过刊浏览

雌激素通过调节Gαs-cAMP通路减轻异丙肾上腺素导致的大鼠心肌损伤

桑黎黎, 周春乐, 付璐, 种静敏, 张琳, 曹先存, 孙红^*

徐州医学院生理学教研室，徐州 221004

摘要

本研究旨在通过给予去卵巢大鼠异丙肾上腺素制作心肌损伤及心功能异常模型，探讨雌激素通过调节兴奋性G (Gαs)蛋白-环磷酸腺苷(cAMP)信号通路纠正儿茶酚胺导致的心功能异常的机制。观察雌激素对大鼠血流动力学参数：左心室收缩峰压(LVSP)、左心室舒张末压(LVEDP)、左心室内压上升的最大变化速率(+dp/dtmax)、左心室内压下降的最大变化速率(−dp/dtmax)，血浆脑尿钠肽(brain natriuretic peptide, BNP)，cAMP浓度和心肌中Gαs蛋白表达的影响。结果显示：与假手术组相比，去卵巢大鼠的血流动力学参数、血浆BNP水平、血浆cAMP水平没有显著改变；但给予去卵巢大鼠异丙肾上腺素后，血流动力学参数LVSP、+dp/dtmax降低(P < 0.01)，LVEDP、−dp/dtmax升高(P < 0.01)，血浆BNP水平升高(P < 0.01)，血浆cAMP 水平降低(P < 0.01)；而进一步的雌激素补充则改善了心功能：LVSP、+dp/dtmax升高(P < 0.01)，LVEDP、−dp/dtmax降低(P < 0.05，P < 0.01)，血浆BNP水平降低(P < 0.01)，cAMP水平升高(P < 0.01)；雌激素对Gαs蛋白表达没有显著影响。结果提示：雌激素对心肌损伤具有保护作用，升高cAMP 水平，改善心肌收缩过度抑制，调节心脏的功能状态。

关键词： 雌激素; 异丙肾上腺素; Gαs蛋白; cAMP

分类号：R33

[Estrogen reduced myocardial damage by regulating Gαs-cAMP pathway in isoprenaline injured rats.] [Article in Chinese]

SANG Li-Li, ZHOU Chun-Le, FU Lu, CHONG Jing-Min, ZHANG Lin, CAO Xian-Cun, SUN Hong^*

Department of Physiology, Xuzhou Medical College, Xuzhou 221004, China

Abstract

The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G α protein (Gαs)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17β-estradiol given group (OVX+E2), OVX and isoprenaline injected group (OVX+ISO), OVX and 17β-estradiol, isoprenaline injected group (OVX+E2+ISO). Rats were ovariectomized, and two weeks later, OVX+E2 group was injected with E2, OVX+ISO group was injected with ISO, OVX+E2+ISO group was injected with E2 and ISO. Another four weeks later, the hemodynamic parameters were monitored by carotid artery intubation: left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal differentials of left ventricular developed pressure (+dp/dtmax), and minimal differentials of left ventricular developed pressure (−dp/dtmax). Brain natriuretic peptide (BNP) and cAMP concentration in plasma were determined; Gαs protein expression in myocardium was determined. The results showed that the hemodynamic parameters, the concentration of BNP and cAMP in plasma had no significant changes after ovariectomy compared with sham group. But after isoprenaline injection in ovariectomized rats, LVSP and +dp/dtmax declined (P < 0.01), LVEDP and −dp/dtmax elevated (P < 0.01); plasma BNP concentration increased (P < 0.01); plasma cAMP concentration decreased (P < 0.01), compared with OVX group. Further estrogen supplements improved the heart function treated by isoprenaline: LVSP and +dp/dtmax elevated (P < 0.01), LVEDP and −dp/dtmax declined (P < 0.05, P < 0.01); the plasma BNP concentration decreased (P < 0.01); the plasma cAMP concentration increased (P < 0.01). Estrogen had no significant influence on Gαs protein expression. The results suggest that estrogen can alleviate myocardial injury and regulate cardiac function disorder by increasing cAMP level, finally improved the excessive suppression of myocardium.

Key words: Estrogen; isoprenaline; Gαs protein; cAMP

收稿日期：2014-02-28　　录用日期：2014-04-30

通讯作者：孙红　　E-mail: sunh@xzmc.edu.cn

引用本文：

桑黎黎, 周春乐, 付璐, 种静敏, 张琳, 曹先存, 孙红. 雌激素通过调节Gαs-cAMP通路减轻异丙肾上腺素导致的大鼠心肌损伤[J]. 生理学报 2014; 66 (5): 583-588.

SANG Li-Li, ZHOU Chun-Le, FU Lu, CHONG Jing-Min, ZHANG Lin, CAO Xian-Cun, SUN Hong. [Estrogen reduced myocardial damage by regulating Gαs-cAMP pathway in isoprenaline injured rats.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (5): 583-588 (in Chinese with English abstract).