本文選題：丙泊酚 + 手術(shù)　； 參考：《南昌大學》2017年碩士論文

【摘要】：目的:組蛋白去乙�；窰DAC2通過環(huán)磷酸腺苷效應元件結(jié)合蛋白CREB調(diào)控N-甲基-D-天冬氨酸受體NR2B亞基表達影響學習記憶。課題組前期研究發(fā)現(xiàn),孕期母體丙泊酚麻醉暴露損害子代學習記憶,但HDAC2-CREB-NR2B信號通路在其中的作用不清楚。本研究擬探討孕中期母鼠丙泊酚麻醉手術(shù)對子代學習記憶的影響及HDAC2-CREB-NR2B信號通路在其中的作用。方法:將雌性SD大鼠隨機分為丙泊酚麻醉4h組(P4組)、丙泊酚麻醉手術(shù)4h組(P4S組),對照組(C組)和脂肪乳劑組(I組)。于孕14天(E14),P4組孕鼠接受丙泊酚麻醉4h;P4S組孕鼠接受丙泊酚麻醉4h并復合手術(shù);C組給予等容量(2ml/kg)生理鹽水;I組給予等容量(2ml/kg)脂肪乳劑。各組子鼠出生后亞分為SAHA、Senegenin(SEN)和溶媒DMSO亞組。SAHA亞組子鼠每次Morris水迷宮(MWM)前經(jīng)腹腔注射90mg/kg HDAC2抑制劑SAHA;SEN亞組子鼠經(jīng)腹腔注射15mg/kg遠志皂苷遠SEN;DMSO亞組子鼠經(jīng)腹腔注射等體積溶媒DMSO,每天1次,連續(xù)7天。子鼠出生后30 d(P30)進行MWM實驗測定學習記憶功能。取子鼠海馬組織,免疫組化(IHC)測定子鼠海馬區(qū)HDAC2、p-CREB、NR2B蛋白表達,TUNNEL染色測定子鼠海馬區(qū)神經(jīng)元凋亡。結(jié)果:孕中期母鼠丙泊酚麻醉損害子代學習記憶功能,引起海馬神經(jīng)元凋亡,上調(diào)子代海馬區(qū)HDAC2蛋白表達,下調(diào)p-CREB和NR2B蛋白表達。手術(shù)加劇上述變化。SAHA可減輕上述變化,但對子代海馬神經(jīng)元凋亡無明顯影響。SEN可減輕學習記憶功能損害、減輕NR2B表達變化和抑制子代海馬神經(jīng)元凋亡,對HDAC2和p-CREB蛋白表達無明顯影響。結(jié)論:中期母體接受丙泊酚麻醉通過損害海馬神經(jīng)元、破壞HDAC2-CREB-NR2B信號通路損害子代大鼠學習記憶,手術(shù)可通過該通路加劇子代學習記憶損害。HDAC2抑制劑SAHA可通過上述通路改善子代大鼠學習記憶。遠志皂苷元SEN通過逆轉(zhuǎn)NR2B表達改善子代學習記憶,其確切機制需要深入研究。
[Abstract]:Aim: histone deacetylase HDAC2 regulates the expression of N- methyl-Daspartic acid receptor NR2B subunit through cyclic adenosine effector element binding protein CREB. Our previous study found that maternal propofol anesthetic exposure impaired learning and memory in offspring, but the role of HDAC2-CREB-NR2B signaling pathway was unclear. The purpose of this study was to investigate the effect of propofol anesthesia on learning and memory in offspring and the role of HDAC2-CREB-NR2B signaling pathway. Methods: female Sprague-Dawley rats were randomly divided into propofol anesthesia group (4 h), control group (C group) and fat emulsion group (group I). On the 14th day of gestation, the pregnant rats in the E14 / P4 group received propofol anesthesia for 4 h and the pregnant rats in the P4S group received propofol anesthesia for 4 h and the rats in the combined operation group C were given the same volume of 2 ml / kg / kg of normal saline and 2 ml / kg / kg fat emulsion. After birth, each group was subdivided into two subgroups: SAHAA Senegenin (SEN) and solvent DMSO subgroup. SAHA subgroup. (Morris water maze) before intraperitoneal injection of 90mg/kg HDAC2 inhibitor SAHADAC2 inhibitor SAHASENSEN subgroup (intraperitoneal injection of the same volume of DMSO-DMSO), once a day, the mice of the SAHADAC2 inhibitor SAHADAC2 DMSO subgroup were intraperitoneally injected with the same volume of DMSO-DMSO. Seven days in a row. The learning and memory function was measured by MWM experiment. The expression of HDAC2P-CREBN NR2B protein in hippocampal area was determined by immunohistochemistry and Tunel staining was used to detect neuronal apoptosis in hippocampal area. Results: during the second trimester of pregnancy, propofol anesthesia impaired learning and memory function of offspring, induced apoptosis of hippocampal neurons, up-regulated HDAC2 protein expression and down-regulated the expression of p-CREB and NR2B proteins. These changes were attenuated by operation. SAHA had no obvious effect on the apoptosis of hippocampal neurons in offspring. SEN could alleviate the impairment of learning and memory function, decrease the expression of NR2B and inhibit the apoptosis of hippocampal neurons in offspring. The expression of HDAC2 and p-CREB protein was not affected. Conclusion: propofol anesthesia can damage hippocampal neurons and HDAC2-CREB-NR2B signaling pathway, and impair the learning and memory of offspring by propofol anesthesia. SAHA, an inhibitor of HDAC2, can improve the learning and memory of offspring rats through the above pathway. By reversing the expression of NR2B, SEN improves the learning and memory of offspring, and its exact mechanism needs further study.
【學位授予單位】：南昌大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R614

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本文編號：2028853