【摘要】：目的:通過硝普鈉聯(lián)合艾司洛爾對大鼠進行不同程度的控制性降壓,觀察其對大鼠術(shù)后認(rèn)知功能的影響,并觀察其對大鼠海馬CA1區(qū)Aβ蛋白及tau蛋白磷酸化表達的影響。方法:本實驗包括兩部分內(nèi)容:(1)不同程度控制性降壓對大鼠術(shù)后認(rèn)知功能的影響。(2)不同程度控制性降壓對大鼠海馬CA1區(qū)Aβ蛋白及tau蛋白磷酸化表達的影響。選擇健康成年雄性SD大鼠96只,體重280~320g,采用隨機數(shù)字表法,將大鼠隨機分為4組,每組24只。正常對照組(C組):不做任何處理;控制性降壓Ⅰ組(CH1組):聯(lián)合應(yīng)用硝普鈉和艾司洛爾使MAP降壓基礎(chǔ)值的30%;控制性降壓Ⅱ組(CH2組):聯(lián)合應(yīng)用硝普鈉和艾司洛爾使MAP降壓基礎(chǔ)值的45%;控制性降壓Ⅲ組(CH3組):聯(lián)合應(yīng)用硝普鈉和艾司洛爾使MAP降壓基礎(chǔ)值的60%;并維持目標(biāo)血壓1h,所有大鼠降壓1h后均復(fù)壓,復(fù)壓時間為2h。術(shù)中嚴(yán)密監(jiān)測各組大鼠的各項血流動力學(xué)指標(biāo),并進行動脈血氣分析,分別于術(shù)前及術(shù)后對各組大鼠進行Morris水迷宮實驗測定認(rèn)知功能,于水迷宮測試結(jié)束后處死大鼠,取大鼠海馬組織,進行HE染色,光鏡下觀察大鼠海馬組織CA1區(qū)神經(jīng)元病理學(xué)結(jié)果,TUNEL法測定海馬神經(jīng)元凋亡情況,并采用Western blot法檢測海馬Aβ蛋白和磷酸化tau蛋白表達情況。結(jié)果:(1)與C組比較,CH2及CH3組大鼠術(shù)后逃避潛伏期均延長,穿越平臺次數(shù)均減少(P0.05),CH1組比較差異無統(tǒng)計學(xué)意義(P0.05);與CH1組比較,CH2及CH3組大鼠術(shù)后逃避潛伏期均延長,穿越平臺次數(shù)均減少(P0.05);與CH2組比較,CH3組大鼠術(shù)后逃避潛伏期延長,穿越平臺次數(shù)減少(P0.05);(2)HE染色:C組及CH1組大鼠海馬CA1區(qū)神經(jīng)元形態(tài)和結(jié)構(gòu)未見異常;CH2組海馬CA1區(qū)神經(jīng)元排列不規(guī)則,胞體縮小,細胞間隙欠清楚,神經(jīng)元數(shù)量輕度減少;CH3組CA1區(qū)神經(jīng)元細胞排列紊亂,出現(xiàn)大量凋亡細胞。(3)與C組比較,CH2及CH3組大鼠術(shù)后海馬Aβ蛋白和磷酸化tau蛋白表達均升高(P0.05),CH1組比較差異無統(tǒng)計學(xué)意義(P0.05);與CH1組比較,CH2及CH3組大鼠術(shù)后海馬Aβ蛋白和磷酸化tau蛋白表達均升高(P0.05);與CH2組比較,CH3組大鼠術(shù)后海馬Aβ蛋白和磷酸化tau蛋白表達升高(P0.05)。結(jié)論:1、控制性降壓達一定程度后可導(dǎo)致大鼠術(shù)后認(rèn)知功能障礙,并隨著降壓幅度的增加,術(shù)后認(rèn)知功能障礙加重。2、控制性降壓導(dǎo)致大鼠術(shù)后認(rèn)知功能障礙的機制可能與其上調(diào)海馬CA1區(qū)Aβ蛋白及磷酸化tau蛋白表達有關(guān)。
[Abstract]:Aim: to observe the effect of sodium nitroprusside combined with esmolol on postoperative cognitive function and phosphorylation of A 尾 protein and tau protein in CA1 region of rat hippocampus. Methods: this experiment includes two parts: (1) the effect of controlled hypotension on the cognitive function of rats after operation, (2) the effect of controlled hypotension on the expression of A 尾 protein and tau protein phosphorylation in CA1 region of rat hippocampus. 96 healthy adult male SD rats weighing 280 ~ 320g were randomly divided into 4 groups with 24 rats in each group. Normal control group (group C): no treatment; Controlled hypotension group I (CH1 group): combined use of sodium nitroprusside and esmolol to reduce MAP blood pressure base value 30; controlled hypotension group II (CH2 group): combined use of sodium nitroprusside and esmolol to make MAP base value 45; controlled hypotension group III (CH3) Group A: combined use of sodium nitroprusside and esmolol to reduce blood pressure by 60% of the baseline value of MAP and maintain the target blood pressure for 1 hour, and all rats were repressed after 1 hour of hypotension. The repressing time is 2 h. The hemodynamic indexes of each group were closely monitored during the operation, and arterial blood gas analysis was performed. The cognitive function of each group was measured by Morris water maze test before and after operation, and the rats were killed after the water maze test. The hippocampal tissues of rats were stained with HE, and the neuronal apoptosis in the CA1 area of hippocampus was observed by light microscopy. The expression of A 尾 protein and phosphorylated tau protein in hippocampus was detected by Western blot method, Tunel method was used to detect the apoptosis of hippocampal neurons. Results: (1) compared with group C and group C, the escape latency of rats in CH2 and CH3 groups were prolonged and the times of crossing platform were decreased (P0.05), there was no significant difference between CH1 group and group C (P0.05), and the escape latency of CH2 group and CH3 group were prolonged compared with that of group C (P0.05). Compared with CH2 group, the escape latency of CH3 group was longer than that of CH2 group. The number of crossing platform decreased (P0.05); (2) in group C and CH1, there was no abnormality in the morphology and structure of hippocampal CA1 neurons. In CH2 group, the hippocampal CA1 neurons arranged irregularly, the cell bodies were reduced, and the gap between neurons was not clear. The number of neurons decreased slightly in CH3 group, and the neuronal cells in the CA1 region of CH3 group were disordered. A large number of apoptotic cells appeared. (3) compared with group C and CH3 group, the expression of A 尾 protein and phosphorylated tau protein in hippocampus of rats in CH2 and CH3 groups increased significantly (P0.05), and there was no significant difference between CH1 group and CH1 group (P0.05), and the expression of A 尾 protein in hippocampus of CH2 and CH3 groups was higher than that of CH1 group (P0.05). Compared with CH2 group, the expression of hippocampal A 尾 protein and phosphorylated tau protein increased in CH3 group (P0.05). ConclusionThe controlled hypotension to a certain extent may lead to postoperative cognitive dysfunction in rats, and with the increase of the amplitude of hypotension, The mechanism of cognitive dysfunction induced by controlled hypotension may be related to the up-regulation of expression of A 尾 protein and phosphorylated tau protein in hippocampal CA1.
【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R614

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相關(guān)期刊論文 前1條

1 李靜;周華東;王延江;張猛;許志強;方傳勤;;腦缺血對阿爾茨海默病模型大鼠認(rèn)知功能的影響及其機制探討[J];中國神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2008年05期

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