下丘脑室旁核CRH神经元激活在慢性充血性心力衰竭中的交感兴奋作用  

Activation of corticotrophin releasing hormone-containing neurons in hypothalamic paraventricular nucleus contributes to sympathoexcitation in rats with congestive heart failure

作　　者：郭艳琳[1] 张华屏[2] 杨彩红[3] 吕豆 康玉明[4] 

机构地区：[1]山西医科大学病理学教研室,山西太原030001 [2]山西医科大学转化医学研究中心,山西太原030001 [3]山西医科大学药理学教研室,山西太原030001 [4]西安交通大学医学院病理与病理生理学教研室,陕西西安710061

出　　处：《中国病理生理杂志》2017年第7期1219-1225,共7页Chinese Journal of Pathophysiology

基　　金：山西省自然科学基金资助项目(No.2014011043-6);山西医科大学博士启动基金项目(No.03201101);山西医科大学基础医学院331基础医学科技培植基金项目(No.201412)

摘　　要：目的:观察慢性心衰时下丘脑室旁核(PVN)内促肾上腺皮质激素释放激素(CRH)表达变化及其与交感神经活动之间的关系。方法:健康雄性SD大鼠,冠脉结扎制备心衰模型,侧脑室插管渗透压泵持续给药。假手术组和心衰组给予人工脑脊液0.25μL/h,心衰给药组给予CRH抑制剂αh-CRH 15 mg/h。同时,选取健康雄性体内CRH合成不足的Lewis大鼠与同源纯种Fischer 344大鼠分别制备心衰模型和假手术对照进行对比研究。4周后,测定左室舒张末压(LVEDP)、左室内压最大上升和下降速率(±dp/dtmax)、右心室/体重比(RV/BW)、肺/体重比(lung/BW)、肾交感神经放电活动(RSNA)、血浆去甲肾上腺素(NE)浓度和PVN内CRH阳性神经元数目。血浆促肾上腺皮质激素(ACTH)含量。结果:与假手术组相比,SD心衰大鼠PVN内CRH阳性神经元数目明显增加,血浆ACTH浓度升高,RSNA增强,血浆NE浓度增加,LVEDP、lung/BW和RV/BW增加,±dp/dtmax降低;心衰模型后给予αh-CRH可明显逆转上述各种变化(P<0.05)。Fisher 344大鼠心衰组和假手术对照相比,PVN内CRH阳性神经元数目明显增加,血浆ACTH浓度升高,RSNA增强,外周血NE浓度升高,LVEDP、RV/BW和lung/BW增加,±dp/dtmax下降(P<0.05)。但Lewis大鼠心衰组和假手术对照相比,以上各指标改变均不明显。结论:慢性心衰时,下丘脑室旁核CRH神经元被激活,激活的CRH神经元可增强外周交感神经活动,加重心功能恶化。AIM： To observe the expression of corticotropin releasing hormone （CRH） within the paraventricu-lar nucleus of hypothalamus （ PVN） and to explore the relationship between the activated CRH-containing neurons and sym-pathetic activity in rats with heart failure （HF）. METHODS： Healthy male Sprague-Dawley （SD） rats were subjected to coronary artery ligation to induce HF, and chronic intracerebroventricular （ICV） infusion was performed by osmotic pump for 4 weeks. The rats in sham group and HF group were given vehicle （VEH; artificial cerebrospinal fluid 0.2 5μL/h）. The rats in HF plus treatment group were treated with CRH competitive inhibitor ah-CRH （15 mg/h）. Meanwhile, the Lewis rats and Fischer 344 rats for control study also underwent coronary ligation to induce HF or sham surgery. After 4 weeks, left ventricular end-diastolic pressure （ LVEDP） and maximum positive/negative change in pressure over time （± dp/dtmax） were determined. The right ventricular-to-body weight （RV/BW） and lung-to-body weight （lung/BW） ratios were calculated. The renal sympathetic nerve activity （ RSNA） was recorded and the plasma norepinephrine （ NE） level was measured. The expression of CRH in the PVN combined with the plasma adrenocorticotrophic hormone （ACTH） levels were measured. RESULTS： Compared with the sham-SD rats, the HF-SD rats had a greater number of CRH positive neu-rons in the PVN （accordingly the plasma ACTH levels were increased） , accompanied by decreased ± dp/ dtmax and in-creased RSNA, plasma NE, LVEDP, lung/BW and RV/BW. However, ICV treatment with ah-CRH attenuated these changes in the HF-SD rats （P 〈0. 05） . Compared with the sham-Fisher 344 rats, the HF-Fisher 344 rats also had a grea-ter number of CRH positive neurons in the PVN （accordingly the plasma ACTH levels were increased）. In addition, they had significantly increased RSNA and plasma NE level, higher LVEDP, RV/BW and lung/BW, and lower ± dp/d

关 键 词：慢性充血性心力衰竭 下丘脑室旁核 促肾上腺皮质激素释放激素-神经元 交感神经系统 LEWIS大鼠 Fisher 344大鼠 

分 类 号：R541.61[医药卫生—心血管疾病] R363[医药卫生—内科学]