PSD-95/Kalirin-7/Rac1信号通路对不同浓度七氟烷吸入麻醉大鼠胃癌根治术后神经功能的影响

Effect of PSD-95/Kalirin-7/Rac1 signaling pathway on nerve function after radical gastarectomy under sevoflurane inhalation anesthesia in rats

目的探讨突触后致密蛋白95(postsynaptic density protein-95, PSD-95)/Kalirin-7/Ras相关的C3肉毒杆菌毒素底物1(ras-related C3 botulinum toxin substrate 1, Rac1)信号通路对不同浓度七氟烷吸入麻醉大鼠胃癌根治术后神经功能的影响。方法 Wistar大鼠52只,随机选取9只为正常组,其余43只制备胃癌模型并将存活的40只随机分为模型组和七氟烷低、中、高浓度组各10只。七氟烷低、中、高浓度组分别吸入体积分数1%、3%、5%七氟烷麻醉后行胃癌根治术,正常组和模型组不行手术。比较5组术后谵妄情况、Bederson神经功能评分、海马组织病理变化情况、海马组织PSD-95、Kalirin-7蛋白相对表达量和磷酸化Rac1(phosphorylated-Rac1, p-Rac1)/Rac1。结果大鼠周边运动格数和中央跨格次数随七氟烷浓度增高而增加(P<0.05),中央停留时间随七氟烷浓度增加而延长(P<0.05),且不同浓度七氟烷组均大于模型组和正常组(P<0.05)。术后1、3、5 d,七氟烷高浓度组Bederson神经功能评分[(2.15±0.31)、(2.85±0.31)、(3.24±0.32)分]均高于七氟烷中浓度组[(1.64±0.17)、(2.26±0.23)、(2.70±0.28)分]和七氟烷低浓度组[(1.02±0.13)、(1.57±0.16)、(2.03±0.21)分](P<0.05),七氟烷中浓度组高于七氟烷低浓度组(P<0.05);随术后时间延长,七氟烷低、中、高浓度组Bederson神经功能评分均逐渐升高,不同时间点比较差异均有统计学意义(P<0.05)。HE染色结果显示,正常组与模型组神经元排列整齐,大部分神经元形态、结构正常;七氟烷低、中、高浓度组海马神经元排列紊乱,部分神经元胞体变小,有较多神经元发生不同程度固缩与深染,随七氟烷浓度增高改变更为明显。PSD-95蛋白、Kalirin-7蛋白相对表达量,p-Rac1/Rac1随七氟烷浓度增加而降低(P<0.05),均低于模型组和对照组(P<0.05)。结论七氟烷可导致大鼠胃癌根治术后谵妄及神经功能障碍,且呈剂量依赖性,其作用机制可能与抑制PSD-95/Kalirin-7/Rac1信号通路有关。

Objective To investigate the effect of postsynaptic density protein-95(PSD-95)/Kalirin-7/Ras related ras-related C3 botulinum toxin substrate 1(Rac1) signaling pathway on nerve function after radical gastarectomy under sevoflurane inhalation anesthesia in rats. Methods In 52 Wistar rats, 9 rats were randomly selected as normal group. The rest 43 rats were established gastric cancer models, in which 40 survived rats were randomly divided into model group, low-concentration sevoflurane group, medium-concentration sevoflurane group and high-concentration sevoflurane group, with 10 rats in each group. Low-, medium-and high-concentration sevoflurane groups inhaled 1%, 3% and 5% sevoflurane for anesthesia before radical resection of gastric cancer, while normal group and model group received no treatment. The delirium, neural function score, hippocampal histopathological changes, the relative expressions of PSD-95 and Kalinin-7 protein, and phosphorylated-Rac1(p-Rac1)/Rac1 were compared among five groups. Results The number of peripheral motion grids and central span grids increased with the increase of sevoflurane concentration(P<0.05), and the central dwelling time prolonged with the increase of sevoflurane concentration, which were significantly higher than those in normal group and model group. The Bederson neurological scores on the 1 st, 3 rd and 5 th postoperative days were higher in high-concentration sevoflurane group(2.15±0.31, 2.85±0.31, 3.24±0.32) than those in medium-concentration sevoflurane group(1.64±0.17, 2.26±0.23, 2.70±0.28) and low-concentration sevoflurane group(1.02±0.13, 1.57±0.16, 2.03±0.21)(P<0.05), and higher in medium-concentration sevoflurane group than the those in low-contentration sevoflurane group(P<0.05);they increased gradually with time prolongation after operation in three groups(P<0.05), and showed significant differences among different time points(P<0.05). The HE staining results showed that the neurons were arranged neatly, most of the neurons had normal morphology and structure in normal group and model group;the hippocampal neurons were disorderly arranged, some neurons had smaller cell bodies,and more neurons contracted and stained in varying degrees,which was more significant with the increase of sevoflurane concentration in low-,medium-,and high-concentration sevoflurane groups.The relative expressions of PSD-95 and Kalinin-7 proteins as well as p-Rac1/Rac1 decreased gradually with the increase of sevoflurane concentration(P<0.05),and were lower than those in model group and control group(P<0.05).Conclusion Sevoflurane may cause delirium and neurological dysfunction after radical gastarectomy in rats,in a dose-dependent tendency,probably by inhibiting PSD-95/Kalirin-7/Rac1 signaling pathway.