白介素17在病毒性心肌炎和扩张型心肌病中的作用

Role of interleukin 17 in viral myocarditis and dilated cardiomyopathy

目的通过检测病毒性心肌炎(VMC)小鼠和扩张型心肌病(DCM)患者的白介素17(IL-17)表达变化,研究IL-17在VMC和DCM中的表达。方法100只雄性4周龄BALB/c小鼠分为VMC组(80只)和对照组(20只),以柯萨奇病毒B3(CVB3)感染小鼠建立VMC模型,RT-PCR法检测各时期小鼠脾细胞IL-17mRNA表达水平,免疫组织化学法检测室肌组织IL-17蛋白表达。另选择30例DCM患者(DCM组),26例非DCM心脏病患者(非DCM组)及20例正常人(NC组),酶联免疫吸附法(ELISA)检测人血浆及外周血单个核细胞(PBMC)体外培养液中IL-17含量,并用RT-PCR法测定PBMC的IL-17mRNA表达。结果VMC小鼠脾细胞IL-17mRNA在2周时无表达,4周后有表达,4及6周时表达均明显高于8周(P<0.01)。VMC小鼠在2周时心室肌组织无IL-17蛋白表达,4周时心室肌组织中IL-17蛋白表达最高,6周至8周呈明显下降趋势(P<0.01)。DCM组、非DCM组和NC组的血浆、PBMC自发培养上清液IL-17水平无显著性差异(P>0.05),但经植物抗血凝素(PHA)刺激培养后,DCM组PBMC培养上清液IL-17水平明显高于非DCM组和NC组(P<0.01)。在DCM组、非DCM组和NC组直接提取及培养无刺激的PBMC中均无IL-17mRNA表达,经PHA刺激后DCM组PBMC中IL-17mRNA表达明显高于非DCM组和NC组(P<0.05)。结论小鼠病毒性心肌炎慢性期及扩张型心肌病患者IL-17表达明显增高,提示IL-17可能在VMC和DCM发病过程中起重要作用。

Objective To explore the role of interleukin-17 （IL-17） in the evolution of viral myocarditis （VMC） into dilated cardiomyopathy （DCM）. Methods A mouse model of VMC was established in 100 male Balb/c mice by intraperitoneal injection of coxsackievirus B3. The expression of IL-17 protein in the cardiac tissue of the mice was detected immunohistochemically, and IL-17 mRNA in the splenocytes was examined by reverse transcription-polymerase chain reaction （RT-PCR）. IL-17 levels in the plasma, peripheral blood mononuclear cell （PBMC） culture supernatants, and phytohemagglutinin （PHA）-stimulated PBMC culture supematants were measured in 30 DCM patients, 26 non-DCM patients and 20 normal adults using enzyme-linked immunosorbent assay （ELISA）, and IL-17 mRNA expression in the PBMCs was detected using RT-PCR. Results The levels of IL-17 mRNA in the splenocytes of the mice with VMC were significantly higher at 4 and 6 weeks than those at 8 weeks （P〈0.01）, but not detected at 2 weeks. No IL-17 expression was found in the ventricular tissue of the mice at 2 weeks, but peaked at 4 weeks followed by gradual decrease （P〈0.01）. IL-17 level in PHA-stimulated PBMC culture supernatants but not the plasma, and its mRNA level in PHA-stimulated PBMCs but not the PBMC culture supernatants, were significantly elevated in DCM patients as compared with those in non-DCM patients and normal control subjects. Conclusion The mouse model of VMC in the chronic phase and DCM patients express high levels of IL-17, which may contribute to the transition from VMC to DCM.