異氟醚致老年大鼠認(rèn)知能力下降與大腦神經(jīng)元NMDAR2B及GABAR1的表達(dá)相關(guān)
發(fā)布時(shí)間：2018-09-07 07:47
【摘要】：術(shù)后認(rèn)知功能障礙(postoperative cognitive dysfunction,POCD)是一種于麻醉及手術(shù)后出現(xiàn)的認(rèn)知功能退化的中樞神經(jīng)系統(tǒng)并發(fā)癥,尤其以老年患者多見(jiàn)。其主要臨床表現(xiàn)為人格的改變、記憶的損傷以及社交減退。POCD可延長(zhǎng)老年患者的住院時(shí)間,增加患者的病死率,嚴(yán)重的影響了患者術(shù)后的生活質(zhì)量。本研究擬通過(guò)探究不同濃度及不同持續(xù)時(shí)間的異氟醚吸入對(duì)老年大鼠認(rèn)知功能障礙以及不同腦區(qū)NMDAR2B和GABAR1表達(dá)的影響。本研究通過(guò)對(duì)100只雄性SD老年大鼠,隨機(jī)分組,分別為對(duì)照組(C組20只)和實(shí)驗(yàn)組(S組80只)。各組大鼠均于處理前進(jìn)行為期五天的水迷宮實(shí)驗(yàn),以使其能夠產(chǎn)生穩(wěn)定記憶。對(duì)照組吸入室溫空氣,實(shí)驗(yàn)組按照藥物濃度和吸入持續(xù)時(shí)間分為S1組(1.5%-2h),S2組(2.5%-2h),S3組(1.5%-4h),S4組(2.5%-4h)。C組和S組均分別在吸入室溫空氣和不同濃度藥物后1、7 d進(jìn)行Morris水迷宮實(shí)驗(yàn)來(lái)測(cè)試其學(xué)習(xí)記憶能力,并在測(cè)試結(jié)束兩小時(shí)后進(jìn)行開(kāi)顱取腦,采用實(shí)時(shí)熒光定量多聚核苷酸鏈?zhǔn)椒磻?yīng)和免疫熒光技術(shù)檢測(cè)海馬及顳葉的GABAR1和NMDAR2B的mRNA的轉(zhuǎn)錄水平和蛋白表達(dá)水平。通過(guò)Morris水迷宮測(cè)試結(jié)果,我們發(fā)現(xiàn)吸入異氟醚1d后的各實(shí)驗(yàn)組大鼠的穿越平臺(tái)次數(shù)與對(duì)照組相比有明顯下降,且隨著藥物濃度的增高和吸入持續(xù)時(shí)間的增加,大鼠學(xué)習(xí)記憶能力下降程度越明顯;各實(shí)驗(yàn)組大鼠的逃避潛伏期與對(duì)照組相比出現(xiàn)延長(zhǎng),且與藥物濃度增高和藥物持續(xù)時(shí)間的增加有一定相關(guān)性。吸入異氟醚7 d后,S1,S2,S3組大鼠的穿越平臺(tái)次數(shù)和逃避潛伏期與對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義,但S4組大鼠穿越次數(shù)明顯低于對(duì)照組和其他三組,逃避潛伏期時(shí)間明顯長(zhǎng)于對(duì)照組和其他三組。并且大鼠這種改變與我們應(yīng)用免疫熒光及實(shí)時(shí)熒光PCR檢測(cè)出來(lái)的結(jié)果是一致的。免疫熒光及實(shí)時(shí)熒光定量PCR顯示,吸入異氟醚1d后的各實(shí)驗(yàn)組大鼠顳葉及海馬中GABAR1的蛋白含量及轉(zhuǎn)錄水平與對(duì)照組相比明顯上調(diào),且隨著藥物濃度的增高和吸入持續(xù)時(shí)間的增加上調(diào)的越明顯。吸入異氟醚7d后的S1,S2,S3組中GABAR1的蛋白含量及轉(zhuǎn)錄水平與對(duì)照組相比差異無(wú)統(tǒng)計(jì)學(xué)意義,而S4組有明顯上調(diào)。另外,免疫熒光及實(shí)時(shí)熒光定量PCR還顯示,吸入異氟醚1d后的各實(shí)驗(yàn)組大鼠顳葉及海馬中NMDAR2B的蛋白含量及轉(zhuǎn)錄水平與對(duì)照組相比明顯下調(diào),且隨著藥物濃度的增高和吸入持續(xù)時(shí)間的增加下調(diào)的越明顯。吸入異氟醚7d后的S1,S2,S3組中NMDAR2B的蛋白含量及轉(zhuǎn)錄水平與對(duì)照組相比差異無(wú)統(tǒng)計(jì)學(xué)意義,而S4組有明顯下調(diào)。進(jìn)而我們也就得出了結(jié)論,持續(xù)吸入異氟醚對(duì)短期空間記憶能力的影響顯著,且長(zhǎng)時(shí)間高濃度的吸入造成的影響時(shí)間較長(zhǎng);異氟醚影響空間記憶能力的改變與NMDAR2B表達(dá)的下調(diào)及GABAR1表達(dá)的上調(diào)相關(guān);吸入異氟醚麻醉不僅造成了海馬區(qū)相關(guān)蛋白的改變,而且在顳葉也發(fā)生了與海馬相似的改變,我們推測(cè)術(shù)后認(rèn)知功能障礙可能是由多腦葉及多腦區(qū)共同參與的。
[Abstract]:Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia and surgery, especially in elderly patients. This study was designed to investigate the effects of isoflurane inhalation with different concentrations and duration on cognitive impairment and the expression of NMDAR2B and GABAR1 in different brain regions in aged rats. The control group inhaled room temperature air. The experimental group was divided into S1 group (1.5% - 2h), S2 group (2.5% - 2h), S3 group (1.5% - 4h), S4 group (2.5% - 4h), C group (2.5% - 4h) and S group (2.5% - 4h). Morris water maze test was performed at 1,7 days after inhalation of air at room temperature and different concentrations of drugs to test their learning and memory abilities. Brain samples were taken two hours after the test. The transcriptional levels of GABAR1 and NMDAR2B mRNA in hippocampus and temporal lobe were detected by real-time fluorescence quantitative polymerase chain reaction and immunofluorescence technique. The results of Morris water maze test showed that the number of crossing platforms in rats inhaled isoflurane decreased significantly compared with the control group one day after inhalation, and with the increase of drug concentration and inhalation duration, the ability of learning and memory of rats decreased more significantly; escape potential of rats in each experimental group After 7 days inhalation of isoflurane, there was no significant difference in the number of crossing platforms and escape latencies between S1, S2 and S3 groups and the control group, but the number of crossing platforms and escape latencies in S4 group were significantly lower than those in the control group and the other three groups. The incubation period was significantly longer than that of the control group and the other three groups, and the changes were consistent with the results detected by immunofluorescence and real-time fluorescence PCR. Immunofluorescence and real-time fluorescence quantitative PCR showed that GABAR1 protein content and transcription level in temporal lobe and hippocampus of rats inhaled isoflurane 1 day after inhalation were compared with the control group. The protein content and transcription level of GABAR1 in S1, S2, S3 groups after inhalation of isoflurane were not significantly different from those in control group, but significantly increased in S4 group. The protein content and transcription level of NMDAR2B in temporal lobe and hippocampus of rats in each experimental group were significantly lower than those in the control group one day after isoflurane inhalation, and the decrease was more obvious with the increase of drug concentration and inhalation duration. The protein content and transcription level of NMDAR2B in S1, S2, S3 groups were lower than those in the control group seven days after isoflurane inhalation. There was no significant difference between the two groups, but the expression of NMDAR2B was down-regulated in group S4. We also concluded that isoflurane inhalation had a significant effect on short-term spatial memory, and the effect of long-term high concentration inhalation was longer; the change of isoflurane on spatial memory was related to the down-regulated expression of NMDAR2B and the up-regulated expression of GABAR1. Inhaled isoflurane anesthesia not only caused changes in hippocampal related proteins, but also similar changes in the temporal lobe and hippocampus. We speculate that postoperative cognitive impairment may be caused by multiple lobes and multiple brain regions.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R614
本文編號(hào)：2227647
[Abstract]:Postoperative cognitive dysfunction (POCD) is a central nervous system complication that occurs after anesthesia and surgery, especially in elderly patients. This study was designed to investigate the effects of isoflurane inhalation with different concentrations and duration on cognitive impairment and the expression of NMDAR2B and GABAR1 in different brain regions in aged rats. The control group inhaled room temperature air. The experimental group was divided into S1 group (1.5% - 2h), S2 group (2.5% - 2h), S3 group (1.5% - 4h), S4 group (2.5% - 4h), C group (2.5% - 4h) and S group (2.5% - 4h). Morris water maze test was performed at 1,7 days after inhalation of air at room temperature and different concentrations of drugs to test their learning and memory abilities. Brain samples were taken two hours after the test. The transcriptional levels of GABAR1 and NMDAR2B mRNA in hippocampus and temporal lobe were detected by real-time fluorescence quantitative polymerase chain reaction and immunofluorescence technique. The results of Morris water maze test showed that the number of crossing platforms in rats inhaled isoflurane decreased significantly compared with the control group one day after inhalation, and with the increase of drug concentration and inhalation duration, the ability of learning and memory of rats decreased more significantly; escape potential of rats in each experimental group After 7 days inhalation of isoflurane, there was no significant difference in the number of crossing platforms and escape latencies between S1, S2 and S3 groups and the control group, but the number of crossing platforms and escape latencies in S4 group were significantly lower than those in the control group and the other three groups. The incubation period was significantly longer than that of the control group and the other three groups, and the changes were consistent with the results detected by immunofluorescence and real-time fluorescence PCR. Immunofluorescence and real-time fluorescence quantitative PCR showed that GABAR1 protein content and transcription level in temporal lobe and hippocampus of rats inhaled isoflurane 1 day after inhalation were compared with the control group. The protein content and transcription level of GABAR1 in S1, S2, S3 groups after inhalation of isoflurane were not significantly different from those in control group, but significantly increased in S4 group. The protein content and transcription level of NMDAR2B in temporal lobe and hippocampus of rats in each experimental group were significantly lower than those in the control group one day after isoflurane inhalation, and the decrease was more obvious with the increase of drug concentration and inhalation duration. The protein content and transcription level of NMDAR2B in S1, S2, S3 groups were lower than those in the control group seven days after isoflurane inhalation. There was no significant difference between the two groups, but the expression of NMDAR2B was down-regulated in group S4. We also concluded that isoflurane inhalation had a significant effect on short-term spatial memory, and the effect of long-term high concentration inhalation was longer; the change of isoflurane on spatial memory was related to the down-regulated expression of NMDAR2B and the up-regulated expression of GABAR1. Inhaled isoflurane anesthesia not only caused changes in hippocampal related proteins, but also similar changes in the temporal lobe and hippocampus. We speculate that postoperative cognitive impairment may be caused by multiple lobes and multiple brain regions.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R614
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