手术加剧孕中期丙泊酚暴露导致的子代大鼠学习记忆损害

发布时间：2018-06-17 00:57

本文选题：丙泊酚 + 手术　；参考：《南昌大学》2017年硕士论文

【摘要】：目的:组蛋白去乙酰化酶HDAC2通过环磷酸腺苷效应元件结合蛋白CREB调控N-甲基-D-天冬氨酸受体NR2B亚基表达影响学习记忆。课题组前期研究发现,孕期母体丙泊酚麻醉暴露损害子代学习记忆,但HDAC2-CREB-NR2B信号通路在其中的作用不清楚。本研究拟探讨孕中期母鼠丙泊酚麻醉手术对子代学习记忆的影响及HDAC2-CREB-NR2B信号通路在其中的作用。方法:将雌性SD大鼠随机分为丙泊酚麻醉4h组(P4组)、丙泊酚麻醉手术4h组(P4S组),对照组(C组)和脂肪乳剂组(I组)。于孕14天(E14),P4组孕鼠接受丙泊酚麻醉4h;P4S组孕鼠接受丙泊酚麻醉4h并复合手术;C组给予等容量(2ml/kg)生理盐水;I组给予等容量(2ml/kg)脂肪乳剂。各组子鼠出生后亚分为SAHA、Senegenin(SEN)和溶媒DMSO亚组。SAHA亚组子鼠每次Morris水迷宫(MWM)前经腹腔注射90mg/kg HDAC2抑制剂SAHA;SEN亚组子鼠经腹腔注射15mg/kg远志皂苷远SEN;DMSO亚组子鼠经腹腔注射等体积溶媒DMSO,每天1次,连续7天。子鼠出生后30 d(P30)进行MWM实验测定学习记忆功能。取子鼠海马组织,免疫组化(IHC)测定子鼠海马区HDAC2、p-CREB、NR2B蛋白表达,TUNNEL染色测定子鼠海马区神经元凋亡。结果:孕中期母鼠丙泊酚麻醉损害子代学习记忆功能,引起海马神经元凋亡,上调子代海马区HDAC2蛋白表达,下调p-CREB和NR2B蛋白表达。手术加剧上述变化。SAHA可减轻上述变化,但对子代海马神经元凋亡无明显影响。SEN可减轻学习记忆功能损害、减轻NR2B表达变化和抑制子代海马神经元凋亡,对HDAC2和p-CREB蛋白表达无明显影响。结论:中期母体接受丙泊酚麻醉通过损害海马神经元、破坏HDAC2-CREB-NR2B信号通路损害子代大鼠学习记忆,手术可通过该通路加剧子代学习记忆损害。HDAC2抑制剂SAHA可通过上述通路改善子代大鼠学习记忆。远志皂苷元SEN通过逆转NR2B表达改善子代学习记忆,其确切机制需要深入研究。
[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.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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