刘天琳 瞿敏

[摘要]目的 探討尼莫地平对烧伤大鼠认知功能的影响及其作用机制。方法 选择健康的18月龄SD雄性大鼠32只。用随机数字表法将大鼠分为4组（n=8）：对照组（C组）、手术组（S组）、尼莫地平组（D组）、尼莫地平+手术组（D+S组）。D、D+S组腹腔注射1 mg/kg尼莫地平，C、S组给予等量生理盐水;30 min后S组和D+S组给予麻醉后造烧伤模型;C组为空白对照组。术前1 d及术后第1、3、7天采用Morris水迷宫实验记录大鼠逃避潜伏期和穿越次数。Morris水迷宫完成后处死大鼠取海马，采用ELISA检测海马区的肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）;采用RT-PCR法测定海马Bax、Bcl-2的mRNA表达量。流式细胞仪测量海马神经元凋亡率。结果 C、D组术后第1、3、7天平均逃避潜伏期、穿越次数与术前1 d比较，差异无统计学意义（P>0.05）。与C组比较，S、D+S组术后第1、3、7天的平均逃避潜伏期延长、穿越次数减少（P<0.05）。与S组比较，D+S组术后第1、3、7天的平均逃避潜伏期缩短、穿越次数增加（P<0.05）。与S组比较，D+S组大鼠海马区TNF-α、IL-6水平降低，Bax mRNA表达量降低，Bcl-2 mRNA表达量升高，Bax/Bcl-2比值降低，凋亡率降低，差异有统计学意义（P<0.05）。结论 尼莫地平可通过抑制炎症反应、降低海马神经元凋亡改善烧伤老龄大鼠术后认知功能障碍。

[关键词]尼莫地平;凋亡率;认知功能;烧伤

[中图分类号] R614.1          [文献标识码] A          [文章编号] 1674-4721（2020）7（c）-0012-05

Effect of Nimodipine pretreatment on cognitive function in burned rats

LIU Tian-lin1   QU Min2▲

1. The Second Department of Anesthesiology， Cangzhou Central Hospital， Hebei Province， Cangzhou   061100， China; 2. Department of Anesthesiology， Children′s Hospital of Cangzhou Central Hospital， Hebei Province， Cangzhou   061100， China

[Abstract] Objective To investigate the effect of Nimodipine on cognitive function in burned rats and its mechanism. Methods A total of 32 healthy male SD rats aged 18 months were selected. The rats were divided into four groups （n=24） by random number table method： control group （group C）， surgery group （group S）， Nimodipine group （group D）， Nimodipine + surgery group （group D+S）. Groups D and D+S were intraperitoneally injected with 1mg/kg Nimodipine， while groups C and S were given the same amount of normal saline; 30 min later， the group S and group D+S were anesthetized and burned models were created. Group C was the blank control group. Morris water maze method was used to record the escape latency and crossing times of rats 1 day before operation and the 1st， 3rd， 7th days after operation. After completing， the Morris water maze， the rats were sacrificed and their hippocampus were collected. The tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the hippocampus were detected by ELISA. MRNA expressions of hippocampal Bax and Bcl-2 were determined by RT-PCR. The apoptosis rate of hippocampal neurons was measured by flow cytometry. Results Compared with 1 day before the operation， there were no significant differences in the average escape latent period and crossing times between group C and group D on the 1st， 3rd， and 7th days after operation （P>0.05）. Compared with group C，the average escape latent period of group S and D+S was prolonged and the crossing times were reduced on the 1st，3rd and 7th days after operation （P>0.05）. Compared with group S ， the average escape latent period of the group D+S at the same time was shortened and the crossing times at the same time were increased on the 1st，3rd and 7th days （P<0.05）. Compared with group S， the levels of TNF-α and IL-6 in the hippocampus of the rats in the group D+S were decreased， the mRNA expression of Bax in hippocampal neurons was reduced， the mRNA expression of Bcl-2 was increased， the ratio of Bax/Bcl-2 was reduced， and the apoptosis rate was decreased （P<0.05）. Conclusion Nimodipine can improve postoperative cognitive dysfunction in burned elderly rats by inhibiting inflammatory response and decreasing hippocampal neuron apoptosis.

[Key words] Nimodipine; Apoptosis rate; Cognitive function; Burned

认知功能障碍是术后常见的神经精神并发症，多见于老年人，可导致住院时间延长，影响术后生活质量，甚至影响患者转归，危及生命。术后认知功能障碍的机制非常复杂，有炎症、氧化应激、凋亡、自噬等[1]，目前凋亡机制是当前研究热点之一[2]。

烧伤一般是指由热力、蒸汽、高温气体、火焰等引起的皮肤和/或黏膜的组织损伤[3]。重度烧伤常伴有多个器官、系统的损伤。随着烧伤的治疗理念日趋完善、治疗方法不断精进，烧伤病死率明显降低，而其引起的精神障碍逐渐成为主要问题之一。Palmu等[4]研究认为，在平均烧伤面积为9%总体表面积的烧伤患者中精神疾患发病率为60%。烧伤不……