石杉碱甲与POCD模型大鼠海马CA1区ChAT表达相关性的研究

Study on the correlation between huperzine A and choline acetyltransferase in CA1 region of POCD-model rat's hippocampus

目的探讨腹部的手术操作对老年大鼠学习认知能力的影响和海马CA1区胆碱乙酰转移酶(ChAT)阳性神经元的变化以及石杉碱甲干预的结果。方法20月龄Wistar大鼠32只,随机分为对照组(C组)、麻醉组(A组)、手术组(O组)和石杉碱甲组(Hup组),Hup组手术前给予石杉碱甲灌胃3周,3周后O组与Hup组行脾切除术。术后1、3、7 d进行水迷宫测试,术后7 d取脑使用免疫组织化学法观测海马CA1区ChAT的表达。结果术后1 d进行水迷宫测试,与C组比较,A组、O组潜伏期和游泳距离均延长(P<0.05);术后3 d,与C组比较,O组、Hup组潜伏期和游泳距离进一步延长,而Hup组与O组比较,潜伏期和游泳距离均缩短(P<0.05);术后7 d,O组与C组比较,潜伏期和游泳距离延长程度缩小。术后7 d,与C组、Hup组比较,O组的平台象限停滞时间百分比以及在平台象限游泳距离占总游泳距离百分比均减小(P<0.05)。术后7 d,O组海马CA1区ChAT阳性细胞数较C组和Hup组增多(P<0.05)。结论老年大鼠脾切除术后早期可出现认知功能障碍(POCD),海马CA1区ChAT表达上调,预先给予石杉碱甲0.15 mg/kg(连续3周)可以改善POCD模型大鼠学习记忆的功能。

Objective To evaluate the effect of abdominal surgery on the learning and cognitive ability in aged rats and the change of choline acetyltransferase（CHAT） neurons in CA1 region in hippocampus and the result of the intervention of huperzine A. Methods 32 Wistar aged rats were randomly divided into control group （ C, n = 8 ） , anesthesia group （ A, n = 8 ） , operation group （ O, n = 8 ） and huperzine A group （ Hup, n = 8 ）, the Hup group were administered huperzine A for three weeks before operation, after three weeks group O and group Hup received splenectomy. Morris water maze test was performed on the 1 st, 3 rd and 7 th day after operation, the animals were killed in 1 h after the last test and the brains were immediately removed for determination of ChAT expression in CA1 region in hippocampus using immunohistochemistry. Results Morris water maze test was performed on the 1 st day after operation, compared with group C, the latency period and swimming distance of groups A and C both extended （ P 〈 0. 05 ）. On the 3 rd day after operation, compared with group C, the latency period and swimming distance of group O, group Hup extended further, while compared with group O, the latency period and swimming distance of group Hup shortened （ P 〈 0. 05 ） ; Compared with group C, the extending degree of the latency period and swimming distance of group O decreased on the 7 th day after operation. Compared with group C and group Hup, beth of the mean percentage of time and distance of group 0 spent swimming in the quadrant with platform shortened （ P 〈 0. 05 ）. Compared with groups C and Hup, the quantities of ChAT neurons in CA1 region in hippocampus of group O increased on the 7 th day after operation（ P 〈0. 05 ） ,while the quantities of ChAT neurons in CA1 region in hippocampus of group C were equal to that of group Hup. Conclusion Cognitive impairment appeared in the early stage after splenectomy on aged rats, ChAT expression in CA1 region in hippocampus up-regulated, administering huperzine A 0. 15 mg/kg for three consecutive weeks before operation can improve the cognitive ability of rats which suffered postoperative cognitive dysfunction （ POCD ）.