本文選題：曲馬朵 + 東莨菪堿�。� 參考：《河北醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:近年來,隨著麻醉技術(shù)的不斷進步、新型麻醉藥的推陳出新以及監(jiān)測手段的不斷完善,使得麻醉死亡率大大降低,臨床麻醉關(guān)注的重點已經(jīng)轉(zhuǎn)向如何減少心臟、大腦等全身各臟器并發(fā)癥的發(fā)生率。隨著我國步入老齡化社會階段,接受重大手術(shù)的老年患者日益增多,術(shù)后老年人極易出現(xiàn)精神功能障礙,表現(xiàn)為中風(fēng)(1.5~5.2%)、譫妄(10~30%)、短期的(33~83%)及長期的(20~60%)認知功能障礙等[1]。其中術(shù)后認知功能障礙(Postoperative Cognitive Dysfunction,POCD)因其發(fā)病率高,對患者愈后危害大而備受關(guān)注,國內(nèi)外學(xué)者也針對其做了大量研究,但POCD的發(fā)病機制尚不清楚,故臨床缺少有效的防治方法。隨著神經(jīng)生物學(xué)研究的進展,目前的觀點認為,中樞膽堿能系統(tǒng)的主要遞質(zhì)乙酰膽堿的生理功能主要與學(xué)習(xí)、記憶、鎮(zhèn)痛、睡眠、感覺和運動有關(guān),而參與精神、情緒活動的中樞遞質(zhì)主要以分布于中央灰質(zhì)、下丘腦及邊緣皮質(zhì)系統(tǒng)的單胺類遞質(zhì)為主,包括多巴胺(Dopamine,DA)、5-羥色胺(5-hydroxy tryptamine,5-HT)及去甲腎上腺素(Norepinephrine,NE)[2]。國內(nèi)外關(guān)于不同原因引起的POCD與各種單胺類遞質(zhì)的關(guān)系已有報道。因此,本研究擬采用東莨菪堿致大鼠認知功能障礙模型,進一步觀察腹腔注射5-HT重攝取抑制劑曲馬多對大鼠認知功能障礙的預(yù)防作用,以探討POCD可能的發(fā)病機制。方法:1健康2月齡雄性SD大鼠40只,體重130~150g,采用隨機數(shù)字表法,將其分為4組(n=10):鹽水對照組(C組)、東莨菪堿組(S組)、單純曲馬多組(T組)和曲馬多干預(yù)組(S+T組)。S組采用腹腔注射東莨菪堿1.8mg/kg。C組和T組分別腹腔注射等容量生理鹽水或曲馬多10mg/kg,S+T組同時腹腔注射東莨菪堿1.8mg/kg和曲馬多10mg/kg。2 4組大鼠注射藥物后即刻放入自制曠場實驗箱,觀察大鼠腹腔內(nèi)注射藥物前10min及注射后1h內(nèi)大鼠的情緒及行為學(xué)變化。分別記錄各時間段內(nèi)(T0-T6)大鼠周邊跑格數(shù),垂直運動次數(shù),記錄中央格停留時間、中央跑格數(shù)、修飾次數(shù)、修飾時間。3 4組大鼠注射藥物7d后行Y型迷宮實驗測試認知功能,記錄全天訓(xùn)練總次數(shù)和達標時間。4 Y型迷宮實驗后腹腔注射水合氯醛350 mg/kg麻醉大鼠,眼角取血2ml,斷頭處死,取雙側(cè)海馬神經(jīng)元。5光鏡下觀察大鼠海馬組織HE染色切片,了解海馬神經(jīng)元細胞的形態(tài)學(xué)變化。6采用ELISA法分別檢測大鼠血清和海馬組織中5-HT的水平。7所得數(shù)據(jù)采用SPSS17.0軟件進行統(tǒng)計學(xué)分析,計量資料以均數(shù)±標準差(sx±)表示,重復(fù)測量資料采用重復(fù)測量設(shè)計的方差分析,隨機區(qū)組資料采用單因素方差分析,計數(shù)資料采用SNK檢驗,P0.05為差異有統(tǒng)計學(xué)意義。結(jié)果:1光鏡下,C組與T組大鼠海馬神經(jīng)元細胞排列整齊,層次清晰,核大而圓,形態(tài)完整。S組大鼠海馬神經(jīng)元細胞排列紊亂,層次不清,出現(xiàn)細胞膜斷裂,細胞質(zhì)減少,細胞核固縮,甚至空泡變性。S+T組大鼠海馬神經(jīng)元細胞上述形態(tài)學(xué)改變較S組明顯減輕。2與C組比較,S組曠場試驗各時間段內(nèi)大鼠周邊跑格數(shù)、垂直運動次數(shù)和中央格跑格數(shù)增多,中央格停留時間延長,修飾次數(shù)減少,在T1、T2和T6時間段內(nèi)修飾時間縮短,Y型迷宮實驗全天訓(xùn)練總次數(shù)和達標時間增加,大鼠血清和海馬組織中5-HT的水平下降(P0.05);S+T組曠場試驗各時間段內(nèi)大鼠周邊跑格數(shù)、垂直運動次數(shù)、中央格停留時間、修飾次數(shù)及修飾時間差異均無統(tǒng)計學(xué)意義(P0.05),Y型迷宮實驗全天訓(xùn)練總次數(shù)和達標反應(yīng)時間增加,大鼠血清和海馬組織中5-HT的水平下降(P0.05);T組大鼠血清和海馬組織中5-HT的水平升高(P0.05)。與S組比較,S+T組曠場試驗各時間段內(nèi)大鼠周邊跑格數(shù)、垂直運動次數(shù)和中央格跑格數(shù)減少,中央格停留時間縮短,修飾次數(shù)增多,在T1時間段內(nèi)修飾時間延長,Y型迷宮實驗全天訓(xùn)練總次數(shù)和達標反應(yīng)時間減少,大鼠血清和海馬組織中5-HT的水平升高(P0.05)。C組與T組間大鼠上述各項認知功能指標差異無統(tǒng)計學(xué)意義(P0.05)。結(jié)論:腹腔注射曲馬多10mg/kg可減輕東莨菪堿所致大鼠的認知功能障礙的表現(xiàn),使大鼠海馬神經(jīng)元細胞形態(tài)學(xué)改變減輕,海馬組織和血清中5-HT水平升高。提示東莨菪堿致所致認知功能障礙的機制可能與大鼠體內(nèi)乙酰膽堿及5-HT這兩種神經(jīng)遞質(zhì)之間的均衡性失調(diào)有關(guān)。
[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.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R614

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