【摘要】 目的：探讨夜预汤对卒中后失眠模型大鼠的治疗作用及其对NF-κB/NLRP3信号通路的影响。方法：将100只Sprague Dawley大鼠随机分为5组，每组20只。通过暂时性大脑中动脉闭塞手术制备大鼠脑卒中模型，脑卒中造模成功后大鼠腹腔注射氯苯丙氨酸（PCPA）混悬液制备失眠模型。卒中后失眠模型建立成功后，艾司唑仑组（500 mg/kg），夜预汤低（500 mg/kg）、高剂量组（1 000 mg/kg）给予相应药物灌胃，持续4周，正常对照组、模型对照组给予等体积的生理盐水。给药结束后，应用水迷宫测试评估大鼠神经功能，同时测定大鼠睡眠时相、神经细胞凋亡水平；应用RT-PCR法及蛋白印迹法测定大鼠脑组织核因子-κB(NF-κB)、结节样受体蛋白3(NLRP3)mRNA与蛋白水平。结果：与模型对照组比较，艾司唑仑组和夜预汤低、高剂量组大鼠逃避潜伏期、觉醒时间（Wake）、凋亡率、NF-κB mRNA、NLRP3 mRNA、NF-κB蛋白、NLRP3蛋白表达明显降低，经过原平台位置次数、原平台象限留时间、慢波睡眠Ⅰ期（SWS1）、慢波睡眠Ⅱ期（SWS2）、快动眼睡眠（REMS）、总睡眠时间（TST）明显升高，且随夜预汤给药剂量增加，逃避潜伏期、Wake、凋亡率、NF-κB mRNA、NLRP3 mRNA、NF-κB蛋白、NLRP3蛋白表达逐渐降低，经过原平台位置次数、原平台象限留时间、SWS1、SWS2、REMS、TST逐渐升高，呈剂量依赖性（P<0.05）；与艾司唑仑组比较，夜预汤低剂量组大鼠逃避潜伏期、Wake、凋亡率、NF-κB mRNA、NLRP3 mRNA、NF-κB蛋白、NLRP3蛋白表达明显升高，经过原平台位置次数、原平台象限留时间、SWS1、SWS2、REMS、TST明显降低（P<0.05）；夜预汤高剂量组与艾司唑仑组大鼠各指标比较，差异均无统计学意义（P>0.05）。结论：夜预汤对卒中后失眠模型大鼠具有明显治疗作用，其机制可能与夜预汤能明显抑制NF-κB、NLRP3基因与蛋白表达进而抑制NF-κB/NLRP3通路激活有关。更多还原

【Abstract】 Objective: To explore the therapeutic effect of Yeyu Decoction on post-stroke insomnia model rats and its influence on NF-κB/NLRP3 signaling pathway. Methods: 100 Sprague Dawley rats were randomly divided into 5 groups, 20 rats in each group. The rat model of stroke was prepared by temporary middle cerebral artery occlusion. After the successful stroke model, the rats were intraperitoneally injected with chlorophenylalanine(PCPA) suspension to prepare the insomnia model. After establishment of the insomnia model after stroke, the esazolam group(500 mg/kg), the low-dose Yeyu Decoction(500 mg/kg) and the high-dose Yeyu Decoction(1 000 mg/kg) were given corresponding drugs by gavage for 4 weeks, and the normal control group and the model control group were given the same volume of normal saline. After the experiment, the water maze test was used to evaluate the neurological function of the rats, and the sleep phase and the apoptosis level of the neurons were determined at the same time. RT-PCR and Western blotting were used to determine the mRNA and protein level of NF-κB and NLRP3 in the rat brain tissue. Results: Compared with the model control group, the escape latency, Wake, apoptosis rate, the mRNA and protein expression of NF-κB and NLRP3 in the estazolam group and the Yeyu Decoction low-dose and high-dose groups were significantly decreased, and the nu mber of times through the original platform position, the time spent in the original platform quadrant,SWS1, SWS2, REMS, and TST were significantly increased, and with the increase of the dose of Yeyu Decoction. The escape latency, Wake, apoptosis rate, the mRNA and protein expression of NF-κB and NLRP3gradually decreased, and the number of times through the original platform position, the time spent in the original platform quadrant, SWS1, SWS2, REMS, and TST gradually increased in a dose-dependent manner(P<0.05). Compared with the estazolam group, the escape latency, Wake, apoptosis rate, the mRNA and protein expression of NF-κB and NLRP3 in the Yeyu Decoction low-dose group were significantly increased, and the number of times through the original platform position, the time spent in the original platform quadrant, SWS1,SWS2, REMS, and TST were significantly decreased(P<0.05). There was no significant difference in each index between the high-dose Yeyu Decoction group and the estazolam group(P>0.05). Conclusion: Yeyu Decoction has obvious therapeutic effect on post-stroke insomnia model rats, and the mechanism may be related to that Yeyu Decoction can significantly inhibit the expression of NF-κB and NLRP3 gene and protein expression, thereby inhibiting the activation of NF-κB/NLRP3 pathway.更多还原