髓系分化因子88／核因子-κB信号通路在七氟醚麻醉诱发老龄大鼠认知功能改变中的作用

Myeloid differentiation factor 88/nuclear factor-KB signaling pathway and sevoflurane-induced cognitive deficits in aging rats

目的探讨髓系分化因子88（myeloid differentiation factor 88，MyD88）／NF．KB信号通路在七氟醚麻醉诱发老龄大鼠认知功能改变中的作用。方法雄性SD大鼠，20月龄，体重550—750g，根据随机数字表法分为3组（每组15只）：对照组（C组）、七氟醚处理组（S组）、ST2825＋七氟醚处理组（IS组）。S组和IS组大鼠吸入4％七氟醚6h，C组仅吸入空气-氧气混合气体；IS组大鼠在七氟醚处理前行侧脑室注射MyD88抑制剂ST2825，C组和S组仅侧脑室注射等量生理盐水。采用Morris水迷宫实验及旷场实验评价老龄大鼠认知功能，采用凝胶迁移实验法测定海马组织中NF-κB活性，采用real-timePCR法测定海马组织中TNF-α、IL-1β的表达，采用Western blot法测定淀粉样蛋白（amyloid β，Aβ）42的表达。结果与C组比较，S组在七氟醚麻醉后2～4d逃避潜伏期延长，跨格次数和直立次数减少，中央格停留时间延长，海马组织中NF-κB活性增加，TNF-α和IL-1β mRNA表达增加，Aβ42表达明显增加（P均〈0．05）；与S组比较，IS组七氟醚麻醉后2～4d逃避潜伏期缩短，跨格次数和直立次数增加，中央格停留时间缩短，海马组织中NF-κB活性降低，TNF-α和IL 1wmRNA表达降低，Aw42表达明显降低（P均〈0．05）。结论七氟醚麻醉诱发老龄大鼠认知功能障碍的机制可能与海马中MyD88／NF-κB信号通路激活相关。

Objective To explore the relationship between myeloid differentiation factor 88 （MyD88）/NF-κB signaling pathway and sevoflurane- induced cognitive deficit in aging rats. Methods Twenty months old male SD rats were randomly divided into 3 groups （n=15）： control （C group）, sevoflurane treatment （S group）, and sevoflurane plus ST2825 treatment （IS group）. The rats in S and IS groups were subjected to inhalation of 4% sevoflurane for 6 h, but the rats in C group inhaled air only. The rats in IS group received microinjection of ST2825 via lateral ventricle 10 min before sevoflurane exposure. The cognitive function was assessed with Morris water maze test and open field test. NF-KB activity was assessed with EMSA assay. The expression of TNF-α and IL-1β mRNA in the hippocampus were assessed with real-time PCR assay. The expressions of amyloid β （Aβ）42 were assessed with Western blot assay. Results Compared with C group, there were significant increases of escape latency period, the time the rats spent in the central square, activity of NF-κB, levels of TNF-α mRNA, IL-1β mRNA and Aβ42, but significant decreases of the number of grid crossing and the number of rearing in S group （P〈0.05）. Compared with S group, there were significant decreases of escape latency period, the time spent in the central square, activity of NF-KB, levels of TNF-α mRNA, IL-1β mRNA and Aβ42, but increases of the number of grid crossing and the number of rearing in IS group （P〈0.05）. Conclusions Sevoflurane-indueed cognitive dysfunction in aging rats could be associated with activation of MyD88/NF-κB signaling pathway.