曲马多对东莨菪碱致大鼠认知功能障碍的影响

发布时间：2018-06-28 14:30

本文选题：曲马朵 + 东莨菪碱　；参考：《河北医科大学》2015年硕士论文

【摘要】：目的:近年来,随着麻醉技术的不断进步、新型麻醉药的推陈出新以及监测手段的不断完善,使得麻醉死亡率大大降低,临床麻醉关注的重点已经转向如何减少心脏、大脑等全身各脏器并发症的发生率。随着我国步入老龄化社会阶段,接受重大手术的老年患者日益增多,术后老年人极易出现精神功能障碍,表现为中风(1.5~5.2%)、谵妄(10~30%)、短期的(33~83%)及长期的(20~60%)认知功能障碍等[1]。其中术后认知功能障碍(Postoperative Cognitive Dysfunction,POCD)因其发病率高,对患者愈后危害大而备受关注,国内外学者也针对其做了大量研究,但POCD的发病机制尚不清楚,故临床缺少有效的防治方法。随着神经生物学研究的进展,目前的观点认为,中枢胆碱能系统的主要递质乙酰胆碱的生理功能主要与学习、记忆、镇痛、睡眠、感觉和运动有关,而参与精神、情绪活动的中枢递质主要以分布于中央灰质、下丘脑及边缘皮质系统的单胺类递质为主,包括多巴胺(Dopamine,DA)、5-羟色胺(5-hydroxy tryptamine,5-HT)及去甲肾上腺素(Norepinephrine,NE)[2]。国内外关于不同原因引起的POCD与各种单胺类递质的关系已有报道。因此,本研究拟采用东莨菪碱致大鼠认知功能障碍模型,进一步观察腹腔注射5-HT重摄取抑制剂曲马多对大鼠认知功能障碍的预防作用,以探讨POCD可能的发病机制。方法:1健康2月龄雄性SD大鼠40只,体重130~150g,采用随机数字表法,将其分为4组(n=10):盐水对照组(C组)、东莨菪碱组(S组)、单纯曲马多组(T组)和曲马多干预组(S+T组)。S组采用腹腔注射东莨菪碱1.8mg/kg。C组和T组分别腹腔注射等容量生理盐水或曲马多10mg/kg,S+T组同时腹腔注射东莨菪碱1.8mg/kg和曲马多10mg/kg。2 4组大鼠注射药物后即刻放入自制旷场实验箱,观察大鼠腹腔内注射药物前10min及注射后1h内大鼠的情绪及行为学变化。分别记录各时间段内(T0-T6)大鼠周边跑格数,垂直运动次数,记录中央格停留时间、中央跑格数、修饰次数、修饰时间。3 4组大鼠注射药物7d后行Y型迷宫实验测试认知功能,记录全天训练总次数和达标时间。4 Y型迷宫实验后腹腔注射水合氯醛350 mg/kg麻醉大鼠,眼角取血2ml,断头处死,取双侧海马神经元。5光镜下观察大鼠海马组织HE染色切片,了解海马神经元细胞的形态学变化。6采用ELISA法分别检测大鼠血清和海马组织中5-HT的水平。7所得数据采用SPSS17.0软件进行统计学分析,计量资料以均数±标准差(sx±)表示,重复测量资料采用重复测量设计的方差分析,随机区组资料采用单因素方差分析,计数资料采用SNK检验,P0.05为差异有统计学意义。结果:1光镜下,C组与T组大鼠海马神经元细胞排列整齐,层次清晰,核大而圆,形态完整。S组大鼠海马神经元细胞排列紊乱,层次不清,出现细胞膜断裂,细胞质减少,细胞核固缩,甚至空泡变性。S+T组大鼠海马神经元细胞上述形态学改变较S组明显减轻。2与C组比较,S组旷场试验各时间段内大鼠周边跑格数、垂直运动次数和中央格跑格数增多,中央格停留时间延长,修饰次数减少,在T1、T2和T6时间段内修饰时间缩短,Y型迷宫实验全天训练总次数和达标时间增加,大鼠血清和海马组织中5-HT的水平下降(P0.05);S+T组旷场试验各时间段内大鼠周边跑格数、垂直运动次数、中央格停留时间、修饰次数及修饰时间差异均无统计学意义(P0.05),Y型迷宫实验全天训练总次数和达标反应时间增加,大鼠血清和海马组织中5-HT的水平下降(P0.05);T组大鼠血清和海马组织中5-HT的水平升高(P0.05)。与S组比较,S+T组旷场试验各时间段内大鼠周边跑格数、垂直运动次数和中央格跑格数减少,中央格停留时间缩短,修饰次数增多,在T1时间段内修饰时间延长,Y型迷宫实验全天训练总次数和达标反应时间减少,大鼠血清和海马组织中5-HT的水平升高(P0.05)。C组与T组间大鼠上述各项认知功能指标差异无统计学意义(P0.05)。结论:腹腔注射曲马多10mg/kg可减轻东莨菪碱所致大鼠的认知功能障碍的表现,使大鼠海马神经元细胞形态学改变减轻,海马组织和血清中5-HT水平升高。提示东莨菪碱致所致认知功能障碍的机制可能与大鼠体内乙酰胆碱及5-HT这两种神经递质之间的均衡性失调有关。
[Abstract]:Objective: in recent years, with the continuous progress of anesthesia technology, new anesthetics and continuous improvement of monitoring methods, the death rate of anesthesiology has been greatly reduced. The focus of attention on clinical anesthesia has turned to reduce the incidence of complications of all organs such as the heart and the whole body. There is a growing number of elderly patients with major surgery, and the elderly people are extremely prone to mental dysfunction after operation, including 1.5~5.2%, 10~30%, short-term (33~83%) and long-term (20~60%) cognitive dysfunction, including Postoperative Cognitive Dysfunction (POCD) because of its high incidence, and the more critical to the patients. Many scholars at home and abroad have done a lot of research, but the pathogenesis of POCD is still not clear, so the clinical lack of effective prevention and control methods. With the progress of neurobiology research, the main physiological function of the main neurotransmitter acetylcholine in the central cholinergic system is learning, memory, analgesia, sleep, and the main function of the central cholinergic system. Sensation is associated with exercise, and the central transmitters involved in the spirit and emotional activity are mainly distributed in the central gray matter, the hypothalamus and the marginal cortex of the monoamine transmitters, including dopamine (Dopamine, DA), 5- serotonin (5-hydroxy tryptamine, 5-HT) and Norepinephrine, NE (NE) [2]. at home and abroad on different causes of P The relationship between OCD and a variety of monoamine transmitters has been reported. Therefore, this study intends to use the model of scopolamine induced cognitive dysfunction to further observe the preventive effect of intraperitoneal injection of 5-HT reuptake inhibitor tramadol on cognitive impairment in rats, in order to explore the possible pathogenesis of POCD. Methods: 1 healthy 2 month old male SD rats. Weight 130~150g was divided into 4 groups (n=10): saline control group (group C), scopolamine group (group S), simple tramadol group (group T) and tramadol group (group S+T),.S group was injected intraperitoneally with scopolamine group 1.8mg/kg.C and T group, respectively, with abdominal cavity injection of equal volume physiological saline or tramadol 10mg/kg, S+T group was injected simultaneously intraperitoneally. After injection of scopolamine 1.8mg/kg and tramadol 10mg/kg.2 4 rats, the rats were injected into the self-made open field test box immediately to observe the emotional and behavioral changes in the rat intraperitoneal injection of 10min before and after the injection of 1H. The number of peripheral running cases, the frequency of vertical movement and the residence time of the central lattice were recorded respectively in the rats of each time period (T0-T6). The central running number, the times of modification, the time of modification,.3 4 groups of rats were injected with the drug 7d to test the cognitive function of the Y labyrinth test. The total number of training times and the time of the standard time of the.4 Y maze test were recorded in the 350 mg/kg anesthetized rats with chloral chloral hydrate, the eyes were taken blood 2ml, and the head was killed, and the hippocampus neuron.5 light microscope was used to observe the hippocampus of the rat hippocampus. The morphological changes of hippocampal neurons were studied by tissue HE staining..6 was used to detect the level of 5-HT in the serum and hippocampus of rats by ELISA method, and the data were analyzed by SPSS17.0 software. The measurement data were expressed with the mean number of standard deviation (SX +), and the repeated measurement data were analyzed by the repeated measurement design of variance analysis. The data of the machine area group were analyzed by single factor variance, the count data were tested by SNK test, and the difference of P0.05 was statistically significant. Results: under 1 light microscope, the hippocampal neurons in group C and T were arranged neatly, the layers were clear, the nucleus was large and round, the hippocampal neurons in the.S group were in disorder, the layers were not clear, cell membrane breakage was found. The morphological changes of hippocampal neurons in the.S+T group were significantly lower than that of the S group. Compared with the group of C, the peripheral running number of rats in the S group, the number of vertical movement and the number of central lattice running lattices increased, the time of the central lattice was prolonged, the number of modification decreased, and the time of T1, T2 and T6 in the T1, T2 and T6 time. The total time of modification in the Y labyrinth experiment increased and the level of 5-HT in the rats' serum and hippocampus decreased (P0.05). The number of peripheral running cases, the number of vertical movement, the residence time of the central lattice, the number of modification and the time of modification were not statistically significant (P0.05). The total number of times of total training and the time of the response to the standard increased, the level of 5-HT in the serum and hippocampus of the rats decreased (P0.05), and the level of 5-HT in the serum and hippocampal tissues of the T group increased (P0.05). Compared with the S group, the number of circumferential running lattices, the number of vertical movement and the number of the central lattice were reduced in the group S+T open field test in each time period. The retention time of the central lattice was shortened, the number of modification was increased, the time of modification was prolonged in the T1 time period. The total number of total training times and the time of standard response decreased in the Y labyrinth experiment. The level of 5-HT in the serum and hippocampus of rats increased (P0.05) and there was no statistical difference between the.C group and the T group (P0.05). The injection of tramadol 10mg/kg can reduce the cognitive impairment in rats induced by scopolamine, reduce the morphological changes of hippocampal neurons in rats and increase the level of 5-HT in the hippocampus and serum. The mechanism of cognitive impairment induced by scopolamine may be related to the two neurotransmitters of acetylcholine and 5-HT in rats. The imbalance of the balance between them.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R614

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