本文選題：醛固酮 + TASK通道�。� 參考：《河北醫(yī)科大學》2017年碩士論文

【摘要】：高血壓是一種常見的慢性非傳染性疾病,是誘發(fā)心腦血管疾病最危險的因素之一。原發(fā)性醛固酮增多癥(Primary aldosteronism,PA)是由腎上腺皮質分泌過多的醛固酮,導致血容量增加,潴鈉排鉀及代謝型堿中毒,臨床表現(xiàn)為高血壓和低血鉀的一組異質性疾病。PA是繼發(fā)性高血壓的常見原因之一,約占高血壓人群的10%,占難治性高血壓的20%。然而,目前高醛固酮血癥導致血壓升高的機制仍然存在爭議。以前涉及醛固酮信號系統(tǒng)如何參與高血壓的發(fā)生發(fā)展的研究,主要是在正常大小鼠上短期給予醛固酮處理,或是在其他類型的高血壓動物模型上完成。這些研究結果能否真實地反映PA尤其是特發(fā)性醛固酮增多癥中高血壓的發(fā)病機理有待商榷。因此需要一個理想的PA動物模型,才能系統(tǒng)、全面、精準地研究PA高血壓的發(fā)病機制。研究發(fā)現(xiàn),TWIK-related acid-sensitive K(TASK)通道敲除小鼠(TASK-/-)表現(xiàn)為高醛固酮血癥、高血壓、低腎素,且鹽水負荷實驗或血管緊張素Ⅱ受體阻斷劑不能抑制醛固酮的過量分泌,這與人群中的特發(fā)性醛固酮增多癥非常相似。目前,TASK敲除小鼠已成為業(yè)界公認的模擬PA的動物模型。本課題應用此模型初步觀察了PA高血壓發(fā)生的神經(jīng)機制,為后續(xù)研究明確了方向。目的:本研究旨在應用無線遙測系統(tǒng)、無創(chuàng)體積描記系統(tǒng)和Western blot等技術手段,主要觀察TASK通道敲除/高醛固酮血癥對動脈壓力感受器反射的影響。方法:1應用無線遙測系統(tǒng)測量清醒狀態(tài)下TASK-/-小鼠和對照小鼠(TASK+/+)基礎血壓和心率的差異;觀察腹腔注射阿托品、普萘洛爾和溴化六甲銨對兩組小鼠血壓和心率的影響。2通過低氧和高碳酸刺激激活中樞和外周呼吸化學感受器,觀察兩組小鼠心血管活動的變化。3應用Western Blot方法,檢測兩組小鼠延髓腹外側區(qū)(RVLM)鹽皮質激素受體表達水平的異同。結果:1清醒狀態(tài)下TASK-/-小鼠收縮壓、舒張壓、平均動脈壓均顯著高于TASK+/+小鼠,但心率并沒有明顯差異。2不同濃度的CO2刺激對兩組小鼠動脈血壓無顯著性影響;低氧(10%O2)刺激使TASK-/-小鼠的平均動脈壓顯著下降,而TASK+/+小鼠血壓無顯著改變。3阿托品引起TASK-/-與TASK+/+小鼠的心率均增加,增幅無顯著差異,提示兩組小鼠副交感神經(jīng)緊張性相似。4普萘洛爾可減慢兩組小鼠的心率,但TASK-/-小鼠減慢更顯著,提示敲除組小鼠交感神經(jīng)緊張性增強。5溴化六甲銨降低兩組小鼠動脈血壓,但TASK-/-小鼠降低更明顯,提示交感縮血管神經(jīng)緊張性增強。6 Western Blot結果表明,TASK-/-小鼠RVLM的鹽皮質激素受體表達顯著升高。結論:TASK通道敲除引起動脈血壓升高,TASK-/-小鼠的高血壓可能與壓力感受器反射抑制、交感神經(jīng)緊張性增強有關,而造成后者的原因可能與RVLM鹽皮質激素受體的過表達有關。
[Abstract]:Hypertension is a common chronic non-communicable disease and one of the most dangerous factors inducing cardiovascular and cerebrovascular diseases. Primary aldosteronismPAA is a hyperaldosterone secreted by the adrenal cortex, resulting in increased blood volume, potassium excretion from the water storage and metabolic alkalosis. The clinical manifestations of hypertension and hypokalemia of a group of heterogeneous diseases. PA is one of the common causes of secondary hypertension, about 10% of the hypertensive population, accounting for 20% of refractory hypertension. However, the mechanism of hyperaldosteronemia leading to elevated blood pressure remains controversial. Previous studies on how aldosterone signaling systems are involved in the pathogenesis and development of hypertension have mainly been done in normal mice and mice treated with aldosterone for a short time or in other types of hypertensive animal models. Whether these findings can truly reflect the pathogenesis of hypertension in PA, especially idiopathic aldosteronism, is open to question. Therefore, an ideal PA animal model is needed to systematically and accurately study the pathogenesis of PA hypertension. It was found that TWIK-related acid-sensitive task channel knockout mice showed hyperaldosteronemia, hypertension, low renin, and saline loading test or angiotensin 鈪，

本文編號：1991776