张昕 ，石翠翠

作者单位：014010 内蒙古自治区包头市，包头医学院第一附属医院 心血管内科



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

张昕 ，石翠翠

作者单位：014010 内蒙古自治区包头市，包头医学院第一附属医院 心血管内科

摘要

关键词心力衰竭；瘦素；受体；信号转导

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

ZHANG Xin, SHI Cui-cui.
Department of Cardiology, First Affiliated Hospital of Baotou Medical College, Baotou (014010), Inner Mongolia, China
Corresponding Author: SHI Cui-cui, Email: 243821336@qq.com

Abstract

Objective: To investigate the changes of serum levels of leptin in chronic heart failure (CHF) rats with cachexia and to study its mechanism via leptin receptor expression and leptin signal transduction 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: cCHF group, the rats with cachexia, 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 similarbetween 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.

Key words Heart failure; Leptin; Recptors; Signal transduction pathway

(Chinese Circulation Journal, 2016,31:82.)

慢性心力衰竭（CHF）是各种心脏疾病发展到终末期共同的临床表现，据人群流行病学调查，其发病率约为3‰～20‰[1]。除心功能减低、心脏结构异常等表现外，往往出现不同程度的机体消耗。随着脂肪组织和骨组织减少到一定程度就会出现心力衰竭恶病质（cCHF），以体重下降、低营养状态为特征，表现为厌食、消瘦、乏力等。研究发现这与患者的脂肪组织分解、肌肉萎缩等相关[2]，瘦素（LEP）在此过程中发挥重要作用。瘦素与特异受体-瘦素受体（Ob-R）结合，主要作用于下丘脑[3]，通过信号转导途径发挥其生物学效应[4]。Janus蛋白酪氨酸激酶2/信号传导与转录激活因子3（JAK2/STAT3）途径目前被认为是瘦素信号转导的主要途径[5]。本研究探讨cCHF大鼠血清瘦素变化的原因，并从Ob-R表达情况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。

1　材料与方法

建立大鼠心力衰竭模型： 2014-04选用10～12周龄雄性SD大鼠60只，体重280～300 g，随机抽取45只腹股沟皮下注射异丙肾上腺素（大连美仑生物有限公司提供）建立心力衰竭模型（ISO组，n=36，死亡9只）。具体方法：ISO的配制终浓度为20 mg/ml，按180 mg/（kg·d），隔日一次，共2次注射到大鼠腹股沟皮下，所有大鼠用药后正常进食和活动，饲养4周。……