神经元兴奋性在右美托咪定保护老龄大鼠术后认知功能中的作用

目的探索神经元兴奋性在右美托咪定保护老龄大鼠术后认知功能中的作用。方法将SD老龄大鼠随机分为假手术组、生理盐水对照组、右美托咪定组。手术前30 min,右美托咪定组大鼠腹腔注射右美托咪定50μg/kg,假手术组和生理盐水对照组大鼠腹腔注射等量生理盐水。在麻醉状态下对右美托咪定和生理盐水组行右侧肾脏切除术,假手术组除不切除肾脏外,其余操作与前两组一致。术前1~4 d及术后1~7 d通过水迷宫检测大鼠的空间学习和记忆功能;术后1~7 d,分别采用免疫组织化学染色进行c-fos和TUNEL标记,酶联免疫吸附(ELISA)法检测海马脑区白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的含量,高效液相色谱检测海马脑区谷氨酸释放量。结果术前1~4d,三组大鼠寻找平台所需时长相比差异无统计学意义(P> 0. 05),且随着训练次数的增加,三组大鼠寻找到平台所用的时间均逐渐降低;术后1~7 d,假手术组相比,生理盐水对照组大鼠寻找平台潜时、脑区c-fos表达阳性面积百分比、神经元凋亡水平、海马脑区IL-1β和TNF-α含量以及谷氨酸释放量均显著增加(P <0. 05),而与生理盐水对照组相比,右美托咪定组以上指标均显著减少或降低(P <0. 05);术后,与假手术组相比,生理盐水对照组大鼠在平台在目标象限停留时间百分比显著降低(P <0. 001);而与生理盐水对照组相比,右美托咪定组大鼠在平台在目标象限停留时间百分比显著增加(P <0. 001);术后,右美托咪定组大鼠相关指标改善程度随药物作用时长而增强。结论术前注射右美托咪定可以通过降低神经元兴奋性对老龄大鼠术后认知功能起到保护作用,且其作用效果随作用时长增加而增加。

The role of neuronal excitability in the protection of postoperative cognitive function in elderly rats with dexmedetomidine

Objective To explore the role of neuronal excitability in the protection of dexmedetomidine on postoperative cognitive function in elderly rats. Methods SD rats were randomly divided into mock surgical group,saline control group and dexmedetomidine group. 30 min before operation,mice in the mock surgical group and saline control group were intraperitoneally injected with the same amount of normal saline,and mice in the dexmedetomidine group were intraperitoneally injected with dexmedetomidine at 50 μg/kg. Saline control group and dexmedetomidine group were performed right nephrectomy under anesthesia,and the operation of the sham operation group was the same as that of the previous two groups except that the kidney was not removed. The learning and memory functions of bow and arrow in rats were tested by water maze at 1 to 4 days before surgery and 1 to 7 days after surgery. At 1 to 7 days after operation,C-fos and TUNEL were labeled by immunohistochemical staining,the contents of IL-1β and TNF-α in the hippocampus were detected by ELISA,and the release of glutamate in hippocampus was detected by HPLC. Results There was no significant difference in the length of time required for the three groups of rats to find the platform 1 to 4 days before the operation( P > 0. 05),and as the number of training sessions increased,the three groups of rats used the platform to find the platform.Time gradually decreases;1 to 7 days after surgery,compared with the sham operation group,the saline control group sought platform latency,the percentage of positive c-fos expression area in the brain area,the level of neuronal apoptosis,and the levels of IL-1β and TNF-α in the hippocampus and the release of glutamic acid increased significantly( P < 0. 05),compared with the normal saline control group,the above indicators were significantly reduced or decreased( P < 0. 05). After surgery,compared with the sham operation group,the percentage of time spent in the target quadrant of the saline control group was significantly reduced( P < 0. 001). Compared with the saline control group,the percentage of dexmedetomidine group rats staying on the platform in the target quadrant significantly increased( P < 0. 001). After operation,the improvement of related indexes in the dexmedetomidine group increased with the duration of drug action. Conclusion Preoperative injection of dexmedetomidine can protect the postoperative cognitive function of aged rats by reducing neuronal excitability,and its effect increases with the duration of action.