论文部分内容阅读
目的:探讨中枢胆碱酯酶抑制剂加兰他敏对失血性休克大鼠的保护作用及其作用机制。方法:采用股动脉间断放血法制备失血性休克动物的模型。60只成年SD大鼠随机分为假休克(假Hem)组、休克(Hem)组、加兰他敏(Gal)组,迷走神经切断(Vgx)组、硫酸阿托品(AS)组、α-银环蛇毒素(α-BGT)组,每组10只。各组动物均行右侧股动脉置管并连续监测平均动脉压(MAP),模型稳定后20min取动脉血标本,进行血浆肿瘤坏死因子-α(TNF-α)、血气及乳酸值检测;处死动物取肺脏和肝脏标本行病理学观察。另取40只大鼠随机分成假休克、休克、加兰他敏和迷走神经切断4组,仅观察生存状况而不作其他干预,观察时间为180min。结果:与假Hem组比较,Hem组平均生存时间显著缩短,各时间点的生存率均显著降低(均为P<0.05),MAP值持续低下,血浆TNF-α浓度显著升高,并有严重代谢性酸中毒和高乳酸血症,同时肺脏和肝脏明显炎性病理学改变;与Hem组比较,Gal组平均生存时间延长,各时间点生存率均显著提高(均为P<0.05),MAP值呈升高趋势,血浆TNF-α浓度降低,代谢性酸中毒缓解,肺脏和肝脏的炎症明显改善。经迷走神经切断、硫酸阿托品及α-BGT拮抗后,加兰他敏的上述效应则完全抵消。结论:加兰他敏通过激活中枢M受体,对失血性休克大鼠发挥抗炎抗休克保护作用,该效应可能与激活胆碱能抗炎通路有关。
Objective: To investigate the protective effect of central cholinesterase inhibitor galantamine on hemorrhagic shock in rats and its mechanism. Methods: The animal model of hemorrhagic shock was prepared by intermittent perfusion method of femoral artery. Sixty adult SD rats were randomly divided into sham-shock group, Hem group, Gal group, Vgx group, AS group, Snake toxin (α-BGT) group, 10 rats in each group. The animals in each group were placed on the right femoral artery and the mean arterial pressure (MAP) was continuously monitored. The blood samples were collected 20 minutes after the model was stabilized and the plasma levels of tumor necrosis factor-α (TNF-α), blood gas and lactate were measured. Pathological observation of lung and liver specimens from animals. Another 40 rats were randomly divided into sham shock, shock, galantamine and vagotomy 4 groups, only to observe the living conditions without any other intervention, the observation time was 180min. Results: Compared with the Hem group, the average survival time of Hem group was significantly shortened, the survival rates of each group were significantly decreased (all P <0.05), the MAP value was continuously decreased, the plasma TNF-α concentration was significantly increased Metabolic acidosis and hyperlipidemia, meanwhile lung and liver were significantly changed in inflammatory pathology. Compared with Hem group, the mean survival time in Gal group was prolonged and the survival rate was significantly increased at each time point (both P <0.05) Increasing trend, plasma TNF-α concentration decreased, metabolic acidosis alleviated, lung and liver inflammation improved significantly. After vagotomy, atropine sulfate and α-BGT antagonism, galantamine above effect is completely offset. CONCLUSION: Galantamine exerts anti-inflammatory and anti-shock protective effect on hemorrhagic shock rats by activating central M receptor, which may be related to the activation of cholinergic anti-inflammatory pathway.