本文選題：利多卡因 + 術(shù)后認(rèn)知功能障礙�。� 參考：《中國人民解放軍醫(yī)學(xué)院》2014年博士論文

【摘要】：第一部分不同劑量利多卡因?qū)夏甏笫驪OCD行為學(xué)影響 目的：通過脾切除構(gòu)建老年大鼠術(shù)后認(rèn)知功能障礙（POCD）模型，探索老年大鼠POCD模型形成及維持時間，并以局部麻醉藥利多卡因作為研究工具，，研究利多卡因?qū)W(xué)習(xí)記憶功能損傷的改善作用，確定利多卡因改善POCD的最佳劑量。 方法：將50只老年SD大鼠，使用CHISS統(tǒng)計學(xué)軟件隨機分成5組，組別分別為：對照組、POCD模型組、利多卡因1組（1mg/kg/h）、利多卡因2組（2mg/kg/h）、利多卡因3組（4mg/kg/h）,每組10只。進(jìn)行連續(xù)5天的空間獲得性實驗后，第6天對各組老年SD大鼠進(jìn)行模型構(gòu)建和利多卡因干預(yù)。所有老年SD大鼠均在術(shù)后第1、3、7、14天利用Morris水迷宮對老年大鼠的空間記憶能力進(jìn)行測試。 結(jié)果：空間獲得性實驗會使老年大鼠的學(xué)習(xí)記憶能力隨著時間的延長而逐漸提高（P 0.01）、并在第5天趨于穩(wěn)定，且每天各組之間的沒有明顯差異。參考記憶的測試結(jié)果顯示，與對照組相比，POCD模型組和利多卡因3組（4mg/kg/h）的參考記憶能力明顯降低（P 0.05）;與POCD模型組相比，利多卡因1組（1mg/kg/h）和利多卡因3組（4mg/kg/h）的參考記憶能力明顯增強（P 0.05）。 工作記憶的測試結(jié)果顯示，與對照組相比，POCD模型組、利多卡因1組（1mg/kg/h）術(shù)后第1、3天，利多卡因3組（4mg/kg/h）術(shù)后第1、3、7天的工作記憶能力有顯著差異（P 0.05）;與POCD模型組比較，利多卡因1、2組（1、2mg/kg/h）的術(shù)后第1、3天和利多卡因3組（4mg/kg/h）的術(shù)后第1天的工作記憶能力有顯著差異（P0.05）。 結(jié)論：麻醉狀態(tài)下脾切除能夠成功建立POCD模型，且空間記憶能力的損害在術(shù)后第3天最明顯，術(shù)后第7天基本恢復(fù)正常，而圍術(shù)期尾靜脈持續(xù)泵注1h的1mg/kg/h利多卡因?qū)?gòu)建POCD模型后的老年大鼠空間記憶能力的改善作用最明顯，被確定為最佳治療劑量。 第二部分最佳劑量利多卡因?qū)OCD老年大鼠海馬組織和外周血炎癥反應(yīng)的影響 目的：通過分子生物學(xué)和免疫組織化學(xué)技術(shù)，觀察最佳劑量利多卡因?qū)OCD老年大鼠海馬和外周血炎癥反應(yīng)的影響，探索中樞和外周炎癥反應(yīng)與海馬星形膠質(zhì)細(xì)胞激活和表達(dá)變化的機制。 方法：確定量效關(guān)系和利多卡因的最佳劑量后，將72只老年SD大鼠，使用CHISS統(tǒng)計學(xué)軟件隨機分成3組，組別分別為：對照組、POCD模型組、利多卡因組（1mg/kg/h）。使用54只進(jìn)行Morris水迷宮實驗，每組18只，進(jìn)行連續(xù)5天的空間獲得性實驗后，第6天對各組老年SD大鼠進(jìn)行模型構(gòu)建和利多卡因干預(yù)，術(shù)后第1、3、7天對老年大鼠的空間記憶能力進(jìn)行測試。使用18只進(jìn)行新物體識別實驗，每組6只，術(shù)后第1天對老年大鼠的非空間記憶能力進(jìn)行測試。所有老年大鼠均在術(shù)后第1、3、7天取材，采用ELISA的方法對老年大鼠海馬組織和外周血漿炎癥細(xì)胞因子進(jìn)行檢測，采用組織免疫熒光染色和蛋白免疫印跡的方法觀察老年SD大鼠海馬組織中星形膠質(zhì)細(xì)胞激活和GFAP表達(dá)的情況。結(jié)果：確定利多卡因的最佳治療劑量為1mg/kg/h后，不僅使用Morris水迷宮實驗評價老年大鼠的空間記憶能力，還用新物體識別實驗評價非空間記憶能力，其結(jié)果顯示，與對照組相比，POCD模型組老年大鼠識別指數(shù)有顯著差異（P 0.05）；與POCD模型組對比，利多卡因組（1mg/kg/h）老年大鼠新物體識別指數(shù)有顯著差異（P 0.05）。 測定炎癥細(xì)胞因子結(jié)果顯示，關(guān)于促炎因子，與對照組相比，POCD模型組術(shù)后第1天和第3天老年大鼠海馬和血漿中的TNF-α、IL-1β和IL-6濃度分別有顯著差異（P 0.05）；與POCD模型組相比，1mg/kg/h利多卡因干預(yù)后，術(shù)后第1天和第3天老年大鼠海馬和血漿中的TNF-α、IL-1β和IL-6濃度分別有顯著差異（P 0.05）。而抗炎因子IL-10，與對照組相比，POCD模型組在術(shù)后第1、3天的海馬和血漿中的IL-10濃度分別有顯著差異（P 0.05）；與POCD模型組相比，利多卡因組（1mg/kg/h）術(shù)后第3天海馬和血漿中的IL-10濃度有顯著差異（P 0.05）。 組織免疫熒光染色法和蛋白免疫印跡法測定老年大鼠海馬組織星形膠質(zhì)細(xì)胞標(biāo)志物GFAP的結(jié)果顯示，與對照組相比，POCD模型組術(shù)后第1天和第3天海馬組織中GFAP的表達(dá)有顯著差異（P 0.05），且GFAP免疫熒光強度增加；與POCD模型組相比，利多卡因組（1mg/kg/h）術(shù)后第3天海馬組織中GFAP的表達(dá)有顯著差異（P 0.05），且GFAP免疫熒光強度顯著減弱。結(jié)論：圍術(shù)期尾靜脈持續(xù)泵注1h的1mg/kg/h利多卡因?qū)?gòu)建POCD模型后的老年大鼠空間記憶能力和非空間記憶能力均具有明顯的改善作用，也能夠很好地控制老年大鼠海馬和血漿中炎癥細(xì)胞因子（包括促炎因子和抗炎因子）的產(chǎn)生。應(yīng)用1mg/kg/h利多卡因，能夠明顯減弱老年大鼠在術(shù)后第1天和第3天海馬組織中星形膠質(zhì)細(xì)胞的激活和星形膠質(zhì)細(xì)胞特異性標(biāo)志物GFAP的表達(dá)。
[Abstract]:Effects of different doses of lidocaine on the behavior of POCD in aged rats

Objective : To establish a model of cognitive impairment ( POCD ) in aged rats by splenic resection , to explore the formation and maintenance time of POCD in aged rats , and to study the effect of lidocaine on learning and memory impairment by using lidocaine as the research tool , and to determine the optimal dose of lidocaine for improving POCD .

Methods : 50 old SD rats were randomly divided into 5 groups using CHISS statistical software . The rats were randomly divided into five groups : control group , POCD model group , lidocaine group 1 group ( 1mg / kg / h ) , lidocaine group 2 ( 2mg / kg / h ) and lidocaine 3 group ( 4mg / kg / h ) . All the old SD rats were tested on the 1st , 3rd , 7th and 14th days after operation .

Results : The results showed that the learning and memory ability of aged rats gradually increased with time ( P 0.01 ) , and there was no significant difference between groups on Day 5 . The reference memory capacity of POCD model group and lidocaine group 3 group ( 4mg / kg / h ) was significantly lower than that in control group ( P 0.05 ) . Compared with control group , the reference memory ability of the group of lidocaine group 1 ( 1mg / kg / h ) and lidocaine group 3 ( 4mg / kg / h ) was significantly increased ( P 0.05 ) .

The results of working memory showed that compared with the control group , there was a significant difference in the working memory ability of the POCD model group , the lidocaine group 1 group ( 1 mg / kg / h ) on the first , 3 and 7 days after the operation ( P 0.05 ) . Compared with the POCD model group , there was a significant difference in the working memory capacity ( P0.05 ) in the first , 3 and 3 days after the operation of the lidocaine 1,2 group ( 1 , 2 mg / kg / h ) and the first day after the operation of the lidocaine group 3 ( 4mg / kg / h ) .

Conclusion : The POCD model can be successfully established under the anesthesia state , and the damage of spatial memory ability is the most obvious at the third day of operation , the 7th day after the operation is basically normal , and the effect of 1 mg / kg / h lidocaine on the space memory ability of the old rats after the perioperative tail vein continuous pumping is the most obvious and is determined as the optimal therapeutic dose .

Effect of the second part of optimal dose lidocaine on the inflammatory response of hippocampus and peripheral blood in aged rats with POCD

Objective : To investigate the effects of lidocaine on inflammatory responses in hippocampus and peripheral blood of elderly rats with POCD by molecular biology and immunohistochemical technique .

Methods : 72 old SD rats were randomly divided into three groups : control group , POCD model group , lidocaine group ( 1mg / kg / h ) .
Compared with POCD model group , there was a significant difference in the identification index of new objects in the aged rats ( 1mg / kg / h ) ( P 0.05 ) .

The results showed that the levels of TNF - 偽 , IL - 1尾 and IL - 6 in the hippocampus and plasma of the aged rats were significantly higher than those in the control group ( P 0.05 ) .
Compared with the POCD model group , the levels of TNF - 偽 , IL - 1尾 and IL - 6 in the hippocampus and plasma of the aged rats were significantly different after the intervention of 1 mg / kg / h lidocaine ( P 0.05 ) . Compared with the control group , the levels of IL - 10 in the hippocampus and plasma of POCD model group were significantly higher than those in control group ( P 0.05 ) .
Compared with POCD model group , the concentration of IL - 10 in hippocampus and plasma of lidocaine group ( 1 mg / kg / h ) was significantly different ( P 0.05 ) .

The expression of GFAP in hippocampus of aged rats was significantly higher than that in control group ( P 0.05 ) , and GFAP immunofluoresence intensity increased .
Conclusion : The effect of 1 mg / kg / h lidocaine on the spatial memory and non - spatial memory in the hippocampus and plasma of aged rats was significantly improved compared with the POCD model group ( P 0.05 ) . Conclusion : The effect of 1 mg / kg / h lidocaine on the spatial memory and non - spatial memory of the aged rats after the operation of the POCD model can be well controlled . The activation of astrocytes in the hippocampus and hippocampus of the aged rats and the expression of GFAP by astrocytes in the hippocampus and hippocampus of the aged rats can be significantly reduced .
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R614

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 楊澤勇;徐瑩華;費鳳英;呂浩;李泉;楊立群;俞衛(wèi)鋒;;老年患者術(shù)后認(rèn)知功能障礙與IL-1β、IL-6和TNF-α的表達(dá)[J];臨床麻醉學(xué)雜志;2010年09期

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