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七氟醚暴露对大鼠认知功能及海马神经元凋亡影响的性别差异

The gender difference in effect of sevoflurane exposure on cognitive function and hippocampus neuronal apoptosis in rats.

作者信息

Xie H, She G-M, Wang C, Zhang L-Y, Liu C-F

机构信息

Department of Anesthesiology, The Second Affiliate Hospital of Soochow University, Suzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2015 Feb;19(4):647-57.

Abstract

OBJECTIVE

Anesthesia and surgery can induce postoperative cognitive dysfunction. Ser-133 phosphorylation sites of cAMP-response element binding protein (CREB) is a key gene that mediate a variety of downstream transcription initiation factors, regulate neuronal survival and promote the expression of a large number of genes. Thus, CREB may play a role in this impairment. We hypothesize that and sevoflurane-induced cognitive impairment possibly via inhibiting the expression of CREB downstream genes and proteins.

MATERIALS AND METHODS

To test this hypothesis, adult Sprague-Dawley rats were subjected to sevoflurane exposure and were tested with a series of behavioral experiments (open field, passive avoidance test and Morris water maze test) at different time (1 d to 95 d). Besides, blood gas changes and expiratory sevoflurane concentrations were examined at 2 h; the levels of phosphorylated CREB 1, the protein Bcl-2, Caspase-8 and Caspase-3 were assessed at 1 week and 3 months after anesthesia. We also conducted a comparison in sevoflurane-induced cognitive impairment between male and female rats.

RESULTS AND CONCLUSIONS

Here, we found that sevoflurane anesthesia can impair short-term cognitive function, which may be via down-regulating p-CREB1 and Bcl-2 expression and up-regulating Caspase-8 expression to reduce hippocampus neuronal apoptosis, and male rats suffered a more severe cognitive dysfunction than female rats. In addition, sevoflurane can produce a reversible long-term cognitive dysfunction in rats.

摘要

目的

麻醉和手术可诱发术后认知功能障碍。环磷酸腺苷反应元件结合蛋白(CREB)的丝氨酸133磷酸化位点是一个关键基因,可介导多种下游转录起始因子,调节神经元存活并促进大量基因的表达。因此,CREB可能在这种损伤中发挥作用。我们推测七氟醚诱导的认知障碍可能是通过抑制CREB下游基因和蛋白质的表达。

材料与方法

为验证这一假设,成年Sprague-Dawley大鼠接受七氟醚暴露,并在不同时间(1天至95天)进行一系列行为实验(旷场试验、被动回避试验和莫里斯水迷宫试验)。此外,在2小时时检测血气变化和呼出的七氟醚浓度;在麻醉后1周和3个月时评估磷酸化CREB 1、蛋白Bcl-2、半胱天冬酶-8和半胱天冬酶-3的水平。我们还比较了雄性和雌性大鼠在七氟醚诱导的认知障碍方面的差异。

结果与结论

在此,我们发现七氟醚麻醉可损害短期认知功能,这可能是通过下调p-CREB1和Bcl-2的表达以及上调半胱天冬酶-8的表达来减少海马神经元凋亡,并且雄性大鼠的认知功能障碍比雌性大鼠更严重。此外,七氟醚可在大鼠中产生可逆的长期认知功能障碍。

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