IL）-37 in mouse heart failure. Mice （clean class） were randomly divided into four groups： control group （NS group）, heart failure group （HF group）, negative control group （IgG group）, and experimental group （rhIL-37 group）. These mice were intraperitoneally given 15 mg/（kg· d） isoproterenol for 9 days to establish the heart failure model except the mice of NS group, rhIL-37 group mice were intraperitoneally injected recombinant human IL-37 protein （1μg） every other day, while the mice of IgG group were received IgG protein （1 μg）. The mice in HF group were given the same amount of normal saline. Cardiac function parameters of the mice were evaluated. HE staining was used to observe mouse heart pathological changes; qPCR and enzyme linked immunosorbent assay （ELISA） were employed to analyze cytokine expression of cardiomyocytes in mice of each group nine days later. Data showed that compared with the mice of NS group, the heart of mice in HF group showed damaged cardiac function （P〈0.05）, local edema, inflammatory cells infiltration, the disordered arrangement of myocardial fibers, the lower expression of IL-10 （P〈0.05）, and the higher expression of IL-17 and TNF-α （P〈0.05）; compared with the mice of HF group, the mice in rhIL-37 group showed a sustained improvement of cardiac function （P〈0.05）, the amelioration of cardiac muscle cells arrangement, the reduction of inflammatory cells infiltration, the higher expression of IL-10 （P〈0,05）, and the lower expression of IL-17 and TNF-α （P〈0.05）. In conclusion, IL-37 can inhibit heart failure, and the mechanism may relate with down-regulating the expression of IL- 17 and TNF-α, up-regulating IL- 10 expression.