慢性应激引发的高血压及深静脉血栓机制的研究

发布时间：2018-04-21 08:58

本文选题：肾交感神经 + 足底电击　；参考：《苏州大学》2015年硕士论文

【摘要】：第一部分:大鼠肾交感神经与肾素血管紧张素系统在慢性应激引发的高血压中的作用目的:在防治高血压病的研究中,科研人员发现长期慢性应激会严重影响患者的身心健康,使机体处于亚健康状态,乃至引发应激性高血压。研究证明,肾交感神经系统(RSNS)与肾素血管紧张素系统(RAS)在肾性高血压和自发性高血压的发病过程中起到了关键的作用,目前国内外关于应激性高血压发病机制的报道较少。本实验将致力于探究肾交感神经系统与肾素血管紧张素系统在应激性高血压中的作用机制。方法:我们将90只SD大鼠随机平均分为6组(n=15):①空白对照组,②长期慢性足底电击组(电击组),③肾交感神经切除组,④肾交感神经切除+长期慢性电击组(肾交感神经切除电击组),⑤加血管紧张素转换酶1抑制剂(卡托普利)+长期慢性电击组(卡托普利电击组),⑥加抗氧化剂-4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基(superoxide dismutase mimetic,Tempol)+长期慢性电击组(Tempol电击组)。对电击组大鼠进行足底电击14天。测定大鼠的血压。测定各组大鼠血浆中应激激素皮质酮(corticosterone)和肾脏中应激激素去甲肾上腺素(noradrenaline,NE)的含量。测定各组大鼠外周RAS水平的变化,即测定血浆中肾素(renin),血管紧张素II(angiotensin II,Ang II)的含量。测定各组大鼠中枢RAS水平的变化,即分别对大脑皮层和下丘脑中RAS中的成员进行转录和翻译水平的分析。测定各组大鼠血浆中氧化应激产物硫代巴比妥酸反应物(thiobarbituric acid reactive substances,TBARS)的含量。测定各组大鼠血浆中抗氧化酶超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的活性。结果:1.与对照组大鼠相比,电击组大鼠血压出现显著性升高,肾交感神经切除电击组,加卡托普利电击组以及加Tempol电击组大鼠的血压均未出现显著升高。2.电击两周后大鼠血浆中皮质酮,肾脏中去甲肾上腺素含量显著升高,大鼠处于应激状态,肾交感神经切除电击组,加卡托普利电击组以及加Tempol电击组大鼠应激激素均未显著性升高。3.与对照组相比,电击组大鼠血浆中肾素,Ang II的浓度显著升高,肾交感神经切除电击组,加卡托普利电击组以及加Tempol电击组大鼠的血压均未显著升高。4.与对照组相比,电击组大鼠大脑皮层及下丘脑中血管紧张素原(angiotensinogen,AGT),血管紧张素转换酶1(angiotensin converting enzyme 1,ACE1),血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2),血管紧张素受体1a(angiotensin II receptor 1a,AT1a)的信使RNA(m RNA)表达量与蛋白质表达量均显著升高,数据显示,交感神经切除处理与抗氧化处理后,无论是在外周还是中枢,大鼠肾素血管紧张素系统均受到了显著的抑制。5.与对照组相比,大鼠血浆中TBARS的含量显著升高,而血浆中SOD,GSH-Px的活性显著降低,大鼠的氧化/抗氧化系统失衡,氧化水平升高,肾交感神经切除电击组,加卡托普利电击组以及加Tempol电击组大鼠的氧化水平未见升高。结论:肾交感神经系统,肾素血管紧张素系统与氧化应激在慢性应激诱导的高血压的发生过程中起着重要作用;肾素血管紧张素系统,肾交感神经系统与氧化应激这三者相互影响并共同参与慢性应激诱导的高血压的发生。第二部分:大鼠肾交感神经与氧化应激在慢性应激引发的深静脉血栓中的作用目的:深静脉血栓(deep vein thrombosis of lower extremity,DVT)是指血液在深静脉腔内非正常凝结,是心血管疾病中的常见病、多发病,在我国DVT的患病率以及确诊率近年来呈现出逐年递增的趋势,因此探讨其发病原因,对DVT的预防和治疗有着重要意义。本实验将致力于探究慢性应激诱导的DVT中的发病机制。方法:我们将60只SD大鼠随机平均分为4组(n=15):对照组,电击组,肾交感神经切除电击组,加Tempol电击组。测定各组大鼠血浆中应激激素皮质酮和肾脏中应激激素去甲肾上腺素的含量。测定各组大鼠血浆中氧化应激产物TBARS的含量;测定各组大鼠血浆中抗氧化酶SOD和GSH-Px的活性。使用凝血分析仪测量凝血酶原时间(prothrombin time,PT),活化部分凝血活酶时间(activated partial prothrombin time,APPT)和凝血酶时间(thrombin time,TT)。使用血小板聚集仪分别测量腺苷二磷酸(ADP)和胶原蛋白(collagen)刺激下的血小板聚集时间,计算血小板聚集率。下腔静脉结扎法制造深静脉血栓模型,取血栓测定血栓的重量。结果:1.电击两周后大鼠血浆中皮质酮,肾脏中去甲肾上腺素含量显著升高,大鼠处于应激状态,肾交感神经切除电击组,以及加Tempol电击组大鼠应激激素均未显著性升高。2.与对照组相比,电击组大鼠血浆中TBARS的含量显著升高,而血浆中SOD,GSH-Px的活性显著降低,大鼠的氧化/抗氧化系统失衡,氧化水平升高,肾交感神经切除电击组,以及加Tempol电击组大鼠氧化水平未见升高。3.与对照组相比,电击组大鼠的TT显著升高。4.与对照组相比,电击组大鼠在ADP和collagen刺激下的血小板聚集率显著升高,肾交感神经切除处理与抗氧化处理后,ADP和collagen刺激下的血小板聚集率未出现显著升高。5.与对照组相比,电击组大鼠深静脉血栓的重量显著升高,肾交感神经切除电击组以及加Tempol电击组血栓的重量未见显著升高。结论:在交感神经系统和氧化应激的协同参与下,足底电击引发深静脉血栓。
[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.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R544.1;R543.6

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