七氟醚复合丙泊酚麻醉对轻度认知功能障碍大鼠术后脑组织hnRNPA2表达的影响
Effect of sevoflurane combined with propofol anesthesia on postoperative expression of hnRNPA2 in brain tissues of rats with mild cognitive impairment
摘要目的 评价七氟醚复合丙泊酚麻醉对轻度认知功能障碍(MCI)大鼠术后脑组织核不均一性核糖核蛋白A2 (hnRNPA2)表达的影响.方法 雄性SD大鼠,16~18月龄,采用结扎双侧颈总动脉致其重度狭窄的方法建立MCI模型.取MCI模型制备成功的大鼠48只,采用随机数字表法分为4组(n=12):假手术组(SH组)、七氟醚麻醉组(S组)、丙泊酚麻醉组(P组)和七氟醚复合丙泊酚麻醉组(SP组).S组吸入3%七氟醚;P组静脉输注丙泊酚40 mg· kg-1·h-1;Sp组吸入1.7%七氟醚,静脉输注丙泊酚20 mg·kg-1,h-1.3组麻醉时间均为3h.待大鼠翻正反射消失后,行胫骨骨折切开复位内固定术.术后7d时行Y迷宫实验,计算新异臂(N臂)停留时间百分比;行旷场实验,记录活动总路程和中央区活动时间;然后处死大鼠,取脑组织,分别采用免疫荧光法和Western blot法测定海马hnRNAP2和γ-氨基丁酸A型受体α1亚基(GABAA-α1)的表达水平.结果 与SH组比较,S组和P组N臂停留时间百分比降低,海马hnRNPA2表达上调,GABAA-α1表达下调,SP组海马hnRNPA2表达上调(P<0.05),N臂停留时间百分比和海马GABAA-α1表达差异无统计学意义(P>0.05);与S组或P组比较,SP组N臂停留时间百分比升高,海马hnRNPA2表达下调,GABAA-α1表达上调(P<0.05);4组间活动总路程及中央区活动时间比较差异无统计学意义(P>0.05).结论 七氟醚复合丙泊酚麻醉不加重MCI大鼠术后认知功能障碍的机制可能与上调脑组织hnRNPA2表达,维持GABAA-α1稳定表达有关.
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abstractsObjective To evaluate the effect of sevoflurane combined with propofol anesthesia on the postoperative expression of nuclear heterogeneous ribonucleoprotein A2 (hnRNPA2) in brain tissues of rats with mild cognitive impairment (MCI).Methods Male Sprague-Dawley rats,aged 16-18 months,were anesthetized with pentobarbital sodium.MCI was induced by ligation of bilateral common carotid arteries after anesthesia.Forty-eight rats with MCI were divided into 4 groups (n =12 each) using a random number table method:sham operation group (SH group),sevoflurane anesthesia group (S group),propofol anesthesia group (P group),and sevoflurane combined with propofol anesthesia group (SP group).Group S inhaled 3% sevoflurane.Propofol was intravenously infused at a rate of 40 mg · kg-1 · h-1 in group P.In group SP,1.7% sevoflurane was inhaled,and propofol 20 mg· kg-1 · h-1 was intravenously infused.The anesthesia time was 3 h in the three groups.After disappearance of eyelash reflex,open reduction and internal fixation was performed after tibial fracture was induced.Y-maze test was performed at 7 days after operation,and the percentage of time of staying at novel arm was calculated.The open field test was performed,and the total activity distance and time of staying at the central region were recorded.Then the rats were sacrificed,and brain tissues were obtained for determination of the expression of hnRNAP2 and γ-aminobutyric acid receptor A1 subunit (GABAA-α1) in hippocampus by immunofluorescence and Western blot,respectively.Results Compared with SH group,the percentage of time of staying at novel arm was significantly decreased,the expression of hnRNPA2 in the hippocampus was up-regulated,and the expression of GABAA-α1 was down-regulated in S and P groups,and the expression of hnRNPA2 in the hippocampus was up-regulated (P<0.05),and no significant change was found in the percentage of time of staying at novel ann or expression of GABAA-α1 in SP group (P> 0.05).Compared with S group or P group,the percentage of time of staying at novel arm was significantly increased,the expression of hnRN-PA2 in the hippocampus was down-regulated,and the expression of GABAA-α1 was up-regulated in SP group (P<0.05).There was no significant difference in the total distance or time of staying at the central region among the four groups (P> 0.05).Conclusion The mechanism by which sevoflurane combined with propofol anesthesia does not aggravate the postoperative cognitive dysfunction may be related to up-regulating the expression of hnRNPA2 in brain tissues and maintaining GABAA-α1 stable in rats with MCI.
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