大鼠孤束核内salusin α中枢心血管效应机制研究

发布时间：2018-05-30 00:28

本文选题：salusin + 大鼠　；参考：《兰州大学》2012年硕士论文

【摘要】：近年来研究资料表明,高血压、动脉粥样硬化等心血管疾病与心血管活性肽的作用呈高度的相关性。血管紧张素、内皮素等一系列心血管活性肽的发现,丰富了高血压、动脉粥样硬化等心血管疾病的研究理论,由此催生出一批新的临床治疗药物,提高了高血压、动脉粥样硬化等心血管疾病的治疗效果,改善了患者的生活质量。 Salusins是从已经完成的人类基因组计划的基因文库中,根据表达序列标记的开放阅读框架预测的肽类物质中筛选的,主要存在于造血系统、内分泌系统和中枢神经系统,是具有降低血压和丝裂原样效应的生物活性肽。成熟的salusins由20个氨基酸组成的salusin α和28个氨基酸组成的salusin β两种活性单体组成。salusin α广泛分布于人和大鼠的骨髓、内分泌腺和脑组织,具有降低血压、减缓心率等生物学效应,可能参与高血压、动脉粥样硬化等心血管疾病的发生过程。脑室内salusins对大鼠心血管活动产生的调节作用,已有文献报道。延髓是心血管活动调节的基本中枢。孤束核(nucleus tractus solitarii, NTS)作为延髓的重要组成部分,在心血管活动调节过程中发挥着重要作用。salusin α在大鼠孤束核是否对心血管活动有调节作用及其机制研究尚不清楚。所以本研究主要探讨孤束核内salusin α的心血管效应及其机制。实验选用雄性SD大鼠,体重250～300g。实验分组为：1.双侧NTS给药组：以人工脑脊液(aCSF)为对照,在大鼠双侧NTS分别微量注射不同剂量salusin α,观察对血压和心率的影响。2.单侧NTS给药组：在大鼠单侧NTS分别微量注射不同剂量salusin α,观察对血压和心率的影响。3.动脉压力感受性反射组：以aCSF为对照,双侧NTS微量注射salusin α,观察对动脉压力感受性反射功能的影响。4.机制组：预先分别在单侧NTS注射非选择性谷氨酸受体拮抗剂犬尿烯酸(kynurenic acid, KYN)、头端延髓腹外侧区(rostral ventrolateral medulla, RVLM)预先注射γ-氨基丁酸(gamma-aminobutyric acid, GABA)激动剂musciml、行双侧迷走神经切除术,10min后在大鼠单侧NTS分别微量注射salusin α,探讨NTS内salusin α心血管效应机制。各组的正常对照均为在相应的部位注射同等量的人工脑脊液(aCSF)。实验结果提示在NTS双侧或单侧微量注射salusin α,可剂量依赖性的降低大鼠血压,减缓心率。双侧NTS微量注射salusin α不影响麻醉大鼠的动脉压力感受性反射。NTS预先注射非选择性谷氨酸受体拮抗剂KYN或双侧迷走神经切除均不影响salusin α产生的降低血压和减缓心率效应(P0.05)。RVLM预先注射γ-氨基丁酸(GABA)激动剂muscimol(10g·L-1)能有效阻断salusin α在NTS内产生的降低血压和减缓心率效应(P0.05)。综上所述,NTS注射salusin α产生的降低血压、减缓心率的效应可能间接通过激动RVLM内GABA受体,抑制前交感神经元兴奋性发挥作用。
[Abstract]:Recent studies have shown that cardiovascular diseases such as hypertension and atherosclerosis are highly correlated with the action of cardiovascular active peptides. The discovery of angiotensin, endothelin and a series of cardiovascular active peptides enriches the research theory of cardiovascular diseases such as hypertension, atherosclerosis, etc. The therapeutic effect of cardiovascular diseases such as atherosclerosis improves the quality of life of patients. Salusins is screened from the gene library of the completed Human Genome Project and predicted peptides based on the open reading framework for expression sequence markers, mainly in the hematopoietic, endocrine and central nervous systems. It is a bioactive peptide with the effects of lowering blood pressure and mitosis. Mature salusins is composed of 20 amino acids salusin 伪 and 28 amino acids salusin 尾. Salusin 伪 is widely distributed in bone marrow, endocrine gland and brain tissue of human and rats. It has biological effects such as lowering blood pressure and slowing heart rate. May be involved in hypertension, atherosclerosis and other cardiovascular disease process. The regulatory effects of ventricular salusins on cardiovascular activity in rats have been reported. Medulla oblongata is the basic center of cardiovascular regulation. As an important part of the medulla oblongata, tractus solitarii, NTS) plays an important role in the regulation of cardiovascular activity. Therefore, the cardiovascular effect and mechanism of salusin 伪 in the nucleus tractus solitarii were studied in this study. Male Sprague-Dawley rats were selected. The experiment was divided into 1: 1. Bilateral NTS group: the control group was given artificial cerebrospinal fluid (ACSF). Bilateral NTS was microinjected with different dosages of salusin 伪 to observe the effect of salusin 伪 on blood pressure and heart rate. Unilateral NTS group: rats were given microinjection of different doses of salusin 伪 into unilateral NTS to observe the effects on blood pressure and heart rate. Arterial baroreflex group: bilateral NTS was microinjected with salusin 伪 to observe the effect of salusin 伪 on arterial baroreflex function. The mechanism group: the non-selective glutamate receptor antagonists kynurenic acidic, KYNN, and rostral ventrolateral medulla, RVLM) of ventrolateral medulla oblongata were injected with musciml of gamma-aminobutyric acid (GABA) agonist in unilateral NTS, and bilateral vagotomy was performed. After 10 minutes of operation, microinjection of salusin 伪 into unilateral NTS of rats was performed to investigate the cardiovascular effect of salusin 伪 in NTS. The normal control group was injected with the same amount of artificial cerebrospinal fluid (ACSF). The results suggest that microinjection of salusin 伪 into bilateral or unilateral NTS can reduce blood pressure and heart rate in a dose-dependent manner. Microinjection of salusin 伪 into bilateral NTS does not affect arterial baroreflex. NTS preinjection of non-selective glutamate receptor antagonist KYN or bilateral vagotomy in anesthetized rats has no effect on lowering blood pressure and heart rate produced by salusin 伪. RVLM pretreatment with GABA agonist muscimol(10g L-1 could effectively block the effect of salusin 伪 on lowering blood pressure and slowing heart rate in NTS. In conclusion, the effects of salusin 伪 injection on blood pressure and heart rate may indirectly inhibit the excitability of anterior sympathetic neurons by stimulating the GABA receptor in RVLM.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R338

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