心脏骤停PR-MODS兔动物模型的建立和生脉注射液干预治疗的实验研究

发布时间：2018-08-08 14:18

【摘要】： 复苏后多器官功能障碍综合征(post resuscitation multiple organ dysfunction syndrome,PR-MODS)是导致心脏骤停后最终复苏失败和整体预后不良的重要原因。PR-MODS确切的发生机制尚不十分清晰,特别是缺乏复苏后多器官功能障碍综合征相关动物模型,致使国内外心肺脑复苏的动物实验研究仍停留在心脏骤停的初级复苏阶段。本论文在建立窒息法致家兔心脏骤停及PR-MODS动物模型基础上,探讨了其可行性、发生机制以及生脉注射液早期干预治疗的影响。本论文主要调查ICU收治心脏骤停及PR-MODS患者的临床流行病学,并探讨和分析了心脏骤停PR-MODS相关影响因素。在实验研究中首先建立了窒息法致兔心脏骤停模型,观察了生脉注射液对模型自主循环恢复及血流动力学改变的影响;观察了ROSC后兔SIRS、TNF-a(ELISA法)、主要脏器功能指标以及病理学改变,探讨了建立PR-MODS模型的可行性;分别采用TUNEL法和免疫组织化学法检测了PR-MODS兔心肌细胞凋亡和Fas基因蛋白表达变化,同时观察生脉注射液干预后对上述指标的影响。研究结果显示:1、明确了ICU收治心脏骤停自主循环恢复患者中PR-MODS的发生和死亡率较高,与自主循环恢复时间密切相关,其预后可能受多种因素影响,强调应尽快恢复组织灌注和供氧,积极复苏后脏器支持治疗。2、首次采用窒息法建立心脏骤停PR-MODS动物模型,证明了兔心脏骤停ROSC后出现SIRS反应、TNF-a升高、主要脏器功能指标改变以及病理学超微结构上的变化,提示窒息法致兔心脏骤停PR-MODS动物模型的建立具有可行性,为后续研究窒息时间应选择为7分钟。3、证实了生脉注射液有利于缩短家兔自主循环恢复时间、可改善心脏骤停后左室舒缩功能,起到复苏后稳定血流动力学的作用。④证实了生脉注射液还可抑制兔复苏后TNF-a的变化,减轻PR-MODS兔主要器官受累程度,抑制心肌细胞凋亡和降低Fas蛋白表达,从而起到心肌保护作用。本论文研究结果为今后临床心肺复苏领域PR-MODS的防治研究创建了有价值的动物模型,同时也为中药防治PR-MODS提供了具有一定临床实用价值的理论依据。
[Abstract]:Post resuscitation multiple organ dysfunction syndrome (PR-MODS) after resuscitation is an important cause of the failure of final resuscitation and poor overall prognosis after cardiac arrest. The exact mechanism of.PR-MODS is not very clear, especially in the lack of animal models associated with multiple organ dysfunction syndrome after the Soviet Union. The experimental study of cardiopulmonary cerebral resuscitation at home and abroad still stays at the stage of primary resuscitation of cardiac arrest.
In this paper, on the basis of the establishment of asphyxia induced cardiac arrest and PR-MODS animal model, the feasibility, the mechanism and the effect of the early intervention treatment of Shengmai injection were discussed.
In this paper, we mainly investigated the clinical epidemiology of cardiac arrest and PR-MODS patients in ICU, and discussed and analyzed the PR-MODS related factors of cardiac arrest. In the experimental study, the model of cardiac arrest caused by asphyxia was first established, and the effects of Shengmai Injection on the recovery of autonomic circulation and hemodynamic changes of the model were observed. After ROSC SIRS, TNF-a (ELISA), main organ function index and pathological changes, the feasibility of establishing PR-MODS model was discussed. The apoptosis of myocardial cells of PR-MODS rabbit and the expression of Fas gene protein were detected by TUNEL and immunohistochemistry, and the effects of Shengmai Injection on the above indexes were observed.
The results show that: 1, it is clear that the occurrence and mortality of PR-MODS in the patients with cardiac arrest and spontaneous circulation recovery in ICU are closely related to the recovery time of autonomic circulation, and the prognosis may be affected by many factors. It is emphasized that the tissue perfusion and oxygen supply should be restored as soon as possible, and the post Soviet viscera support treatment.2 and the first use of asphyxia method to establish the heart. The PR-MODS animal model showed the SIRS reaction, the increase of TNF-a, the change of the main organ function index and the ultrastructure of the pathology after the sudden cardiac arrest of the rabbit heart, suggesting the feasibility of the establishment of the PR-MODS animal model of the cardiac arrest caused by the asphyxia method, and the 7 minute.3 should be selected for the subsequent asphyxiation time. Pulse injection can shorten the recovery time of autonomic circulation in rabbits, improve the function of left ventricular systolic and diastolic function after cardiac arrest and stabilize hemodynamics after resuscitation. (4) it is proved that Shengmai injection can also inhibit the changes of TNF-a after resuscitation, reduce the degree of main organ involvement in PR-MODS rabbits, inhibit apoptosis of myocardial cells and reduce the Fas protein table. The results of this paper have created a valuable animal model for the prevention and control of PR-MODS in the field of clinical cardiopulmonary resuscitation in the future, and also provide a theoretical basis for the prevention and control of PR-MODS in the prevention and treatment of Chinese medicine.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2009
【分类号】：R459.7;R-332;R285.5

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