丁苯酞与奥氮平联合治疗脑卒中后抑郁伴睡眠障碍的临床观察

Clinical observation on the combination of butylphthalide and olanzapine in the treatment of post-stroke depression with sleep disorder

目的研究丁苯酞与奥氮平联合治疗脑卒中后抑郁伴睡眠障碍的疗效,及其对患者神经递质、炎症因子等血清指标的影响。方法前瞻性选取2018年5月至2022年10月华北医疗健康集团峰峰总医院收治的脑卒中后抑郁伴睡眠障碍患者120例,按照随机数字表法分为对照组和观察组,各60例。对照组给予丁苯酞治疗,观察组给予丁苯酞联合奥氮平治疗。比较两组疗效,评估两组汉密尔顿抑郁量表(HAMD17)评分、美国国立卫生研究院卒中量表(NIHSS)评分、匹兹堡睡眠质量指数量表(PSQI)评分、Barthel指数等相关评分的差异,比较两组的多导睡眠监测参数(总睡眠时间、睡眠效率、觉醒次数、入睡潜伏期、REM睡眠潜伏期、REM睡眠比例、深度睡眠比例)、神经递质[去甲肾上腺素(NE)、多巴胺、5-羟色胺(5-HT)]及其他血清指标[视黄醇结合蛋白4(RBP4)、胱抑素C(CysC)、高敏-C反应蛋白(hs-CRP)、红细胞沉降率(ESR)、白细胞介素8(IL-8)]的水平,并观察安全性。结果治疗后,观察组总有效率为91.67%,高于对照组(78.33%),差异有统计学意义(P<0.05)。观察组HAMD17评分、PSQI评分、NIHSS评分分别为(9.89±1.74)、(7.48±1.89)、(7.71±1.31)分,均低于对照组[(12.41±2.03)、(11.98±2.05)、(10.22±1.89)分],观察组Barthel指数为(68.33±8.59)分,高于对照组[(56.96±7.58)分],差异均有统计学意义(P<0.05)。观察组的总睡眠时间、睡眠效率、REM睡眠比例、深度睡眠比例分别为(387.63±71.14)min、(73.22±9.17)%、(27.44±6.58)%、(26.52±8.14)%,均明显高于对照组[(329.98±62.57)min、(61.47±8.83)%、(21.14±6.03)%、(21.39±8.36)%],观察组觉醒次数、入睡潜伏期分别为(4.02±1.26)次、(44.74±10.15)min,均明显低于对照组[(6.23±1.72)次、(51.23±13.34)min],差异均有统计学意义(P<0.05);两组治疗2周后的REM睡眠潜伏期比较,差异无统计学意义(P>0.05)。观察组治疗2周后的NE、多巴胺、5-HT、RBP4、CysC、hs-CRP、ESR、IL-8分别为(53.35±8.98)μg/L、(172.02±25.52)μg/L、(167.25±26.55)μg/L、(26.52±2.15)g/L、(0.66±0.09)mg/L、(11.36±2.13)mg/L、(8.15±1.68)mm/h、(164.12±22.87)ng/L,均明显低于对照组[(76.23±12.14)μg/L、(218.96±34.11)μg/L、(225.03±36.59)μg/L、(33.25±2.25)g/L、(0.74±0.10)mg/L、(15.85±2.74)mg/L]、(10.12±2.11)mm/h、(215.25±26.69)ng/L,差异均有统计学意义(P<0.05)。治疗期间,两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论丁苯酞与奥氮平联合治疗脑卒中后抑郁伴睡眠障碍可改善睡眠质量,减少抑郁情绪,可能与调节神经递质,降低RBP4、CysC、hs-CRP、ESR、IL-8表达有关。

Objective To study the efficacy of the combination of butylphthalide and olanzapine in the treatment of post-stroke depression with sleep disorders and its effect on serum indices of neurotransmitters and inflammatory factors in patients.Methods A total of 120 patients with post-stroke depression and sleep disorders admitted to Fengfeng General Hospital,North China Medical Health Group from May 2018 to October 2022 were prospectively selected.The patients were divided into the control group and the observation group according to the random number table method,each group 60 cases.The control group was given butylphthalide treatment,and the observation group was given butylphthalide combined with olanzapine treatment.The efficacy of two groups was compared,and the differences in hamilton depression scale(HAMD17)scores,National Institutes of Health Stroke Scale(NIHSS),pittsburgh sleep quality index scale(PSQI),Barthel index and other scores between the two groups were evaluated.The polysomnography parameters(total sleep time,sleep efficiency,number of awakenings,sleep onset latency,REM sleep latency,REM sleep proportion,deep sleep proportion),neurotransmitters[norepinephrine(NE),dopamine,serotonin(5-HT)]and related factors[retinol binding protein 4(RBP4),cystatin C(CysC),high-sensitivity C-reactive protein(hs-CRP),erythrocyte sedimentation rate(ESR),interleukin-8(IL-8)]of two groups were compared,and safety of two groups were observed.Results After treatment,the total effective rate of the observation group was 91.67%,which was higher than that of the control group(78.33%),and the difference was statistically significant(P<0.05).The HAMD17 score,PSQI score,and NIHSS score of the observation group were(9.89±1.74),(7.48±1.89),(7.71±1.31)points,which were lower than those of the control group[(12.41±2.03),(11.98±2.05),and(10.22±1.89)points],and the Barthel index of the observation group was(68.33±8.59)points,which was higher than those of the control group[(56.96±7.58)points],and the differences were statistically significant(P<0.05).The total sleep time,sleep efficiency,proportion of REM sleep,and proportion of deep sleep in the observation group were(387.63±71.14)min,(73.22±9.17)%,(27.44±6.58)%,and(26.52±8.14)%,respectively,which were significantly higher than those in the control group[(329.98±62.57)min,(61.47±8.83)%(21.14±6.03)%,(21.39±8.36)%],and the number of awakenings and sleep latency in the observation group were(4.02±1.26)times and(44.74±10.15)min,respectively,which were significantly lower than those in the control group[(6.23±1.72)times and(51.23±13.34)min],and the differences were statistically significant(P<0.05).and there was no statistically significant difference in the REM sleep latency after treatment between the two groups(P>0.05).The levels of NE,dopamine,5-HT,RBP4,CysC,hs-CRP,ESR,and IL-8 in the observation group were(53.35±8.98)μg/L,(172.02±25.52)μg/L,(167.25±26.55)μg/L,(26.52±2.15)g/L,(0.66±0.09)mg/L,(11.36±2.13)mg/L,(8.15±1.68)mm/h,and(164.12±22.87)ng/L,respectively,which were significantly lower than that in the control group[(76.23±12.14)μg/L,(218.96±34.11)μg/L,(225.03±36.59)μg/L,(33.25±2.25)g/L,(0.74±0.10)mg/L,(15.85±2.74)mg/L],(10.12±2.11)mm/h,(215.25±26.69)ng/L],and the differences were statistically significant(P<0.05).During the treatment period,there was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Butylphthalein combined with olanzapine in the treatment of post-stroke depression with sleep disorders can improve sleep quality and reduce depressive mood,which may be related to the regulation of neurotransmitters and the reduction of the expression of RBP4,CysC,hs-CRP,ESR and IL-8.