本文選題：壓力感受性反射敏感性 + ABR-DRs�。� 參考：《第二軍醫(yī)大學(xué)》2016年博士論文

【摘要】：動脈壓力感受性反射(arterial baroreflex,ABR)可以緩沖血壓的升高和降低,是心血管活動最重要的調(diào)節(jié)機(jī)制之一。ABR功能可以被量化,用壓力感受性反射敏感性(baroreflex sensitivity,BRS)表示。BRS被認(rèn)為是自主神經(jīng)系統(tǒng)的標(biāo)志。多中心臨床試驗(yàn)結(jié)果表明,無論有無心血管疾病,BRS都是高血壓、腦卒中、心律失常、心力衰竭及心肌梗死等疾病死亡率的強(qiáng)預(yù)測因子。當(dāng)前常用去竇弓神經(jīng)術(shù)破壞ABR傳入神經(jīng)(竇神經(jīng)和主動脈神經(jīng))作為ABR功能缺陷的動物模型。以該動物模型為基礎(chǔ),在ABR功能和心血管疾病的關(guān)系及ABR功能低下導(dǎo)致高血壓終末器官損傷等發(fā)面取得了一定的研究進(jìn)展。但是該模型的缺點(diǎn)是非自發(fā)性,不能真正地模擬ABR功能缺陷的原因,與臨床實(shí)際相差較大,并不是理想的動物模型。ABR缺陷的具體原因及分子機(jī)制現(xiàn)在還不明確,這也導(dǎo)致反射功能低下的基礎(chǔ)研究進(jìn)展緩慢。缺乏自發(fā)性ABR缺陷的動物模型是這一問題的限制因素。我們推測培育成功的自發(fā)性ABR缺陷動物,也會在許多心血管疾病方面表現(xiàn)出高風(fēng)險(xiǎn)性。基于這一模型,可以進(jìn)一步明確ABR缺陷的中樞分子靶標(biāo)。我們利用55只雄性和61只雌性SD大鼠篩選ABR功能正常和低下的大鼠。清醒自由活動狀態(tài)下BRS和血壓的測量結(jié)果顯示,雄性大鼠的平均BRS和收縮壓(systolic blood pressure,SBP)分別為0.77 ms/mm Hg和130 mm Hg。雌雄之間沒有差異。根據(jù)BRS的分布,我們將BRS0.6 ms/mm Hg的大鼠定義為動脈壓力感受性反射功能缺陷的大鼠(arterial baroreflex-deficient rats,ABR-DRs),將BRS0.8ms/mm Hg的大鼠定義為動脈壓力感受性反射功能正常的大鼠(arterial baroreflex-normal rats,ABR-NRs)。由于高血壓會影響B(tài)RS和交感活化,在培育過程中我們只選擇血壓正常的大鼠進(jìn)行培育和繁殖。根據(jù)上述標(biāo)準(zhǔn),我們選擇了20只(♂:♀=1:1)BRS低的大鼠作為ABR-DRs的原代,20只(♂:♀=1:1)BRS高的大鼠作為ABR-NRs的原代。每一株大鼠原代,均采取隨機(jī)配對的方法進(jìn)行交配,得到第一代ABR-DRs,及其對照ABR-NRs。隨后代數(shù)的大鼠采取“先近親繁殖后篩選”的方式進(jìn)行培育,即先兄妹近親繁殖,待幼鼠離乳后,再對其父本進(jìn)行清醒動物血壓和BRS的測量。只有兩個指標(biāo)均符合上述篩選的標(biāo)準(zhǔn),其子代才予以保留;否則,子代被淘汰。我們只篩選鑒定雄性動物,以減輕工作負(fù)擔(dān)。經(jīng)過20代的選擇性培育,兩株動物BRS差異顯著(ABR-NRs vs ABR-DRs,1.20±0.26 ms/mm Hg vs 0.46±0.12 ms/mm Hg,P0.01)。在培育過程中,盡管所有高血壓大鼠的子代均已被淘汰,ABR-DRs的血壓依然高于ABR-NRs。從第9代起,ABR-DRs的SBP和DBP比ABR-NRs均高約10 mm Hg。除了個別代數(shù),兩株大鼠的心率(heart rate,HR)并不存在差異。同時,我們對第19、20代的雌性大鼠也進(jìn)行了血壓和BRS的測量,發(fā)現(xiàn)雌雄間各個指標(biāo)趨勢相同。因此,在隨后的研究中,我們只選用雄性大鼠。我們在不同年齡段(1、2、4、6、8月齡)測量了兩株模型動物的BRS,以檢查年齡是否影響兩株大鼠間的差異。結(jié)果發(fā)現(xiàn),從1月齡起,ABR-DRs的BRS就顯著低于ABR-NRs(0.25±0.08 ms/mm Hg vs 0.72±0.25 ms/mm Hg,n=7,P0.01)。隨著月齡的增加,兩株大鼠的BRS總體均呈增加趨勢。到8月齡時,ABR-NRs的BRS高達(dá)1.19 ms/mm Hg,ABR-DRs則只增加到0.45 ms/mm Hg(P0.01)。在接下來的研究中,我們開始驗(yàn)證我們的工作假設(shè):心血管疾病的風(fēng)險(xiǎn)性隨著BRS的分離而明顯不同。我們通過股動、靜脈插管的方法動態(tài)監(jiān)測了不同月齡(1、2、4、6、8月齡)兩株大鼠的SBP、DBP和心率。結(jié)果發(fā)現(xiàn),在1月齡時,ABR-DRs的SBP和DBP就都顯著高于ABR-NRs約10 mm Hg,心率顯著快于ABR-NRs;隨著月齡的增加,兩株大鼠的血壓持續(xù)性緩慢增加,差異依然存在,但心率不再有差異。我們也用尾動脈測壓的方法動態(tài)監(jiān)測了不同月齡時的上述指標(biāo),得到了相似的結(jié)果。更為重要的是,ABR-DRs的高血壓發(fā)生率顯著高于ABR-NRs。在第10代時,ABR-NRs的高血壓發(fā)生率為10.7%(n=28),而ABR-DRs則為38.9%(n=36,P0.05)。在第19代,差異更為顯著(ABR-NRs,0%,n=28;ABR-DRs,57.8%,n=38;P0.01)。這些結(jié)果表明ABR-DRs的高血壓風(fēng)險(xiǎn)性增加。在2月齡時,我們檢測了兩株模型大鼠血清中血糖、血脂、肝腎功能相關(guān)代謝指標(biāo),發(fā)現(xiàn)ABR-DRs的隨機(jī)血糖、空腹血糖、膽固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白和瘦素均顯著高于ABR-NRs,表明ABR-DRs出現(xiàn)了血糖、血脂代謝異常。而空腹胰島素及肝腎功能相關(guān)指標(biāo)沒有差異。我們還檢測了8月齡大鼠的糖代謝相關(guān)指標(biāo)。與ABR-NRs相比,ABR-DRs的隨機(jī)血糖、空腹血糖和糖化血紅蛋白顯著升高。但是,二者的空腹胰島素水平并沒有顯著的差異。同時,ABR-DRs的糖耐量和胰島素耐量受損,但胰島素的分泌沒有問題,很可能是機(jī)體對胰島素產(chǎn)生了抵抗。因此,ABR-DRs存在代謝異常。我們觀察記錄了第20代ABR-NRs和ABR-DRs在1-25月齡期間的體重和進(jìn)食量。在1月齡和2月齡時,ABR-DRs的進(jìn)食量顯著高于ABR-NRs,但二者體重沒有差異。隨后在3-8月齡(6月齡除外)期間,兩株大鼠的進(jìn)食量相同;從9月齡開始,ABR-DRs的進(jìn)食量顯著低于ABR-NRs。從7月齡開始,ABR-DRs的體重持續(xù)顯著高于ABR-NRs。這兩個指標(biāo)的差異一直持續(xù)到24月齡。在10月齡時,我們對兩株大鼠進(jìn)行了脂肪分布的測量。與ABR-NRs相比,ABR-DRs的體重增加了96 g,總脂肪重量增加約45 g,其皮下、附睪、腸系膜、腎周及腹膜后、肩胛骨、胃周和主動脈周圍的脂肪重量和比例均顯著增加。這些結(jié)果表明,ABR-DRs存在超重問題。與ABR-NRs相比,ABR-DRs在舒張期和收縮期的左心室內(nèi)徑、左心室體積及射血體積、射血分?jǐn)?shù)、心輸出量均沒有顯著性差異,表明其并不存在心功能受損;但它們在舒張期和收縮期的左心室前壁厚度、收縮期的左心室后壁厚度顯著增加,這表明ABR-DRs存在心肌肥厚。通過稱重,我們發(fā)現(xiàn),與ABR-NRs相比,ABR-DRs的心臟、左心室和右心室的重量顯著增加,進(jìn)一步說明其存在心肌肥厚;ABR-DRs單位厘米的主動脈重量也顯著增加;二者右腎的重量并沒有統(tǒng)計(jì)學(xué)差異。2月齡大鼠的急性心肌缺血結(jié)果顯示,ABR-DRs左心室缺血組織重量和面積增加,說明其缺血損傷加重。在阻斷大腦中動脈造成缺血性腦卒中模型中,ABR-DRs的缺血面積和比例顯著增加,神經(jīng)缺陷評分也明顯增加。這些結(jié)果表明ABR-DRs急性心肌梗死和腦缺血的損傷加重。1-16月齡時的負(fù)重強(qiáng)迫游泳結(jié)果顯示,ABR-DRs在各個時間點(diǎn)的游泳時間均短于ABR-NRs;并且隨著年齡的增加,兩株大鼠的游泳時間逐漸降低。跑臺實(shí)驗(yàn)的結(jié)果也顯示ABR-DRs跑步至力竭的時間顯著短于ABR-NRs。這些結(jié)果說明,ABR-DRs的有氧運(yùn)動能力低下。我們也記錄了ABR-NRs和ABR-DRs的生存時間,結(jié)果發(fā)現(xiàn),ABR-DRs的壽命顯著縮短。以該動物模型為基礎(chǔ),我們展開了ABR功能缺陷的機(jī)制研究。我們通過記錄腎交感神經(jīng)活動(renal sympathetic nerve activity,RSNA)來檢測ABR-DRs的交感神經(jīng)是否存在過度活化�；A(chǔ)狀態(tài)下,ABR-DRs的RSNA與ABR-NRs并沒有統(tǒng)計(jì)學(xué)差異。然后,我們通過靜脈給予一定量的去氧腎上腺素來升高血壓(約50 mm Hg),激活壓力反射,以觀察ABR對交感神經(jīng)活化的調(diào)控。結(jié)果表明,ABR-DRs的RSNA變化率與ABR-NRs相比并沒有統(tǒng)計(jì)學(xué)差異。這些結(jié)果表明ABR-DRs壓力反射的交感支并沒有異常。與ABR-NRs相比,升壓后ABR-DRs的心率降低幅度顯著減小。而心率主要是由迷走神經(jīng)系統(tǒng)調(diào)控的,因此上述結(jié)果表明ABR-DRs的副交感功能受損。迷走神經(jīng)的中樞是疑核。疑核節(jié)前心迷走神經(jīng)元(cardiac vagal preganglionic neurons,CVPNs)決定了心臟的緊張性和反射性調(diào)控,其自發(fā)性電活動的強(qiáng)弱與疑核副交感功能密切相關(guān)。我們利用逆向熒光染料(XRITC,Invitrogen)標(biāo)記CVPNs,然后進(jìn)行電生理膜片鉗實(shí)驗(yàn)。與ABR-NRs相比,ABR-DRs疑核CVPNs的自發(fā)性放電頻率頻率顯著降低。加入外源性谷氨酸,可興奮CVPNs,增加自發(fā)性放電的頻率,但ABR-DRs增加的百分比顯著降低。這些數(shù)據(jù)表明,ABR-DRs的疑核CVPNs的電活動異常。谷氨酸能和γ-氨基丁酸能突觸傳遞通路是疑核CVPNs的主要突觸傳入。我們同時阻斷NMDA(N-methyl-D-aspartic acid,N-甲基-D-天冬氨酸)受體、AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid,α-氨基-3-羥基-5-甲基-4-異惡唑丙酸)受體和GABAA(γ-aminobutyric acid,γ-氨基丁酸)受體,ABR-NRs和ABR-DRs CVPNs自發(fā)性放電的差異被取消。但是單獨(dú)阻斷GABAA受體并不影響兩組大鼠CVPNs自發(fā)性放電之間的差異。因此,ABR-DRs疑核CVPNs的自發(fā)性放電頻率降低主要是由谷氨酸能突觸通路影響的。AMPA受體阻斷劑預(yù)處理可以取消兩株模型大鼠CVPNs自發(fā)性放電頻率的差異,并且完全取消了谷氨酸對CVPNs的興奮作用。NMDA阻斷劑并不能取消兩株大鼠間的放電差異,也不影響谷氨酸對CVPNs的興奮作用,并且ABR-DRs放電頻率增加的百分比依然顯著低于ABR-NRs。因此,AMPA受體參與了ABR-DRs疑核CVPNs的電活動異常。本課題的實(shí)驗(yàn)結(jié)果表明,心血管疾病的危險(xiǎn)因素確實(shí)隨著BRS的分離而明顯不同。ABR-DRs在許多心血管疾病方面表現(xiàn)出高風(fēng)險(xiǎn)性,如高血壓、高血糖、高血脂、超重及有氧運(yùn)動能力低下。BRS受損導(dǎo)致迷走神經(jīng)傳出減弱,是心血管疾病的危險(xiǎn)因素,也會顯著縮短生存時間。疑核心迷走神經(jīng)元自發(fā)性放電頻率降低,對谷氨酸反應(yīng)減弱,AMPA受體很可能參與了ABR功能受損。
[Abstract]:Arterial baroreflex (ABR) can cushion the increase and decrease of blood pressure. It is one of the most important regulatory mechanisms of cardiovascular activity..ABR function can be quantified. With the baroreflex sensitivity (BRS) sensitivity (baroreflex sensitivity, BRS),.BRS is considered as a sign of the autonomic nervous system. A multicenter clinical trial junction The results show that BRS is a strong predictor of the mortality of hypertension, stroke, arrhythmia, heart failure, and myocardial infarction, regardless of the cardiovascular disease. The current use of DDN to destroy the ABR afferent nerve (sinus nerve and aortic nerve) as an animal model of ABR dysfunction. Based on this animal model, ABR work The relationship with cardiovascular disease and the hypofunction of ABR lead to the development of the end organ damage of hypertension. However, the defect of the model is non spontaneous and can not truly simulate the causes of ABR functional defects, which are different from the clinical practice, and are not the specific causes and molecules of the.ABR defect in the animal model. The mechanism is not yet clear, which has also led to a slow progress in basic research on reflex hypofunction. The animal model lacking spontaneous ABR defects is a limiting factor in this problem. We speculate that a successful spontaneous ABR deficient animal may also be highly risky in many cardiovascular diseases. Based on this model, it can be further developed. The central molecular target of ABR defect was identified. We used 55 male and 61 female SD rats to screen the normal and low function rats of ABR. The results of BRS and blood pressure in conscious free activity showed that the average BRS and systolic blood pressure (systolic blood pressure, SBP) in male rats were 0.77 ms/mm Hg and 130 mm. According to the distribution of BRS, we defined the rats of BRS0.6 ms/mm Hg as the rat (arterial baroreflex-deficient rats, ABR-DRs) of the arterial baroreceptor reflex (arterial baroreflex-deficient rats, ABR-DRs), and defined the rats of BRS0.8ms/mm Hg as a rat with normal arterial baroreceptor reflex (arterial baroreflex-normal). Blood pressure affects BRS and sympathetic activation. In the process of breeding, we only choose rats with normal blood pressure to breed and reproduce. According to the above criteria, we chose 20 rats with low BRS as the original ABR-DRs, and 20 rats with high BRS as the original generation of ABR-NRs. In the method of mating, the first generation ABR-DRs was obtained, and the rats of the ABR-NRs. subsequent algebra were bred by "first close breeding after screening". That is, the siblings were inbred, and then the young rats were separated from the milk, and then the blood pressure and BRS of the waking animals were measured. Only two indexes were in line with the criteria of the above screening. Instead, the progeny was eliminated. We only screened the male animals to reduce the burden of work. After 20 generations of selective breeding, two animals had significant differences in BRS (ABR-NRs vs ABR-DRs, 1.20 + 0.26 ms/mm Hg vs 0.46 + 0.12 ms/mm Hg, P0.01). In the breeding process, all the offspring of the hypertensive rats were eliminated, ABR The blood pressure of -DRs was still higher than that of ABR-NRs. from the ninth generation. The SBP and DBP of ABR-DRs were 10 mm Hg. higher than that of ABR-NRs. The heart rate (heart rate, HR) of two rats did not differ. In the later study, we only chose male rats. We measured the BRS of two model animals at different age groups (1,2,4,6,8 months of age) to check whether the age affected the difference between two rats. The results showed that from 1 month old, the BRS of ABR-DRs was significantly lower than ABR-NRs (0.25 + 0.08 ms/mm Hg vs 0.72 + 0.25 ms/mm Hg, n=7, P0.01). As the age increased, the BRS of the two rats tended to increase. At 8 month old, the BRS of ABR-NRs was 1.19 ms/mm Hg, and ABR-DRs only increased to 0.45 ms/mm Hg (P0.01). In the next study, we began to verify our work hypothesis that the risk of cardiovascular disease was significantly different with the separation of BRS. The method of intubation dynamically monitored the SBP, DBP and heart rate of two rats of different months of age (1,2,4,6,8 months of age). The results showed that the SBP and DBP of ABR-DRs were significantly higher than that of ABR-NRs about 10 mm Hg at 1 month old, and the heart rate was significantly faster than ABR-NRs. With the increase of month age, the blood pressure of two rats increased slowly, but the difference still existed, but heart rate was no longer There was a difference. We also used the tail artery pressure measurement to dynamically monitor the above indicators at different months of age and get similar results. More importantly, the incidence of hypertension in ABR-DRs was significantly higher than that of ABR-NRs. at the tenth generation. The incidence of hypertension in ABR-NRs was 10.7% (n=28), while ABR-DRs was 38.9% (n=36, P0.05). In the nineteenth generation, the difference was more significant. The results were significant (ABR-NRs, 0%, n=28; ABR-DRs, 57.8%, n=38; P0.01). These results showed an increase in the risk of hypertension in ABR-DRs. At 2 month old, we detected blood glucose, blood lipid, liver and kidney function related metabolic indicators in two model rats, and found the random blood sugar, fasting blood glucose, cholesterol, triglyceride, LDL, high density of ABR-DRs. Both lipoprotein and leptin were significantly higher than ABR-NRs, indicating that ABR-DRs had blood glucose and abnormal metabolism of blood lipids. There was no difference in fasting insulin and liver and kidney function related indexes. We also detected the glucose metabolism related indexes in 8 month old rats. Compared with ABR-NRs, the random blood sugar, empty abdomen blood glucose and glycated hemoglobin were significantly higher than that of ABR-NRs. But, two There was no significant difference in the level of fasting insulin. At the same time, ABR-DRs's glucose tolerance and insulin tolerance were impaired, but insulin secretion was not a problem. It was probably the body's resistance to insulin. Therefore, there was a metabolic abnormality in ABR-DRs. We observed the weight and eating of the twentieth generation of ABR-NRs and ABR-DRs during the period of 1-25 months of age. At 1 month old and 2 month old, the intake of ABR-DRs was significantly higher than that of ABR-NRs, but there was no difference in weight between the two and the 3-8 months of age (except for 6 month old), and the intake of the two rats was the same; from 9 month old, the intake of ABR-DRs was significantly lower than that of ABR-NRs. from 7 month old, and the weight of ABR-DRs was significantly higher than that of ABR-NRs., the two indicators. The difference continued to 24 month old. At 10 month old, we measured the fat distribution in two rats. Compared with ABR-NRs, the weight of ABR-DRs increased by 96 g and the total fat weight increased by about 45 g. The weight and proportion of fat around the stomach and around the stomach and aorta increased significantly in the subcutaneous, epididymis, mesentery, perirenal and retroperitoneal, scapula, and the aorta. The results showed that ABR-DRs was overweight. Compared with ABR-NRs, ABR-DRs had no significant difference in the diastolic and systolic left ventricular diameter, left ventricular volume, ejection volume, ejection fraction, and cardiac output, indicating that there was no impairment of cardiac function, but they were in systolic and systolic left ventricular anterior wall thickness and left systolic left The thickness of the posterior wall of the ventricle increased significantly, which indicates that ABR-DRs has cardiac hypertrophy. By weighing, we found that the weight of the heart, the left ventricle and the right ventricle of the ABR-DRs increased significantly compared with ABR-NRs, further indicating the existence of cardiac hypertrophy; the weight of the aorta in ABR-DRs centimeters was also significantly increased; and the weight of the right kidney was not statistically significant in two. The results of acute myocardial ischemia in.2 month old rats showed an increase in the weight and area of ABR-DRs left ventricular ischemic tissue, indicating that the ischemic injury was aggravated. The ischemic area and proportion of ABR-DRs increased significantly in the occlusion of the middle cerebral artery, and the neurological deficit score increased significantly. These results showed that the ABR-DRs was acute. The results showed that the swimming time of ABR-DRs at all time points was shorter than that of ABR-NRs when the injury of myocardial infarction and cerebral ischemia aggravated the.1-16 months of age, and the swimming time of two rats decreased gradually with the increase of age. The result of the runway experiment also showed that the time of ABR-DRs running to exhaustion was significantly shorter than that of ABR-NRs.. The results showed that the aerobic activity of ABR-DRs was low. We also recorded the survival time of ABR-NRs and ABR-DRs, and found that the life span of ABR-DRs was significantly shortened. Based on the animal model, we developed the mechanism of the ABR function defect. We checked the renal sympathetic activity (renal sympathetic nerve activity, RSNA). There was no significant activation in the sympathetic nerve of ABR-DRs. In the base state, there was no statistical difference between the RSNA of ABR-DRs and ABR-NRs. Then, we administered a certain amount of deoxyadrenaline to elevate hypertension (about 50 mm Hg) to activate the pressure reflex to observe the regulation of the sympathetic activation of ABR. The results showed that the RSNA change of ABR-DRs. There was no statistical difference compared with ABR-NRs. These results showed that the sympathetic branches of the ABR-DRs pressure reflex were not abnormal. Compared with ABR-NRs, the heart rate decreased significantly after the boost, and the heart rate was mainly regulated by the vagus system. Therefore, the above results indicate that the parasympathetic function of ABR-DRs is impaired. The vagus nerve is impaired. The center is the nucleus. Cardiac vagal preganglionic neurons (CVPNs) determines the tension and reflex regulation of the heart. The intensity of spontaneous electrical activity is closely related to the parasympathetic parasympathetic function. We use the reverse fluorescent dye (XRITC, Invitrogen) to mark CVPNs and then carry out the electrophysiological patch clamp experiment. Compared with ABR-NRs, the spontaneous discharge frequency of ABR-DRs CVPNs was significantly reduced. Adding exogenous glutamic acid could excite CVPNs and increase the frequency of spontaneous discharge, but the percentage of ABR-DRs increased significantly. These data indicate that the electrical activity of ABR-DRs in the nuclear CVPNs is abnormal. Glutamate and gamma aminobutyric acid can transfer through the synapse. The pathway is the main synapse afferent of the nuclear CVPNs. We also block the NMDA (N-methyl-D-aspartic acid, N- methyl -D- aspartic acid) receptor, AMPA (alpha -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, alpha amino -3- hydroxyl -5- methyl -4- isooxazole propionic acid) receptor and the receptor of gamma aminobutyric acid (gamma aminobutyric acid) The difference between the spontaneous discharge of s CVPNs was cancelled. But the isolation of GABAA receptor alone did not affect the difference between the spontaneous discharge of the two groups of rats. Therefore, the spontaneous discharge frequency of CVPNs in the ABR-DRs nuclear CVPNs was mainly caused by the preconditioning of the.AMPA receptor blocker, which was influenced by the glutamic acid synaptic pathway, and the CVPNs self of the two model rats could be cancelled. The difference in the frequency of hair discharge, and completely abolished the excitatory effect of glutamic acid on CVPNs,.NMDA blocker did not cancel the discharge difference between two rats, and did not affect the excitatory effect of glutamic acid on CVPNs, and the percentage of the ABR-DRs discharge frequency increased significantly lower than that of ABR-NRs., so the AMPA receptor was involved in ABR-DRs suspected CVPNs. The results of this study showed that the risk factors of cardiovascular disease did differ significantly with the separation of BRS and.ABR-DRs showed high risk in many cardiovascular diseases, such as hypertension, hyperglycemia, hyperlipidemia, overweight and impaired aerobic activity.BRS, which resulted in the weakening of the vagus nerve, which was the cardiovascular disease. The risk factors of the disease also significantly shorten the survival time. The spontaneous discharge frequency of the nucleus vagus neurons is reduced, the response to glutamic acid is weakened, and the AMPA receptor is likely to be involved in the impairment of ABR function.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R-332;R54

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