【摘要】：研究背景糖尿病心肌病(Diabetic Cardiomyopathy,DC)最初由Rubler于1972年首先描述,定義為無(wú)冠狀動(dòng)脈疾病、高血壓或其他潛在病因的由糖尿病引起的一種特異性心肌病。常表現(xiàn)為心臟順應(yīng)性降低,舒張期充盈受阻或收縮功能不全。研究發(fā)現(xiàn)高血糖及相關(guān)的代謝紊亂可直接損傷心肌,從而導(dǎo)致DC,因此糖尿病心血管并發(fā)癥的患者均可合并DC。臨床上DC擁有很大的發(fā)病人群,對(duì)患者造成很大的危害。早期的觀點(diǎn)認(rèn)為在DC病理生理改變中,心肌破壞的主要形式為心肌細(xì)胞壞死,而隨后大量的研究發(fā)現(xiàn),心肌壞死更多發(fā)生在心肌梗塞的急性期等急性病變中,而糖尿病的心肌病理改變是慢性長(zhǎng)期的過(guò)程,主要表現(xiàn)為心肌間質(zhì)纖維化、心肌細(xì)胞肥大和心肌細(xì)胞凋亡,其中心肌細(xì)胞凋亡在DC的發(fā)生發(fā)展中占據(jù)主要地位[1,2],故抑制心肌細(xì)胞凋亡應(yīng)是臨床防治糖尿病性心肌病的關(guān)鍵。在既往的研究中已發(fā)現(xiàn)上調(diào)脂聯(lián)素途徑關(guān)鍵蛋白脂聯(lián)素受體連接蛋白1(APPL1)可改善糖尿病性心肌病[3],進(jìn)一步的研究發(fā)現(xiàn)脂聯(lián)素途徑保護(hù)心血管系統(tǒng)作用環(huán)節(jié)在于激活脂聯(lián)素信號(hào)途徑中的APPL1-AMPK軸,抑制核因子NF-?B的表達(dá)[4,5]。此外,其他實(shí)驗(yàn)室和我們均已發(fā)現(xiàn)脂聯(lián)素信號(hào)途徑中的PPARα能抑制NF-?B,直接參與防止糖尿病心肌細(xì)胞凋亡[6],而PPARα為AMPK的重要信號(hào)下游分子。據(jù)此,我們推測(cè)在脂聯(lián)素途徑中可能存在“APPL1-AMPK-PPARα軸”,其在防止糖尿病心肌細(xì)胞凋亡方面可能占有重要地位。又有研究發(fā)現(xiàn)胰高血糖素樣肽-1(GLP-1)對(duì)心血管系統(tǒng)有一定保護(hù)作用,可以減少包括糖尿病心肌細(xì)胞的凋亡,并可促進(jìn)脂聯(lián)素的分泌,且該作用獨(dú)立于降糖效應(yīng)之外[7-9]。因此,現(xiàn)在廣泛認(rèn)可的觀點(diǎn)是GLP-1具有對(duì)糖尿病患者心血管保護(hù)作用,其機(jī)制可能與激活脂聯(lián)素途徑有關(guān),我們進(jìn)一步推測(cè)GLP-1可能具有減少糖尿病心肌細(xì)胞凋亡的作用,其作用機(jī)制在于激活心肌細(xì)胞脂聯(lián)素信號(hào)通路,活化APPL1-AMPK-PPARα軸。為證明我們的設(shè)想,本實(shí)驗(yàn)擬從臨床觀察、動(dòng)物模型和細(xì)胞水平進(jìn)行深入研究。目前,臨床上尚無(wú)明確的糖尿病性心肌病的診斷標(biāo)準(zhǔn),主要以心功能參數(shù)作為參考指標(biāo)。我們擬首先收集臨床2型糖尿病病例,并與正常體檢人群對(duì)照,探索2型糖尿病患者血清脂聯(lián)素水平變化與心功能參數(shù)改變的相關(guān)關(guān)系。其次擬通過(guò)小劑量鏈脲佐菌素(stz)+高脂飲食誘導(dǎo)2型糖尿病大鼠模型,予以glp-1受體激動(dòng)劑艾塞那肽為干預(yù)措施,觀察艾塞那肽對(duì)糖尿病心肌細(xì)胞凋亡的影響,并觀察艾塞那肽通過(guò)調(diào)節(jié)脂聯(lián)素途徑關(guān)鍵連接蛋白appl1水平影響心肌細(xì)胞凋亡的作用。最后,在培養(yǎng)大鼠原代心肌細(xì)胞中檢測(cè)艾塞那肽對(duì)心肌細(xì)胞脂聯(lián)素信號(hào)途徑的激活作用及對(duì)細(xì)胞凋亡的影響。目的觀察2型糖尿病血清脂聯(lián)素水平與心臟功能之間的相關(guān)關(guān)系以及艾塞那肽對(duì)心肌細(xì)胞凋亡的影響,闡明艾塞那肽通過(guò)激活脂聯(lián)素途徑改善糖尿病性心肌病的作用及其機(jī)制。方法1.收集2型糖尿病患者及健康體檢者的臨床基本資料,采集患者空腹靜脈血,elisa法檢測(cè)血清高分子量脂聯(lián)素水平,增強(qiáng)磁共振測(cè)定患者心功能指標(biāo);2.構(gòu)建2型糖尿病sd大鼠模型,高脂飲食喂養(yǎng),分為正常對(duì)照組(n組),糖尿病組(d組),糖尿病加胰島素治療組(di組),糖尿病加艾塞那肽治療組(de組),成模后干預(yù)12周,取大鼠髂靜脈血,elisa法測(cè)定血清胰島素、脂聯(lián)素,多媒體生物信號(hào)記錄儀測(cè)定血流動(dòng)力學(xué),tuenl法檢測(cè)心肌細(xì)胞凋亡變化,取心臟組織行免疫組化及western-blotting檢測(cè)信號(hào)分子appl1、ampk、pparα、nf-?b表達(dá)水平;3.培養(yǎng)原代鼠心肌細(xì)胞,分為正常對(duì)照組(c組),高糖高脂組(d組),高糖高脂+艾塞那肽組(de組),高糖高脂+艾塞那肽+appl1過(guò)表達(dá)腺病毒組(oe組),高糖高脂+艾塞那肽+appl1干擾腺病毒組(bl組),elisa法測(cè)定細(xì)胞培養(yǎng)液中高分子量脂聯(lián)素水平,tuenl法檢測(cè)原代心肌細(xì)胞凋亡變化,取心肌細(xì)胞行western-blotting檢測(cè)信號(hào)分子appl1、ampk、pparα、nf-?b表達(dá)水平。結(jié)果本實(shí)驗(yàn)共收集到30例2型糖尿病患者(t2dm組)及30例健康體檢患者(n組),兩組患者一般資料無(wú)明顯差異,t2dm組患者糖化血糖水平(hba1c)、空腹血糖水平、homa-ir指數(shù)明顯高于n組患者,c肽水平低于n組患者,而兩組間胰島素水平無(wú)明顯統(tǒng)計(jì)學(xué)差異。t2dm組患者血清hdl水平(1.23±0.40mmol/l)明顯低于n組患者(1.61±0.45mmol/l),tg水平(3.73±3.44mmol/l)明顯高于n組患者(1.56±0.86mmol/l),差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。二組患者的tc及l(fā)dl水平無(wú)差別(p0.05)。t2dm組患者血清高分子量脂聯(lián)素水平(10.83±2.81mg/l)明顯低于n組(14.90±3.26mg/l)(p0.05)。經(jīng)心臟增強(qiáng)磁共振檢測(cè),t2dm組患者心臟左室舒張末期容積(edv)(59.70±7.26ml/m2)及每搏輸出量(sv)(34.77±6.48ml/m2)較n組edv(65.84±9.67ml/m2)及sv(38.40±4.75ml/m2)降低,而收縮末期容積(esv)(29.00±6.60ml/m2)較n組(24.25±5.51ml/m2)明顯增加,差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。相關(guān)分析顯示高分子量脂聯(lián)素水平與糖尿病患者每搏輸出量之間存在一定的正相關(guān)關(guān)系[r=0.376,p=0.041]。在動(dòng)物實(shí)驗(yàn)中,di組及de組血糖較d組明顯下降,血清胰島素上升,差異均有統(tǒng)計(jì)學(xué)意義(p0.05),而di與de兩組間血糖水平無(wú)明顯差異。d組及di組血清高分子量脂聯(lián)素水平較n組明顯下降,de組血清高分子量脂聯(lián)素水平較di組明顯上升,差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。d組心肌細(xì)胞凋亡率(55.71%±3.84%)明顯增加,de組大鼠心肌細(xì)胞凋亡率(27.43%±3.63%)明顯下降,而與de組比較,di組大鼠心肌細(xì)胞凋亡率(43.91%±4.23%)明顯升高。心功能檢測(cè)顯示相較于c組,d組大鼠心臟lvsp(105.87±4.08mmhg)及di組大鼠心臟lvsp(107.19±4.09mmhg)明顯降低,而d組大鼠心臟lvedp(17.62±1.74mmhg)及di組大鼠心臟lvedp(17.48±1.49mmhg)明顯增加,差異均具有統(tǒng)計(jì)學(xué)意義(p0.05)。相較于di組,de組大鼠心臟lvsp(119.11±5.11mmhg)明顯增加,而lvedp(13.64±1.25mmhg)明顯降低,差異具有統(tǒng)計(jì)學(xué)意義(p0.05)。對(duì)心肌細(xì)胞信號(hào)分子的檢測(cè)顯示相較于c組,d組及di組心肌appl1、p-ampk、pparα表達(dá)量均明顯降低,但nf-?b表達(dá)量較c組明顯升高。de組appl1、p-ampk、pparα表達(dá)量分別為0.65±0.02、0.78±0.04、1.72±0.05,較d組及di組明顯增加,de組大鼠心肌nf-?b表達(dá)量較d組和di組心肌明顯升高,差異有統(tǒng)計(jì)學(xué)意義(p0.05)。細(xì)胞實(shí)驗(yàn)中,我們發(fā)現(xiàn)心肌細(xì)胞具有自分泌脂聯(lián)素的能力,并觀察到de組、oe組、bl組大鼠細(xì)胞上清高分子量脂聯(lián)素水平分別為9.40±0.16mg/l、8.70±0.34mg/l、和9.30±0.30mg/l,較d組明顯上升(p0.05),de、oe、bl組細(xì)胞上清脂聯(lián)素水平比較差異沒(méi)有統(tǒng)計(jì)學(xué)意義(p0.05)。但細(xì)胞凋亡檢測(cè)結(jié)果提示de組細(xì)胞凋亡(20%~29%)較d組(34%~42%)有降低趨勢(shì)。oe組中這種趨勢(shì)更加明顯(18%~24%),但相反的bl組細(xì)胞凋亡率較de組明顯上升(43%~52%),差異均有統(tǒng)計(jì)學(xué)意義(p0.05)。另外,各組心肌細(xì)胞appl1、p-ampk、pparα、nf-?b檢測(cè)結(jié)果與動(dòng)物實(shí)驗(yàn)結(jié)果具有相同變化趨勢(shì)。結(jié)論2型糖尿病患者心臟收縮及舒張功能受損與循環(huán)中高分子量脂聯(lián)素水平降低密切相關(guān),運(yùn)用glp-1受體激動(dòng)劑艾塞那肽干預(yù)糖尿病后通過(guò)上調(diào)血清和心肌細(xì)胞自分泌脂聯(lián)素水平及激活A(yù)PPL1-AMPK-PPARα軸信號(hào)通路,抑制了心肌細(xì)胞內(nèi)NF-?B活化和心肌細(xì)胞凋亡,改善糖尿病心肌功能。
[Abstract]:Background Diabetic cardiomyopathy (DC), originally described by Rubler in 1972, is defined as a specific cardiomyopathy caused by diabetes without coronary artery disease, hypertension or other underlying causes. It is often characterized by decreased cardiac compliance, diastolic filling impairment or systolic dysfunction. Blood glucose and related metabolic disorders can directly damage the myocardium and lead to DC, so patients with diabetic cardiovascular complications can be combined with DC. Clinically, DC has a large number of patients, causing great harm to patients. A large number of studies have found that myocardial necrosis occurs more in the acute phase of myocardial infarction and other acute lesions, and diabetic myocardial pathological changes are a chronic long-term process, mainly manifested as myocardial interstitial fibrosis, cardiomyocyte hypertrophy and cardiomyocyte apoptosis, in which cardiomyocyte apoptosis plays a major role in the occurrence and development of DC [1,2]. It has been found that up-regulation of adiponectin pathway key protein adiponectin receptor connexin 1 (APPL1) can improve diabetic cardiomyopathy [3]. Further studies have found that adiponectin pathway protects cardiovascular system by activating lipids. The APPL1-AMPK axis in the adiponectin signaling pathway inhibits the expression of nuclear factor NF-? B [4,5]. In addition, other laboratories and we have found that PPARa in the adiponectin signaling pathway inhibits NF-? B and directly participates in the prevention of apoptosis of diabetic cardiomyocytes [6]. PPARa is an important downstream molecule of AMPK signal. There may be an "APPL1-AMPK-PPAR alpha axis" which may play an important role in preventing apoptosis of diabetic cardiomyocytes. Some studies have found that glucagon-like peptide-1 (GLP-1) has a protective effect on cardiovascular system, which can reduce apoptosis of cardiomyocytes including diabetes mellitus and promote adiponectin secretion, and this effect is independent of Therefore, it is widely accepted that GLP-1 has cardiovascular protective effects in diabetic patients. The mechanism may be related to the activation of adiponectin pathway. We further speculate that GLP-1 may reduce the apoptosis of diabetic cardiomyocytes by activating adiponectin signaling pathway. To prove our hypothesis, we intend to conduct in-depth study from clinical observation, animal model and cell level. At present, there is no definite clinical diagnostic criteria for diabetic cardiomyopathy, mainly with cardiac function parameters as reference indicators. We intend to collect clinical type 2 diabetes mellitus cases and with normal. To explore the relationship between serum adiponectin level and cardiac function parameters in type 2 diabetes mellitus (T2DM) patients. Secondly, the model of type 2 diabetes mellitus (DM) rats was induced by low-dose streptozotocin (stz) + high-fat diet, and the intervention of GLP-1 receptor agonist exenatide was given to observe the effect of exenatide on diabetic cardiomyocyte apoptosis. Aim To observe the effect of exenatide on apoptosis of cardiomyocytes by regulating the level of key connexin appl 1 in adiponectin pathway. The relationship between diabetic cardiomyopathy and adiponectin level and cardiac function, and the effect of exenatide on cardiomyocyte apoptosis were studied to elucidate the effect and mechanism of exenatide on diabetic cardiomyopathy by activating adiponectin pathway. Methods Serum high-molecular-weight adiponectin levels were detected and cardiac function indexes were measured by enhanced magnetic resonance imaging (MRI). 2. The model of type 2 diabetes mellitus (DM) rats were established and fed with high-fat diet. The rats were divided into normal control group (n group), diabetic group (d group), diabetic plus insulin group (di group), diabetic plus exenatide group (de group). The levels of serum insulin and adiponectin were measured by elisa, the hemodynamics was measured by multimedia bio-signal recorder, the changes of cardiomyocyte apoptosis were detected by tuenl, and the expressions of appl-1, ampk, PPAR-a and NF-B were detected by immunohistochemistry and western-blotting. 3. Group c, group d, group de, group oe, group bl, group d, group d, group d, group d, group de, group oe, group b, group b, group d, group d, group d, group d, group d, group d, group d, group c, group d, group d, group d, group d, group d, group c, group d, group c, group d, group d, group d, group d, group d, group c, group d, group d, group d, group d, group d, group c, group d, group d, group c, group c, group d, group c, group c, group Western-blotting was used to detect the expression of appl-1, ampk, PPAR-a and nf-b. Results 30 patients with type 2 diabetes mellitus (t2dm group) and 30 healthy people (n group) were collected. There was no significant difference in the general data between the two groups. The levels of hba1c, fasting blood glucose and HOMA-IR index in T2DM group were significantly higher than those in n group. The level of serum HDL (1.23 + 0.40 mmol / l) in T2DM group was significantly lower than that in N group (1.61 + 0.45 mmol / l), and the level of TG (3.73 + 3.44 mmol / l) was significantly higher than that in N group (1.56 + 0.86 mmol / l), the difference was statistically significant (p0.05). Serum high-molecular-weight adiponectin (10.83 (+ 2.81 mg / l)) in T2DM group was significantly lower than that in N group (14.90 (+ 3.26 mg / l) (p0.05). left ventricular end-diastolic volume (edv) (59.70 (+ 7.26 ml / m2) and stroke output (sv) (34.77 (+ 6.48 ml / m2)) in T2DM group were significantly lower than that in N group (65.84 (+ 9.67 ml / m2) and SV (38.4) by cardiac contrast-enhanced magnetic resonance imaging. The end systolic volume (esv) (29.00 + 6.60ml / m2) was significantly higher than that of N group (24.25 + 5.51ml / m2). correlation analysis showed that there was a positive correlation between high molecular weight adiponectin level and stroke output of diabetic patients [r = 0.376, P = 0.041]. The levels of high molecular weight adiponectin in group D and di were significantly lower than those in group n, and the levels of high molecular weight adiponectin in group de were significantly higher than those in group di (p0.05). Myocyte apoptosis rate (55.71% + 3.84%) was significantly increased, myocardial apoptosis rate (27.43% + 3.63%) was significantly decreased in de group, and myocardial apoptosis rate (43.91% + 4.23%) was significantly increased in di group compared with de group. cardiac function test showed that compared with C group, LVSP (105.87 + 4.08mmhg) in D group and LVSP (107.19 + 4.09mmhg) in Di Group rats. LVEDP (17.62 + 1.74 mmhg) in group D and LVEDP (17.48 + 1.49 mmhg) in group Di were significantly increased (p0.05). LVSP (119.11 + 5.11 mmhg) in group de was significantly increased, while LVEDP (13.64 + 1.25 mmhg) in group Di was significantly decreased (p0.05). Compared with group c, the expression of appl-1, p-ampk and PPAR-a in myocardium of group D and di decreased significantly, but the expression of NF-B increased significantly. the expression of appl-1, p-ampk and PPAR-a in myocardium of group de were 0.65 (+) 0.02, 0.78 (+) 0.04, 1.72 (+) 0.05) respectively, which were significantly higher than that of group D and di. the expression of NF-B in myocardium of group de was significantly higher than that of group D and di. The level of high molecular weight adiponectin in the supernatant of de group, OE group and BL group was 9.40 (+ 0.16 mg / l), 8.70 (+ 0.34 mg / l) and 9.30 (+ 0.30 mg / l) respectively, which was significantly higher than that of D group (p0.05), de, OE and BL group (p0.05). There was no significant difference in serum adiponectin levels (p0.05). however, the results of apoptosis detection showed that apoptosis in de group (20% ~ 29%) was lower than that in D group (34% ~ 42%). The results of appl-1, p-ampk, PPAR-alpha and NF-B in cardiomyocytes of group 2 showed the same trend as those of animal experiment. Conclusion The impairment of cardiac systolic and diastolic function in type 2 diabetes mellitus is closely related to the decrease of circulating high molecular weight adiponectin levels. Cell autocrine adiponectin level and activation of APPL1-AMPK-PPARalpha axis signaling pathway inhibited the activation of NF-? B and myocardial cell apoptosis, and improved diabetic myocardial function.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.2

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5 陳吉球,梁麗凡,肖軍,張?jiān)鹿?心肌細(xì)胞凋亡的研究進(jìn)展[J];國(guó)外醫(yī)學(xué)(生理、病理科學(xué)與臨床分冊(cè));2000年05期

6 張曉敏;缺血再灌注與心肌細(xì)胞凋亡的研究進(jìn)展[J];廣東醫(yī)學(xué);2002年02期

7 杜先華,楊芳炬;中藥對(duì)心肌細(xì)胞凋亡的保護(hù)作用[J];中藥新藥與臨床藥理;2002年06期

8 呂澤平,李俊峽,賈國(guó)良;心臟疾病與心肌細(xì)胞凋亡研究進(jìn)展[J];臨床薈萃;2002年04期

9 金莉,王國(guó)中;心肌細(xì)胞凋亡的研究進(jìn)展[J];齊齊哈爾醫(yī)學(xué)院學(xué)報(bào);2003年10期

10 吳青,陶宏凱,陶大昌,閆新林,李巧云,周祖玉;缺血再灌注誘導(dǎo)心肌細(xì)胞凋亡及凋亡相關(guān)基因表達(dá)的研究[J];中國(guó)心血管病研究雜志;2004年11期

中國(guó)重要會(huì)議論文全文數(shù)據(jù)庫(kù) 前10條

1 趙宇光;李薇;;基質(zhì)細(xì)胞衍生因子-1β對(duì)高脂誘導(dǎo)心肌細(xì)胞凋亡的預(yù)防作用及機(jī)制[A];第13屆全國(guó)實(shí)驗(yàn)血液學(xué)會(huì)議論文摘要[C];2011年

2 王筠;劉暢;;內(nèi)質(zhì)網(wǎng)應(yīng)激在高糖誘導(dǎo)乳鼠心肌細(xì)胞凋亡中的作用[A];中華醫(yī)學(xué)會(huì)第十次全國(guó)內(nèi)分泌學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2011年

3 呂秀秀;王華東;余小慧;;小檗堿抑制去甲腎上腺素誘導(dǎo)心肌細(xì)胞凋亡的機(jī)制研究[A];中國(guó)病理生理學(xué)會(huì)第九屆全國(guó)代表大會(huì)及學(xué)術(shù)會(huì)議論文摘要[C];2010年

4 張峰;梁宏;祁章年;黃增明;張曉春;張恒太;王根良;;γ射線全身照射對(duì)小鼠血液和心肌細(xì)胞凋亡的影響[A];中國(guó)空間科學(xué)學(xué)會(huì)空間生命專業(yè)委員會(huì)2003年中國(guó)空間生命科學(xué)與航天醫(yī)學(xué)會(huì)議論文摘要集[C];2003年

5 張璐潔;呂進(jìn)泉;;心梗局部高表達(dá)整合素連接激酶抑制心肌細(xì)胞凋亡改善心臟收縮功能[A];2012年江浙滬兒科學(xué)術(shù)年會(huì)暨浙江省醫(yī)學(xué)會(huì)兒科學(xué)分會(huì)學(xué)術(shù)年會(huì)、兒內(nèi)科疾病診治新進(jìn)展國(guó)家級(jí)學(xué)習(xí)班論文匯編[C];2012年

6 師綠江;尹昭云;洪欣;辛益妹;賀鵬飛;任宏偉;韓行湛;關(guān)景芳;;金屬硫蛋白對(duì)加速度致心肌細(xì)胞凋亡的影響[A];中國(guó)生理學(xué)會(huì)第六屆應(yīng)用生理學(xué)委員會(huì)全國(guó)學(xué)術(shù)會(huì)議論文摘要匯編[C];2003年

7 龐錦江;許榮q;徐向斌;曹濟(jì)民;趙三妹;單惠敏;陳晨;;Hexarelin對(duì)血管緊張素Ⅱ誘導(dǎo)離體心肌細(xì)胞凋亡的抑制作用[A];中國(guó)生理學(xué)會(huì)肥胖的臨床與基礎(chǔ)暨神經(jīng)免疫內(nèi)分泌學(xué)術(shù)研討會(huì)論文摘要匯編[C];2003年

8 蔣東;鄭世營(yíng);葛錦峰;趙軍;;缺血預(yù)處理減輕在體家兔心肌細(xì)胞凋亡[A];中華醫(yī)學(xué)會(huì)第七次全國(guó)胸心血管外科學(xué)術(shù)會(huì)議暨2007中華醫(yī)學(xué)會(huì)胸心血管外科青年醫(yī)師論壇論文集心血管外科分冊(cè)[C];2007年

9 董建文;丁海雷;朱海峰;朱衛(wèi)中;周兆年;;間歇性低氧減少缺血再灌注引起的大鼠心肌細(xì)胞凋亡[A];中國(guó)生理學(xué)會(huì)第21屆全國(guó)代表大會(huì)暨學(xué)術(shù)會(huì)議論文摘要匯編[C];2002年

10 龐錦江;許榮q;徐向斌;曹濟(jì)民;趙三妹;單惠敏;陳晨;;Hexarelin對(duì)血管緊張素Ⅱ誘導(dǎo)離體心肌細(xì)胞凋亡的抑制作用[A];中國(guó)生理學(xué)會(huì)第六屆應(yīng)用生理學(xué)委員會(huì)全國(guó)學(xué)術(shù)會(huì)議論文摘要匯編[C];2003年

中國(guó)重要報(bào)紙全文數(shù)據(jù)庫(kù) 前3條

1 本報(bào)記者 慕欣;PNS可否抑制心肌細(xì)胞凋亡？[N];醫(yī)藥經(jīng)濟(jì)報(bào);2010年

2 記者 鄭福漢 見(jiàn)習(xí)記者 甘青;執(zhí)著的追求[N];咸寧日?qǐng)?bào);2006年

3 記者 王丹;防治心肌梗死有新靶點(diǎn)[N];健康報(bào);2011年

中國(guó)博士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

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2 康波;硫化氫通過(guò)miR-1-Bcl-2通路抑制缺血再灌注心肌細(xì)胞調(diào)亡的實(shí)驗(yàn)研究[D];第二軍醫(yī)大學(xué);2015年

3 王琳;氯離子通道阻斷劑對(duì)內(nèi)質(zhì)網(wǎng)應(yīng)激誘導(dǎo)心肌細(xì)胞凋亡的保護(hù)作用及分子機(jī)制[D];第四軍醫(yī)大學(xué);2015年

4 叢曉強(qiáng);低劑量聯(lián)麥氧釩調(diào)節(jié)高糖誘導(dǎo)內(nèi)質(zhì)網(wǎng)應(yīng)激減輕心肌損傷作用的研究[D];吉林大學(xué);2016年

5 望廬山;基于PI3K/Akt通路探討“標(biāo)本配穴”電針干預(yù)心肌細(xì)胞凋亡的實(shí)驗(yàn)研究[D];湖北中醫(yī)藥大學(xué);2016年

6 江雪;可溶性高級(jí)糖基化終末產(chǎn)物受體通過(guò)JAK2/STAT3通路抑制心肌缺血再灌注誘導(dǎo)的心肌細(xì)胞凋亡的研究[D];首都醫(yī)科大學(xué);2016年

7 張?jiān)弃Q;體外心臟震波治療在大鼠急性心肌梗死心肌細(xì)胞凋亡中的作用和機(jī)制研究[D];北京協(xié)和醫(yī)學(xué)院;2016年

8 萬(wàn)春云;過(guò)氧化氫誘導(dǎo)雞心肌細(xì)胞凋亡的轉(zhuǎn)錄組學(xué)研究[D];華中農(nóng)業(yè)大學(xué);2016年

9 盧青;枸櫞酸預(yù)處理對(duì)缺血再灌注大鼠心肌細(xì)胞凋亡和再灌注心律失常的影響及其分子機(jī)制研究[D];南方醫(yī)科大學(xué);2016年

10 李國(guó)華;PI3K-PKB/Akt-GSK-3β信號(hào)通路在FGF-2心肌保護(hù)中的作用研究[D];南華大學(xué);2016年

中國(guó)碩士學(xué)位論文全文數(shù)據(jù)庫(kù) 前10條

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2 葛晨;微小RNA-214對(duì)膿毒癥小鼠心肌損傷的作用[D];河北醫(yī)科大學(xué);2015年

3 馬苗苗;β3-AR對(duì)心肌細(xì)胞凋亡的影響及介導(dǎo)機(jī)制研究[D];石河子大學(xué);2015年

4 王偉濤;SP600125對(duì)腦死亡大鼠心肌細(xì)胞凋亡的保護(hù)作用及其機(jī)制研究[D];鄭州大學(xué);2015年

5 王娟;二甲基甲酰胺通過(guò)線粒體通路誘導(dǎo)H9c2心肌細(xì)胞凋亡的實(shí)驗(yàn)研究[D];安徽醫(yī)科大學(xué);2015年

6 郁U，

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