本文選題：血管緊張素Ⅱ + 小電導(dǎo)鈣激活鉀通道��； 參考：《西南醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:心房顫動(Atrial fibrillation,AF)是臨床最常見的心律失常之一,明顯增加患者的死亡率及致殘率,是一種與年齡密切相關(guān)的漸進性疾病,并可使?jié)撛诘男呐K疾病惡化。AF的發(fā)病機制迄今為止不明,已經(jīng)提出了許多假說,從AF局灶起源假說到多發(fā)子波折返假說再到局灶驅(qū)動伴顫動樣傳導(dǎo)、肺靜脈觸發(fā)起源假說,但沒有一種學(xué)說能解釋AF所有的現(xiàn)象[1-3]。盡管觸發(fā)和折返作為AF的發(fā)生機制逐漸被接受,但AF的維持基質(zhì)仍有許多尚未闡明的問題。新近發(fā)現(xiàn)的SK2通道為小電導(dǎo)鈣激活鉀通道(Small conductance Ca2+-activated K+channel,SK通道)的一個亞型,因具有心房選擇性并且通道的改變與AF發(fā)生有關(guān),成為近年大家研究的熱點之一。該通道對鉀離子具有選擇性,對電壓不敏感而對Ca2+高度敏感。業(yè)已證實AF的電重構(gòu)涉及細胞內(nèi)Ca2+超載,循環(huán)或組織血管緊張素Ⅱ(Angiotensin Ⅱ,AngⅡ)的增加可使細胞內(nèi)鈣進一步增多導(dǎo)致AF加重[4]。而SK2通道對細胞內(nèi)鈣高度敏感,因此我們推測AngⅡ?qū)е翧F加重可能涉及了對SK2通道的調(diào)控,然而通過文獻的復(fù)習(xí)未見相關(guān)報道。因此本研究的目的是探討AngⅡ?qū)K2通道的調(diào)控在AF發(fā)生中的作用機制。方法:健康成年比格犬25只隨機分為5組(每組5只):分別為假手術(shù)組(Sham組)、起搏組(Pacing組)、起搏+血管緊張素Ⅱ組(Pacing+AngⅡ組)、起搏+纈沙坦組(Pacing+Valsartan組)、起搏+血管緊張素Ⅱ+纈沙坦組(Pacing+AngⅡ+Valsartan組)。實驗各組用藥前及用藥后常規(guī)測量血壓,每次測量3次取平均值。其中加藥組于起搏前2周分別給予AngⅡ 110ng/kg/min皮下持續(xù)微量泵入或(和)Valsartan 30mg/kg/d口服。給藥后所有犬經(jīng)戊巴比妥鈉麻醉后常規(guī)氣管插管機械輔助通氣,檢測心電圖變化,經(jīng)右側(cè)股靜脈插入起搏電極至右心房,電極近端連接電生理起搏系統(tǒng),除Sham組外其余各組均給予快速心房起搏(頻率600次/分)8小時,起搏前及起搏后每小時測量心房有效不應(yīng)期(atrialeffectiverefractoryperiod,aerp)和af發(fā)生頻率及持續(xù)時間。起搏結(jié)束后抽取動物靜脈血離心,檢測血清angii濃度變化,開胸取左右心房組織檢測組織angii濃度變化,westernblotting方法檢測各組右心房組織sk2通道蛋白表達的變化。結(jié)果:1.血壓的變化:angii預(yù)處理2周后,pacing+angii組血壓上升45±3.53mmhg與sham組比較,差異明顯(p0.01);其余各組與sham組比較差異無統(tǒng)計學(xué)意義(p0.05)。2.起搏后aerp的變化:與sham組比較,pacing組、pacing+angii組、pacing+angii+valsartan組aerp明顯縮短(p0.01),pacing+angii組縮短最為顯著,pacing+valsartan組無明顯縮短(p0.05);與pacing組比較,pacing+angii組aerp縮短(p0.01),pacing+valsartan組、pacing+angii+valsartan組aerp延長(p0.01)。3.起搏后血清及左右心房組織angii濃度變化:與sham組比較,pacing組血清和ra組織angii濃度明顯升高(p0.01),la組織angii濃度也升高(p0.05),pacing+valsartan組血清及左右心房組織angii濃度雖有所升高,但差異無統(tǒng)計學(xué)意義(p0.05)。4.各組burst刺激誘發(fā)af的頻率和時間變化:與sham組比較,pacing組、pacing+angii組誘發(fā)af的頻率和時間明顯增加(p0.01),pacing+valsartan組無明顯差異(p0.05);與pacing組比較,pacing+angii組誘發(fā)af的頻率和時間增多(p0.01),而pacing+valsartan組、pacing+angii+valsartan組明顯減少(p0.01)。5.westernblotting檢測sk2通道蛋白相對表達量結(jié)果顯示:與sham組比較,pacing組、pacing+angii組、pacing+angii+valsartan組蛋白表達明顯下降(p0.01),其中pacing+angii組下降最為顯著,pacing+valsartan組也有下降,但明顯沒有其余各組下降明顯(p0.05);與pacing組比較,pacing+angii組蛋白表達下降(p0.01),pacing+valsartan組增多(p0.01),pacing+angii+valsartan組也有所上調(diào)(p0.05)。結(jié)論:1.快速起搏可導(dǎo)致心房發(fā)生電重構(gòu),其中AngⅡ可加重心房的電重構(gòu),而Valsartan可減輕心房的電重構(gòu)減少AF的發(fā)生。2.快速起搏可導(dǎo)致血清及左右心房組織AngⅡ濃度增加,這是易于AF發(fā)生和維持的可能原因之一。3.SK2通道可能參與了心房的電重構(gòu)過程,快速起搏可導(dǎo)致心肌組織SK2通道蛋白表達的下調(diào),AngⅡ進一步下調(diào)SK2通道蛋白的表達,這可能是導(dǎo)致AF加重的原因之一。
[Abstract]:Objective: Atrial fibrillation (AF) is one of the most common arrhythmias in the clinic. It obviously increases the mortality and disability rate of the patients. It is a progressive disease closely related to age, and it can make the pathogenesis of the potential heart disease worse than that of.AF so far. Many hypotheses have been put forward, from the hypothesis of AF focal origin hypothesis. However, there is no one theory that can explain all AF phenomenon [1-3]., although triggering and reentry are gradually accepted as the mechanism of AF, but there are still many problems that have not been clarified in the AF maintenance matrix. The newly discovered SK2 channel is small conductance calcium. A subtype that activates the potassium channel (Small conductance Ca2+-activated K+channel, SK channel) has become one of the hotspots of recent research because of its atrial selectivity and changes in channels with AF. This channel is selective to potassium ions and is highly sensitive to voltage and is highly sensitive to Ca2+. It has been proved that the electrical reconfiguration of AF is involved. In cell Ca2+ overload, the increase of circulating or tissue angiotensin II (Angiotensin II, Ang II) increases the increase of intracellular calcium and causes AF to aggravate [4]. and SK2 channel is highly sensitive to intracellular calcium. Therefore, we speculate that Ang II leads to AF aggravation and may involve the regulation of SK2 channel. However, no related reports have been reported in literature review. Therefore, the purpose of this study is to explore the mechanism of Ang II regulation of the SK2 channel in the occurrence of AF. Methods: 25 healthy adult beagles were randomly divided into 5 groups (group Sham), pacing group (group Pacing), pacing + angiotensin II Group (group Pacing+Ang II), pacing + valsartan group (group Pacing+Valsartan), pacing +, and pacing + Angiotensin II + valsartan group (group Pacing+Ang II +Valsartan). The average blood pressure was measured 3 times before and after medication. The group was given Ang II 110ng/kg/min subcutaneous micropump or (and) Valsartan 30mg/kg/d orally at 2 weeks before pacing. All dogs were given pentobarbital sodium after administration. After anesthesia, the routine endotracheal intubation mechanical ventilation was used to detect the changes of electrocardiogram. The pacing electrode was inserted into the right atrium through the right femoral vein, and the electrophysiological pacing system was connected to the proximal end of the electrode. The other groups were given fast atrial pacing (frequency 600 / min) for 8 hours except the Sham group, and the atrial effective refractory period was measured every hour before and after pacing (atrial The frequency and duration of effectiverefractoryperiod, AERP) and AF. After the end of the pacing, the animal vein blood centrifugation was extracted, the serum AngII concentration was detected, the concentration of AngII in the left and right atrium tissue was detected by open chest, and the westernblotting method was used to detect the changes of SK2 channel protein expression in the right atrium tissue. Results: 1. the change of blood pressure: a After 2 weeks of ngii preconditioning, the blood pressure increased by 45 + 3.53mmhg in group pacing+angii compared with that in group sham, the difference was significant (P0.01). There was no significant difference between the other groups and sham group (P0.05) after.2. pacing. Compared with group pacing, AERP shortened (P0.01), pacing+valsartan group, and pacing+angii+valsartan group AERP lengthening (P0.01).3. pacing. Compared with group pacing, the concentration of serum and left and right atrial tissue in pacing+angii group was significantly higher than that in group pacing. The concentration of tissue AngII increased (P0.05), while the AngII concentration in serum and left and right atrium tissues in group pacing+valsartan increased, but there was no significant difference in the frequency and time of AF in.4. groups (P0.05). Compared with the sham group, the frequency and time of AF in pacing group and pacing+angii group increased significantly. There was no significant difference in the group (P0.05). Compared with the pacing group, the frequency and time of inducing AF increased in group pacing+angii (P0.01), but in group pacing+valsartan, pacing+angii+valsartan group decreased significantly (P0.01).5.westernblotting detection SK2 channel protein relative expression. The expression of histone decreased significantly (P0.01), in which the pacing+angii group decreased most significantly and the pacing+valsartan group decreased, but no other groups were obviously decreased (P0.05). Compared with the pacing group, the protein expression in the pacing+angii group decreased (P0.01), the pacing+valsartan group increased (P0.01), and the pacing+angii+valsartan group was also up (P0.05). 1. rapid pacing can lead to atrial electrical remodeling, in which Ang II can aggravate the electrical remodeling of the atrium, and Valsartan can reduce the electrical remodeling of the atrium and reduce the occurrence of AF,.2. rapid pacing can lead to the increase of the concentration of Ang II in the serum and the left and right atrium, which is one of the possible causes of the occurrence and maintenance of AF, and the.3.SK2 channel may be involved in the atrium. The rapid pacing can lead to the downregulation of SK2 channel protein expression in myocardial tissue, and Ang II further downregulation the expression of SK2 channel protein, which may be one of the reasons for the aggravation of AF.
【學(xué)位授予單位】：西南醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R541.75

【參考文獻】

相關(guān)期刊論文 前10條

1 吳鵬;劉星;范忠才;;鈣離子調(diào)節(jié)異常對心房顫動影響的研究進展[J];西南國防醫(yī)藥;2015年01期

2 楊錦龍;范忠才;;轉(zhuǎn)化生長因子β1與心肌纖維化的研究進展[J];醫(yī)學(xué)理論與實踐;2014年08期

3 吳智明;石開虎;吳君旭;徐盛松;陶輝;宣海洋;曹煒;沙紀名;占紅英;;風(fēng)濕性心臟瓣膜病合并心房顫動患者中SK2與CX40蛋白的表達變化及相關(guān)性[J];安徽醫(yī)科大學(xué)學(xué)報;2014年04期

4 李濤;毛亮;譚曉秋;李妙齡;楊艷;劉智飛;曾曉榮;;ELISA方法檢測慢性心房顫動患者心房肌中SK2蛋白的表達[J];重慶醫(yī)學(xué);2012年08期

5 龍毅;王嬌;周亞南;修蕓;殷躍輝;;血管緊張素Ⅱ及替米沙坦對大鼠心房肌細胞鉀和鈣電流的影響[J];第三軍醫(yī)大學(xué)學(xué)報;2011年12期

6 李妙齡;李濤;雷明;譚曉秋;楊艷;劉泰i，

本文編號：2073935