Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.
Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.
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抑制环加氧酶 2 可减少阿霉素诱发心力衰竭大鼠的下丘脑兴奋
DOI：
10.1371/journal.pone.0048771
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Qin DN
中科院分区：
文献类型：
--
作者：
Zheng M;Kang YM;Liu W;Zang WJ;Bao CY;Qin DN
下丘脑室旁核（PVN）在心力衰竭（HF）的进展中起重要作用。我们研究了在室旁核抑制环氧合酶 - 2（COX - 2）是否会减弱阿霉素诱导的心力衰竭大鼠的交感神经系统（SNS）和肾素 - 血管紧张素系统（RAS）的活性。
通过在2周内腹腔注射阿霉素（累计剂量为15 mg/kg）诱导心力衰竭。在第19天，大鼠每天接受胃内给予COX - 2抑制剂塞来昔布（CLB）或生理盐水。CLB治疗降低了HF大鼠的死亡率，并减轻了心肌萎缩和肺淤血。与HF大鼠相比，HF + CLB大鼠的心重与体重比（VW/BW）、肺重与体重比（LW/BW）、心率（HR）、左心室舒张末期压力（LVEDP）、左心室收缩期峰值压力（LVPSP）以及左心室压力最大变化率（LV±dp/dtmax）均得到改善。HF大鼠室旁核中的血管紧张素II（ANG II）、去甲肾上腺素（NE）、COX - 2和谷氨酸（Glu）增加。HF大鼠血浆中ANG II和NE水平较高，心肌中ANG II水平较高，血浆和心肌中的心钠素（ANP）水平较低。CLB治疗减轻了这些由HF引起的变化。与对照大鼠相比，HF大鼠室旁核中COX - 2阳性神经元和促肾上腺皮质激素释放激素（CRH）阳性神经元更多。CLB治疗减少了HF大鼠室旁核中的COX - 2阳性神经元和CRH阳性神经元。
这些结果表明，室旁核COX - 2可能是室旁核神经元激活和兴奋性神经递质释放的中间步骤，这进一步导致了阿霉素诱导的心力衰竭中的交感兴奋和RAS激活。COX - 2抑制剂治疗可减弱阿霉素诱导的心力衰竭中的交感兴奋和RAS激活。
Background The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure. Methodology/Principal Finding Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg). On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB) or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW) and lung to body weight (LW/BW) ratios, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak systolic pressure (LVPSP) and maximum rate of change in left ventricular pressure (LV±dp/dtmax) were improved in HF+CLB rats. Angiotensin II (ANG II), norepinephrine (NE), COX-2 and glutamate (Glu) in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH) positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. Conclusions These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.
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影响因子：
3.2
作者：
Oldfield, BJ;Davern, PJ;McKinley, MJ
通讯作者：
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影响因子：
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作者：
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通讯作者：
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