心力衰竭合并恶病质大鼠瘦素及Janus蛋白酪氨酸激酶2/信号传导与转录激活因子3信号转导通路的变化

Changes of Leptin and Janus Protein Tyrosine Kinase 2/Activating Transcriptor 3 Signal Transduction Pathways in Experimental Rats of Heart Failure With Cachexia

目的:探讨慢性心力衰竭合并恶病质大鼠血清瘦素水平的变化,并从瘦素受体表达及瘦素信号转导通路探讨其变化的原因,初步阐明心力衰竭恶病质的发生机制,为其治疗寻求新靶点。方法:60只雄性SD大鼠随机挑选15只作为对照组,其余45只大鼠通过注射异丙肾上腺素制作大鼠心力衰竭模型(ISO组,n=36,死亡9只),根据体重变化及超声心动图结果将ISO组分为心力衰竭恶病质亚组(c CHF亚组,n=16)与心力衰竭非恶病质亚组(nc CHF亚组,n=20)。酶联免疫吸附法检测各组大鼠血清瘦素、Janus蛋白酪氨酸激酶2(JAK2)、信号传导与转录激活因子3(STAT3)、细胞因子信号转导抑制因子3(SOCS3)水平;免疫组化法检测大鼠心肌、脂肪组织中瘦素受体的表达情况;逆转录聚合酶链反应(RT-PCR)法检测大鼠脂肪组织中JAK2、STAT3、SOCS3信使核糖核酸(m RNA)表达情况。结果:血清瘦素、JAK2、STAT3水平及脂肪组织JAK2、STAT3表达在nc CHF亚组和c CHF亚组明显高于对照组(P<0.05),差异有统计学意义;JAK2、STAT3水平及m RNA表达在c CHF亚组低于nc CHF亚组(P>0.05),差异无统计学意义;血清瘦素、SOCS3水平及SOCS3 m RNA表达在c CHF亚组低于nc CHF亚组(P<0.05),差异有统计学意义;瘦素受体在大鼠心肌、脂肪组织中的表达,c CHF亚组均高于nc CHF亚组和对照组(P<0.05),差异有统计学意义,nc CHF亚组高于对照组(P<0.05),差异有统计学意义。结论:高瘦素水平参与心力衰竭的发生,且瘦素水平与受体表达及其JAK2/STAT3信号通路相关蛋白表达的变化相关;瘦素的JAK2/STAT3信号通路可能参与心力衰竭恶病质的发生。

Objective： To investigate the changes of serum levels of leptin in chronic heart failure （CHF） rats with caehexia and to study its mechanism via leptin receptor expression and leptin signal transduetion pathways. Methods： There were 15/60 male SD rats were randomly used as Control group. CHF model was established in rest 45 rats by isoproterenol hydrochloride （ISO） injection as CHF group, n=36; 9 rats died. According to body weight changes and echocardiography examination, CHF rats were further divided into 2 groups： eCHF group, the rats with eaehexia, n=16 and ncCHF group, the rats with non-cachexia, n=20. Serum levels of leptin and protein levels of janus activating kinase 2 （JAK2）, signal transducer and activator of transcription 3 （STAT3）, suppressor of cytokine signaling 3 （SOCS3） were examined by ELISA; the expressions of leptin receptor in the myocardial and adipose tissues were observed by immunohistochemistry; mRNA expressions of JAK2, STAT3 and SOCS3 in adipose tissue were detected by RT-PCR. Results： Serum levels of leptin, JAK2, STAT3 and the expressions of JAK2, STAT3 in adipose tissue were higher in both ncCHF and cCHF groups than Control group, P〈0.05; protein levels and mRNA expressions of JAK2 and STAT3 were similar between cCHF group and ncCHF group, P〉0.05. Serum levels of leptin, SOCS3 and mRNA expression of SOCS3 in cCHF group were lower than ncCHF group, P〈0.05. The expressions of leptin receptor in myocardial and adipose tissue were higher in cCHF group than ncCHF group, P〈0.05, while the expressions in ncCHF group were higher than Control group, P〈0.05. Conclusions： Increased serum level of leptin was involved in HF occurrence, leptin receptor expression and JAK2/ STAT3 signal transduction pathways might be related to CHF combining cachexia in experimental rats.