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慢性應(yīng)激引發(fā)的高血壓及深靜脈血栓機制的研究

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  本文選題:腎交感神經(jīng) + 足底電擊; 參考:《蘇州大學(xué)》2015年碩士論文


【摘要】:第一部分:大鼠腎交感神經(jīng)與腎素血管緊張素系統(tǒng)在慢性應(yīng)激引發(fā)的高血壓中的作用目的:在防治高血壓病的研究中,科研人員發(fā)現(xiàn)長期慢性應(yīng)激會嚴(yán)重影響患者的身心健康,使機體處于亞健康狀態(tài),乃至引發(fā)應(yīng)激性高血壓。研究證明,腎交感神經(jīng)系統(tǒng)(RSNS)與腎素血管緊張素系統(tǒng)(RAS)在腎性高血壓和自發(fā)性高血壓的發(fā)病過程中起到了關(guān)鍵的作用,目前國內(nèi)外關(guān)于應(yīng)激性高血壓發(fā)病機制的報道較少。本實驗將致力于探究腎交感神經(jīng)系統(tǒng)與腎素血管緊張素系統(tǒng)在應(yīng)激性高血壓中的作用機制。方法:我們將90只SD大鼠隨機平均分為6組(n=15):①空白對照組,②長期慢性足底電擊組(電擊組),③腎交感神經(jīng)切除組,④腎交感神經(jīng)切除+長期慢性電擊組(腎交感神經(jīng)切除電擊組),⑤加血管緊張素轉(zhuǎn)換酶1抑制劑(卡托普利)+長期慢性電擊組(卡托普利電擊組),⑥加抗氧化劑-4-羥基-2,2,6,6-四甲基哌啶-1-氧自由基(superoxide dismutase mimetic,Tempol)+長期慢性電擊組(Tempol電擊組)。對電擊組大鼠進行足底電擊14天。測定大鼠的血壓。測定各組大鼠血漿中應(yīng)激激素皮質(zhì)酮(corticosterone)和腎臟中應(yīng)激激素去甲腎上腺素(noradrenaline,NE)的含量。測定各組大鼠外周RAS水平的變化,即測定血漿中腎素(renin),血管緊張素II(angiotensin II,Ang II)的含量。測定各組大鼠中樞RAS水平的變化,即分別對大腦皮層和下丘腦中RAS中的成員進行轉(zhuǎn)錄和翻譯水平的分析。測定各組大鼠血漿中氧化應(yīng)激產(chǎn)物硫代巴比妥酸反應(yīng)物(thiobarbituric acid reactive substances,TBARS)的含量。測定各組大鼠血漿中抗氧化酶超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽過氧化物酶(glutathione peroxidase,GSH-Px)的活性。結(jié)果:1.與對照組大鼠相比,電擊組大鼠血壓出現(xiàn)顯著性升高,腎交感神經(jīng)切除電擊組,加卡托普利電擊組以及加Tempol電擊組大鼠的血壓均未出現(xiàn)顯著升高。2.電擊兩周后大鼠血漿中皮質(zhì)酮,腎臟中去甲腎上腺素含量顯著升高,大鼠處于應(yīng)激狀態(tài),腎交感神經(jīng)切除電擊組,加卡托普利電擊組以及加Tempol電擊組大鼠應(yīng)激激素均未顯著性升高。3.與對照組相比,電擊組大鼠血漿中腎素,Ang II的濃度顯著升高,腎交感神經(jīng)切除電擊組,加卡托普利電擊組以及加Tempol電擊組大鼠的血壓均未顯著升高。4.與對照組相比,電擊組大鼠大腦皮層及下丘腦中血管緊張素原(angiotensinogen,AGT),血管緊張素轉(zhuǎn)換酶1(angiotensin converting enzyme 1,ACE1),血管緊張素轉(zhuǎn)換酶2(angiotensin converting enzyme 2,ACE2),血管緊張素受體1a(angiotensin II receptor 1a,AT1a)的信使RNA(m RNA)表達(dá)量與蛋白質(zhì)表達(dá)量均顯著升高,數(shù)據(jù)顯示,交感神經(jīng)切除處理與抗氧化處理后,無論是在外周還是中樞,大鼠腎素血管緊張素系統(tǒng)均受到了顯著的抑制。5.與對照組相比,大鼠血漿中TBARS的含量顯著升高,而血漿中SOD,GSH-Px的活性顯著降低,大鼠的氧化/抗氧化系統(tǒng)失衡,氧化水平升高,腎交感神經(jīng)切除電擊組,加卡托普利電擊組以及加Tempol電擊組大鼠的氧化水平未見升高。結(jié)論:腎交感神經(jīng)系統(tǒng),腎素血管緊張素系統(tǒng)與氧化應(yīng)激在慢性應(yīng)激誘導(dǎo)的高血壓的發(fā)生過程中起著重要作用;腎素血管緊張素系統(tǒng),腎交感神經(jīng)系統(tǒng)與氧化應(yīng)激這三者相互影響并共同參與慢性應(yīng)激誘導(dǎo)的高血壓的發(fā)生。第二部分:大鼠腎交感神經(jīng)與氧化應(yīng)激在慢性應(yīng)激引發(fā)的深靜脈血栓中的作用目的:深靜脈血栓(deep vein thrombosis of lower extremity,DVT)是指血液在深靜脈腔內(nèi)非正常凝結(jié),是心血管疾病中的常見病、多發(fā)病,在我國DVT的患病率以及確診率近年來呈現(xiàn)出逐年遞增的趨勢,因此探討其發(fā)病原因,對DVT的預(yù)防和治療有著重要意義。本實驗將致力于探究慢性應(yīng)激誘導(dǎo)的DVT中的發(fā)病機制。方法:我們將60只SD大鼠隨機平均分為4組(n=15):對照組,電擊組,腎交感神經(jīng)切除電擊組,加Tempol電擊組。測定各組大鼠血漿中應(yīng)激激素皮質(zhì)酮和腎臟中應(yīng)激激素去甲腎上腺素的含量。測定各組大鼠血漿中氧化應(yīng)激產(chǎn)物TBARS的含量;測定各組大鼠血漿中抗氧化酶SOD和GSH-Px的活性。使用凝血分析儀測量凝血酶原時間(prothrombin time,PT),活化部分凝血活酶時間(activated partial prothrombin time,APPT)和凝血酶時間(thrombin time,TT)。使用血小板聚集儀分別測量腺苷二磷酸(ADP)和膠原蛋白(collagen)刺激下的血小板聚集時間,計算血小板聚集率。下腔靜脈結(jié)扎法制造深靜脈血栓模型,取血栓測定血栓的重量。結(jié)果:1.電擊兩周后大鼠血漿中皮質(zhì)酮,腎臟中去甲腎上腺素含量顯著升高,大鼠處于應(yīng)激狀態(tài),腎交感神經(jīng)切除電擊組,以及加Tempol電擊組大鼠應(yīng)激激素均未顯著性升高。2.與對照組相比,電擊組大鼠血漿中TBARS的含量顯著升高,而血漿中SOD,GSH-Px的活性顯著降低,大鼠的氧化/抗氧化系統(tǒng)失衡,氧化水平升高,腎交感神經(jīng)切除電擊組,以及加Tempol電擊組大鼠氧化水平未見升高。3.與對照組相比,電擊組大鼠的TT顯著升高。4.與對照組相比,電擊組大鼠在ADP和collagen刺激下的血小板聚集率顯著升高,腎交感神經(jīng)切除處理與抗氧化處理后,ADP和collagen刺激下的血小板聚集率未出現(xiàn)顯著升高。5.與對照組相比,電擊組大鼠深靜脈血栓的重量顯著升高,腎交感神經(jīng)切除電擊組以及加Tempol電擊組血栓的重量未見顯著升高。結(jié)論:在交感神經(jīng)系統(tǒng)和氧化應(yīng)激的協(xié)同參與下,足底電擊引發(fā)深靜脈血栓。
[Abstract]:Part one: the role of the rat renal sympathetic and renin angiotensin system in the hypertension induced by chronic stress: in the study of the prevention and treatment of hypertension, the researchers found that chronic chronic stress will seriously affect the physical and mental health of the patients, make the body in the subhealth state, and even lead to stress hypertension. The renal sympathetic nervous system (RSNS) and renin angiotensin system (RAS) play a key role in the pathogenesis of renal hypertension and spontaneous hypertension. There are few reports on the pathogenesis of stress-induced hypertension at home and abroad. This experiment will be devoted to exploring the stress of the renal sympathetic nervous system and renin angiotensin system in stress. Mechanism of action in sexual hypertension. Methods: We divided 90 SD rats randomly into 6 groups (n=15): (1) blank control group, (2) chronic chronic foot shock group (electric shock group), renal sympathetic excision group, kidney sympathectomy + long-term chronic electric shock group (renal sympathetic excision group), and 5 angiotensin converting enzyme 1 inhibitor ( Kato Pury) + long-term chronic electric shock group (Kato Pury electric shock group), plus antioxidant -4- hydroxyl -2,2,6,6- four methylpiperidine -1- oxygen free radical (superoxide dismutase mimetic, Tempol) + long-term chronic electric shock group (Tempol shock group). The rats in the electric shock group were subjected to the electric shock of the foot. The blood pressure of rats was measured. The stress in the plasma of rats was measured. The content of hormone corticosterone (corticosterone) and the stress hormone norepinephrine (noradrenaline, NE) in the kidney. The changes in the peripheral RAS level of rats in each group, that is, the content of the plasma renin (renin), the angiotensin II (angiotensin II, Ang II), and the changes in the central RAS level of the rats in each group, that is, the cerebral cortex and the lower part of the brain, respectively. Analysis of the transcriptional and translation levels of members of RAS in the thalamus. Determination of the content of thiobarbituric acid reactive substances (TBARS) in the plasma of rats in each group. Determination of the antioxidant enzyme superoxide dismutase (superoxide dismutase, SOD) and glutathione peroxy in the plasma of each group The activity of glutathione peroxidase (GSH-Px). Results: 1. compared with the control group, the blood pressure of the rats in the electric shock group was significantly higher than that in the control group. The blood pressure of the renal sympathetic excision group, the captopril group and the Tempol electric shock group did not significantly increase the plasma corticosterone in the plasma of the rats after the shock of the.2. electric shock and the kidney in the kidney after two weeks. The content of norepinephrine increased significantly, the rats were in the stress state, the renal sympathetic nerve excision group, the captopril group and the Tempol group did not significantly increase the stress hormone.3. and the control group. Compared with the control group, the concentration of the renin, Ang II in the plasma of the electric shock group was significantly increased, the renal sympathetic excision and electric shock group, and the card was added. The blood pressure of the rats in the Topley electric shock group and the Tempol group did not increase significantly. Compared with the control group, the angiotensin converting enzyme 1 (angiotensin converting enzyme 1, ACE1), angiotensin converting enzyme 2 (angiotensin converting enzyme) and the angiotensin converting enzyme 2 (angiotensin converting enzyme) were compared with the control group. 2, ACE2), the expression of the messenger RNA (m RNA) of the angiotensin receptor 1A (angiotensin II receptor 1a, AT1a) increased significantly and the protein expression level. The data showed that the renin angiotensin system in the rat was significantly inhibited by the renin angiotensin system, both in the peripheral and in the center, after sympathetic resection and antioxidant treatment. The content of TBARS in the plasma of rats increased significantly, while the activity of SOD and GSH-Px in the plasma was significantly reduced, the oxidative / antioxidant system in rats was unbalance, the level of oxidation increased, the renal sympathetic excision group, the captopril group and the Tempol group had not increased the level of oxidation. Conclusion: the renal sympathetic nervous system, renin blood The angiotensin system and oxidative stress play an important role in the process of chronic stress induced hypertension; the renin angiotensin system, the renal sympathetic nervous system and oxidative stress are three interrelated and participate in the occurrence of hypertension induced by chronic stress. The second part: the renal sympathetic and oxidative stress in rats are slow The purpose of deep venous thrombosis caused by sexual stress: deep vein thrombosis of lower extremity (DVT) refers to the abnormal condensation of blood in the deep vein cavity. It is a common disease in cardiovascular disease. It is a common disease. The prevalence and diagnosis rate of DVT in China have been increasing year by year in recent years. Therefore, the development of its hair is discussed. The cause of the disease is of great significance for the prevention and treatment of DVT. This experiment will be devoted to exploring the pathogenesis of chronic stress induced DVT. Methods: We divided 60 SD rats into 4 groups at random (n=15): the control group, the electric shock group, the renal sympathetic excision group, and the Tempol electric shock group. The stress hormone corticosterone in the plasma of each group was measured. The content of norepinephrine, the stress hormone in the kidney, was used to determine the content of oxidative stress product TBARS in the plasma of rats in each group, and the activity of antioxidant enzyme SOD and GSH-Px in the plasma of each group. The thrombin analyzer was used to measure the time of prothrombin (prothrombin time, PT), and the time of active partial thromboplastin (activated partial prothrombi). N time, APPT) and thrombin time (thrombin time, TT). Platelet aggregation time under the stimulation of adenosine two phosphoric acid (ADP) and collagen (collagen) was measured respectively. The platelet aggregation rate was calculated. The deep vein thrombosis model was made by the ligation of the inferior vena cava and the thrombus was taken to determine the weight of thrombus. Results: 1. electric shock after two weeks in rats. The content of corticosterone and norepinephrine in the kidney increased significantly, the rats were in the stress state, the renal sympathetic nerve excision group and the Tempol group did not significantly increase the stress hormone in the rats with.2. and the control group. Compared with the control group, the content of TBARS in the plasma of the electric shock group was significantly increased, while the activity of SOD and GSH-Px in the plasma was significantly reduced. The oxidation / antioxidant system imbalance, oxidation level, renal sympathetic excision group, and Tempol electric shock group did not increase the oxidation level of rats with.3. and the control group. Compared with the control group, the TT of the rats in the electric shock group was significantly higher than that of the control group. Compared with the control group, the platelet aggregation rate under the stimulation of ADP and collagen in the electric shock group was significantly higher than that of the control group. The platelet aggregation rate under ADP and collagen stimulation did not increase significantly after renal sympathetic excision and antioxidant treatment. Compared with the control group, the weight of deep vein thrombosis in the electric shock group was significantly higher than that of the control group. The weight of the thrombus in the renal sympathetic excision group and the Tempol group did not increase significantly. Conclusion: the sympathetic nerve was not significantly increased. Conclusion: in the sympathetic nerve, the sympathetic nerve is not significantly increased. Conclusion: in the sympathetic nerve, the sympathetic nerve is not significantly increased. Conclusion: in the sympathetic nerve, the sympathetic nerve is not significantly increased. Conclusion: in the sympathetic nerve, the ADP Under the synergistic involvement of the system and oxidative stress, deep vein thrombosis is caused by plantar shock.

【學(xué)位授予單位】:蘇州大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號】:R544.1;R543.6

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5 李慶祥;高血壓及其靶器官損害的相關(guān)基因研究[D];中國協(xié)和醫(yī)科大學(xué);2003年

6 李岱;降鈣素基因相關(guān)肽與高血壓及吳茱萸次堿的治療作用[D];中南大學(xué);2008年

7 王文靖;血暢寧的抗高血壓及靶器官保護效應(yīng)的機制研究[D];廣州中醫(yī)藥大學(xué);2012年

8 施瀟瀟;腺苷1型受體在高血壓腎小管周毛細(xì)血管損傷中作用機制初探[D];北京協(xié)和醫(yī)學(xué)院;2014年

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10 李湘民;高血壓腦組織及血液中Klotho基因表達(dá)狀況的研究[D];中南大學(xué);2008年

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