本文選題：salusin + 大鼠��； 參考：《蘭州大學(xué)》2012年碩士論文

【摘要】：近年來研究資料表明,高血壓、動脈粥樣硬化等心血管疾病與心血管活性肽的作用呈高度的相關(guān)性。血管緊張素、內(nèi)皮素等一系列心血管活性肽的發(fā)現(xiàn),豐富了高血壓、動脈粥樣硬化等心血管疾病的研究理論,由此催生出一批新的臨床治療藥物,提高了高血壓、動脈粥樣硬化等心血管疾病的治療效果,改善了患者的生活質(zhì)量。 Salusins是從已經(jīng)完成的人類基因組計(jì)劃的基因文庫中,根據(jù)表達(dá)序列標(biāo)記的開放閱讀框架預(yù)測的肽類物質(zhì)中篩選的,主要存在于造血系統(tǒng)、內(nèi)分泌系統(tǒng)和中樞神經(jīng)系統(tǒng),是具有降低血壓和絲裂原樣效應(yīng)的生物活性肽。成熟的salusins由20個(gè)氨基酸組成的salusin α和28個(gè)氨基酸組成的salusin β兩種活性單體組成。salusin α廣泛分布于人和大鼠的骨髓、內(nèi)分泌腺和腦組織,具有降低血壓、減緩心率等生物學(xué)效應(yīng),可能參與高血壓、動脈粥樣硬化等心血管疾病的發(fā)生過程。腦室內(nèi)salusins對大鼠心血管活動產(chǎn)生的調(diào)節(jié)作用,已有文獻(xiàn)報(bào)道。延髓是心血管活動調(diào)節(jié)的基本中樞。孤束核(nucleus tractus solitarii, NTS)作為延髓的重要組成部分,在心血管活動調(diào)節(jié)過程中發(fā)揮著重要作用。salusin α在大鼠孤束核是否對心血管活動有調(diào)節(jié)作用及其機(jī)制研究尚不清楚。所以本研究主要探討孤束核內(nèi)salusin α的心血管效應(yīng)及其機(jī)制。 實(shí)驗(yàn)選用雄性SD大鼠,體重250～300g。實(shí)驗(yàn)分組為：1.雙側(cè)NTS給藥組：以人工腦脊液(aCSF)為對照,在大鼠雙側(cè)NTS分別微量注射不同劑量salusin α,觀察對血壓和心率的影響。2.單側(cè)NTS給藥組：在大鼠單側(cè)NTS分別微量注射不同劑量salusin α,觀察對血壓和心率的影響。3.動脈壓力感受性反射組：以aCSF為對照,雙側(cè)NTS微量注射salusin α,觀察對動脈壓力感受性反射功能的影響。4.機(jī)制組：預(yù)先分別在單側(cè)NTS注射非選擇性谷氨酸受體拮抗劑犬尿烯酸(kynurenic acid, KYN)、頭端延髓腹外側(cè)區(qū)(rostral ventrolateral medulla, RVLM)預(yù)先注射γ-氨基丁酸(gamma-aminobutyric acid, GABA)激動劑musciml、行雙側(cè)迷走神經(jīng)切除術(shù),10min后在大鼠單側(cè)NTS分別微量注射salusin α,探討NTS內(nèi)salusin α心血管效應(yīng)機(jī)制。各組的正常對照均為在相應(yīng)的部位注射同等量的人工腦脊液(aCSF)。 實(shí)驗(yàn)結(jié)果提示在NTS雙側(cè)或單側(cè)微量注射salusin α,可劑量依賴性的降低大鼠血壓,減緩心率。雙側(cè)NTS微量注射salusin α不影響麻醉大鼠的動脈壓力感受性反射。NTS預(yù)先注射非選擇性谷氨酸受體拮抗劑KYN或雙側(cè)迷走神經(jīng)切除均不影響salusin α產(chǎn)生的降低血壓和減緩心率效應(yīng)(P0.05)。RVLM預(yù)先注射γ-氨基丁酸(GABA)激動劑muscimol(10g·L-1)能有效阻斷salusin α在NTS內(nèi)產(chǎn)生的降低血壓和減緩心率效應(yīng)(P0.05)。 綜上所述,NTS注射salusin α產(chǎn)生的降低血壓、減緩心率的效應(yīng)可能間接通過激動RVLM內(nèi)GABA受體,抑制前交感神經(jīng)元興奮性發(fā)揮作用。
[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 偽 and 28 amino acids salusin 尾. Salusin 偽 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 偽 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 偽 to observe the effect of salusin 偽 on blood pressure and heart rate. Unilateral NTS group: rats were given microinjection of different doses of salusin 偽 into unilateral NTS to observe the effects on blood pressure and heart rate. Arterial baroreflex group: bilateral NTS was microinjected with salusin 偽 to observe the effect of salusin 偽 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 偽 into unilateral NTS of rats was performed to investigate the cardiovascular effect of salusin 偽 in NTS. The normal control group was injected with the same amount of artificial cerebrospinal fluid (ACSF). The results suggest that microinjection of salusin 偽 into bilateral or unilateral NTS can reduce blood pressure and heart rate in a dose-dependent manner. Microinjection of salusin 偽 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 偽. RVLM pretreatment with GABA agonist muscimol(10g L-1 could effectively block the effect of salusin 偽 on lowering blood pressure and slowing heart rate in NTS. In conclusion, the effects of salusin 偽 injection on blood pressure and heart rate may indirectly inhibit the excitability of anterior sympathetic neurons by stimulating the GABA receptor in RVLM.
【學(xué)位授予單位】：蘭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R338

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本文編號：1953114