白细胞介素9在异丙肾上腺素致心肌肥厚中的作用及机制研究

Role of IL-9 in isoproterenol induced cardiac hypertrophy and mechanism

目的探讨白细胞介素(IL)-9在异丙肾上腺素(ISO)致心肌肥厚中的作用及机制研究。方法选择SPF级C57BL/6雄性小鼠40只,随机分成为4组:对照组、ISO组、中和抗体(mAb)组(ISO+mAb)和IgG组(ISO+IgG),每组10只小鼠。通过微量渗透泵置入持续静脉滴注ISO构建小鼠心肌肥厚模型,其中ISO组按30 mg/(kg·d)静脉滴注ISO,对照组静脉滴注等量生理盐水。mAb组和IgG组分别腹腔注射IL-9 mAb(100μg/周)和同型IgG对照(100μg/周)。术后14 d,使用超声心动图评估心脏功能,测量左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、LVEF和左心室短轴缩短率(LVFS)。测量小鼠体质量(BW),心脏质量(HW),胫骨长度(TL),计算HW/BW比值和HW/TL比值。同时行苏木精-伊红染色和麦胚凝集素(WGA)染色。RT-PCR检测小鼠心肌组织IL-1、IL-6、IL-17和TNF-αmRNA表达。结果与对照组比较,ISO组LVEDD、LVESD、HW、HW/BW和HW/TL明显升高,LVEF和LVFS明显降低(P<0.05)。与ISO组比较,mAb组LVEDD、LVESD、HW、HW/BW和HW/TL明显降低,LVEF和LVFS明显升高(P<0.05)。与对照组比较,ISO组IL-1、IL-6、IL-17和TNF-αmRNA表达明显升高,差异有统计学意义(P<0.05)。与ISO组比较,mAb组IL-1、IL-6、IL-17和TNF-αmRNA表达明显降低(2.37±0.22 vs 4.24±0.33,1.87±0.16 vs 3.22±0.23,2.42±0.29 vs 3.51±0.36,1.54±0.16 vs 2.97±0.23,P<0.05)。结论中和内源性IL-9可显著降低心脏炎症,改善ISO引起的心肌肥厚。

Objective To study the role of IL-9 in isoproterenol(ISO)-induced cardiac hypertrophy and its mechanism.Methods Forty male SPF C57 BL/6 mice were randomly divided into control group,ISO group,mAb group(ISO+mAb)and IgG group(ISO+IgG)with 10 in each group.A cardiac hypertrophy model of mice was established by continuous intravenous ISO drip via a micro osmotic pump.The animals in ISO group received intravenous ISO drip 30 mg/(kg·d)and those in IgG group received an equivalent normal saline intravenous drip,those in mAb group and IgG group received intraperitoneal injection with IL-9 mAb(100μg/week)and homotypic IgG(100μg/week)respectively.The cardiac function was evaluated by echocardiography,the LVESD and LVEDD were measured,and the LVEF,LVFS,body weight(BW),heart weight(HW),tibia length(TL),HW/BW ratio,HW/TL ratio were calculated on day 14 after operation.The expressions of IL-1,IL-6,IL-17 and TNF-αmRNA were detected by RT-PCR with HE staining and WGA staining respectively.Results The LVEDD and LVESD were significantly longer,and the HW,HW/BW ratio and HW/TL ratio were significantly higher while the LVEF and LVFS were significantly lower in ISO group than in control group(P<0.05).The LVEDD and LVESD were significantly shorter,and the HW,HW/BW ratio and HW/TL ratio were significantly lower while the LVEF and LVFS were significantly higher in mAb group than in ISO group(P<0.05).The myocardiac hypertrophy was significantly milder in mAb group than in ISO group(P<0.05).The expression levels of IL-1,IL-6,IL-17 and TNF-αmRNA were significantly higher in ISO group than in control group(P<0.05)and significantly lower in mAb group than in ISO group(2.37±0.22 vs 4.24±0.33,1.87±0.16 vs 3.22±0.23,2.42±0.29 vs 3.51±0.36,1.54±0.16 vs 2.97±0.23,P<0.05).Conclusion Neutralization of endogenous IL-9 can effectively reduce the cardiac inflammation and improve the ISO-induced myocardial hypertrophy in mice.