顺铂术前化疗对老龄大鼠术后认知功能及海马NMDA受体表达的影响  

Effects of Neo-adjuvant Chemotherapy with Cisplatin on POCD and NMDAR Expression in Aged Rats

作　　者：程静[1] 刘晓清[1] 操隆辉[1] 钟忠健[1] 张天华[1] 李慧婷[1] 林文前[1] 

机构地区：[1]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心麻醉科,广东广州510060

出　　处：《中山大学学报（医学科学版）》2016年第3期359-366,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81101668);广东省科技计划项目(2014A020212388)

摘　　要：[目的]探讨顺铂术前化疗对老龄大鼠术后认知功能及海马组织NMDA受体表达的影响.[方法]健康雌性SD大鼠30只,10-12月龄,按随机数字表法,将大鼠分为两组（n=15）：生理盐水组（Normal saline injection group）和顺铂组（Cisplatin injection group）.顺铂组经腹腔注射顺铂3 mg/kg,每周1次,共3次.生理盐水组经腹腔注射等容量生理盐水.完成注射后将上述两组分别分为6组（n=5）：单纯生理盐水组（S组）、生理盐水＋麻醉组（SP组）、生理盐水＋麻醉＋手术组（SPO组）、单纯顺铂组（C组）、顺铂＋麻醉组（CP组）、顺铂＋麻醉＋手术组（CPO组）.完成3次注射后的第5天,SP组、SPO组、CP组和CPO组以3％戊巴比妥麻醉至翻正反射消失,其中SPO组和CPO组麻醉后行剖腹探查术.手术后第1天开始,即在第21 ～ 25天采用Morris水迷宫评价认知功能的改变,用免疫印迹法和免疫组化法评价海马组织NMDA受体的表达水平.[结果]顺铂组与生理盐水组相比体质量明显减小,CPO组逃避潜伏期较S、SP、SPO组延长,在原平台所在象限时间较S、SP、SPO组缩短,CPO组NMDAR1、NMDAR2A、NMDAR2B蛋白表达较SPO组减少,免疫组化C、CPO组NMDAR1和NMDAR2A表达较SPO组减少.[结论]顺铂术前化疗可加重老龄大鼠术后认知功能障碍的程度,其机制可能与顺铂引起海马组织NMDA受体表达下调有关.[ Objective] To evaluate the effects of neo-adjuvant chemotherapy with cisplatin on POCD and NMDAR expression in hippocampus in aged rats. [Methods] Thirty female Sprague-Dawley rats, aged 10-12 months, were randomly divided into 2 groups using a random number table： normal saline injection group and cisplatin injection group. Rats in cisplatin injection group were injected cisplatin intraperitoneally once a week at a dose of 3mg/kg for 3 weeks. Rats in normal saline injection group were injected with an equivalent volume of saline （i.p.） in lieu of cisplatin. After the injections, the 2 groups were divided into 6 groups （n = 5 each）： normal saline group （group S）, normal saline ＋ pentobarbital group （group SP）, normal saline ＋ pentobarbital ＋ operation group （group SPO）, cisplatin group （group C）, cisplatin ＋ pentobarbital group （group CP）, cisplatin ＋ pentobarbital ＋ operation group （group CPO）. Morris water maze test was performed to evaluate the spatial learning and memory ability. After the test, their hippocampi were removed for detection of the expression of NMDAR by western blot and immunohistochemistry. [Results] Compared with normal saline injection group, cisplatin injection group had a lower weight. Compared with group S and SP and SPO, the mean escape latency was longer in group CPO, while the time in target quadrant is shorter. Compared with group SPO, the NMDAR1, NMDAR2A, NMDAR2B protein expressions were decreased in group CPO. Compared with group SPO, the NMDARl and NMDAR2A immunohistochemistry staining were decreased in group C and group CPO. [Conclusion] Neo-adjuvant chemotherapy with cisplatin could exacerbate the postoperative cognitive dysfunction and decreased the NMDAR level in hippocampus in aged rats.

关 键 词：顺铂 新辅助化疗 术后认知功能障碍 NMDA 

分 类 号：R619.9[医药卫生—外科学]