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Objective: To observe the clinical efficacy of Xinglou Chengqi Decoction in the treatment of cognitive impairment after ischemic stroke with phlegm-heat and bowel-repletion type based on the theory of “brain-gut interaction”.
A total of 144 patients of cognitive impairment after ischemic stroke with phlegm-heat and bowel-repletion type were included, and randomly divided into the treatment group and control group, 72 cases in each group. All the patients were treated with basic treatment of ischemic stroke and donepezil hydrochloride tablets orally. Based on above, the patients in the control group were orally treated with lactulose oral solution and the patients in the treatment group were orally treated with Xinglou Chengqi Decoction, with a course of 30 d. Before treatment and after 30 and 90 d of treatment, the scores of mini-mental state examination (MMSE) in the two groups were evaluated. After 90 d of treatment, the effect of cognitive function improvement was compared between the two groups. Before treatment and after 30 and 90 d of treatment, the expression levels of serum 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP) and motilin (MTL) were detected.
During the course of research, 5 patients in the control group and 7 patients in the treatment group were eliminated and shed off, finally 67 patients in the control group and 65 patients in the treatment group were included in the statistical analysis. ①After 90 d of treatment, the scores of MMSE in the two groups were increased compared with those before treatment (P<0.05), and the score of the treatment group was higher than that of the control group (P<0.05). ②After 90 d of treatment, the total effective rates on cognitive function improvement of the treatment group and the control group were 89.23% and 74.63% respectively, and the effect of the treatment group was better than that of the control group (P<0.05). ③After 30 d of treatment, the levels of 5-HT, CGRP and MTL in the two groups were increased compared with those before treatment (P<0.05), and the levels of above indexes in the treatment group were higher than those in the control group (P<0.05). After 90 d of treatment, the levels of 5-HT, CGRP and MTL in the treatment group were increased compared with those before treatment (P<0.05), the levels of 5-HT and MTL in the control group were also increased compared with those before treatment (P<0.05), and the levels of 5-HT, CGRP and MTL in the treatment group were higher than those in the control group (P<0.05).
Based on the conventional western medicine, Xinglou Chengqi Decoction can effectively improve the cognitive function in patients of cognitive impairment after ischemic stroke with phlegm-heat and bowel-repletion type, and regulate the expression levels of serum brain-gut peptide indexes, thus play the effect of “brain-gut interaction”.
认知障碍是缺血性中风常见的后遗症,严重影响患者的康复疗效,降低生活质量,缩短生存时间,且增加了家庭和社会的负担。因此,早期识别和治疗中风后患者存在的认知障碍具有重要的现实意义。“脑肠互动”理论是近十余年来用以解释大脑与胃肠道系统之间密切关系的学说,有研究证实,脑肠肽在沟通大脑与胃肠道之间扮演着双向调控的角色[
1.1.1 西医诊断标准
参照《中国急性缺血性脑卒中诊治指南2018》[
1.1.2 中医辨证标准
参照《中风病诊断与疗效评定标准》[
1.2.1 纳入标准
符合上述缺血性中风及中风后认知障碍的诊断标准,且简易智能状态检查量表(mini-mental state examination, MMSE)评分≤24分;符合上述中风病痰热腑实型辨证标准;中风发生后72 h内入院;年龄>30岁;意识清楚,能单独完成神经心理学评估;自愿受试,并签署知情同意书。
1.2.2 排除标准
由于脑肿瘤、脑外伤、血液病等引起的卒中患者;合并有心血管、肝、肾、造血系统、免疫系统等严重原发性疾病者;既往认知功能下降或痴呆、精神异常、严重酗酒者;既往存在消化道出血、功能障碍及肿瘤患者。
1.2.3 剔除、脱落标准
不符合纳入标准而被误入者;抵触中医药治疗,或依从性差、不遵医嘱服药、自行加用化痰通便中西药物者;不按时随访者;发生病情变化、严重不良事件或并发症等影响研究者;自行中途退出者。
本研究纳入病例来源于2020年9月至2021年11月在温州市中西医结合医院就诊的296例缺血性中风后认知障碍患者,其中痰热腑实型患者172例,最终纳入本研究者144例。采用随机数字表将纳入患者随机分配至治疗组和对照组,每组各72例。本试验已在中国临床试验注册中心注册(编号:ChiCTR2000040910),并获得温州市中西医结合医院伦理委员会审批通过[批号:伦研批快(2020-13)号],所有受试者或其直系亲属均签署知情同意书。
缺血性中风的基础治疗参考相关指南[
1.5.1 MMSE评分及认知功能改善疗效评价
于治疗前及治疗30、90 d后,采用MMSE评估患者的认知功能状态,MMSE总分为30分,分值越高提示认知能力越好,MMSE评分≤24分者可诊断为认知障碍[
1.5.2 脑肠肽水平
于治疗前及治疗30、90 d后,采集所有患者的清晨空腹外周静脉血,采用酶联免疫吸附法检测患者的血清5-羟色胺(5-hydroxytryptamine, 5-HT)、降钙素基因相关肽(calcitonin gene related peptide, CGRP)、胃动素(motilin, MTL)表达水平。
1.5.3 安全性评价
于治疗前及治疗30、90 d后,检测所有患者的血常规、肝功能、肾功能、电解质等指标水平及心电图,并详细记录与治疗相关的不良反应发生情况,评价治疗的安全性。
研究采用SPSS 26.0软件对数据进行统计分析。计量资料以ˉx±s表示,符合正态分布者组间比较采用独立样本t检验,组内治疗前后比较采用配对样本t检验;不符合正态分布者采用Mann-Whitney U检验。计数资料以例数或百分比表示,非等级计数资料采用χ2检验,等级计数资料采用秩和检验。以P<0.05为差异有统计学意义。
研究过程中,对照组因病情变化、拒绝采血或失访而剔除或脱落者5例,中药组因无法坚持服药、病情变化、拒绝采血或失访而剔除或脱落者7例,最终纳入统计分析者对照组67例、治疗组65例。两组患者的性别构成、年龄、体质量指数(body mass index, BMI)、发病到入院时间、美国国立卫生研究院卒中量表(National Institute of Health stroke scale, NIHSS)评分、糖化血红蛋白水平、血压及牛津郡社区卒中计划(Oxfordshire community stroke project, OCSP)分型比较,差异均无统计学意义(P>0.05),具有可比性。见
观察项目 | 治疗组(n=65) | 对照组(n=67) |
---|---|---|
性别[例(%)] | ||
女性 | 19(29.23) | 26(38.81) |
男性 | 46(70.77) | 41(61.19) |
年龄(ˉx±s,岁) | 65.62±12.35 | 66.52±9.86 |
BMI(ˉx±s,kg/m2) | 23.23±3.21 | 23.35±2.68 |
发病到入院时间(ˉx±s,h) | 17.54±10.79 | 16.94±16.20 |
NIHSS评分(ˉx±s,分) | 9.23±4.42 | 9.81±5.08 |
糖化血红蛋白(ˉx±s,%) | 6.41±1.23 | 6.57±1.81 |
血压(ˉx±s,mmHg) | ||
收缩压 | 151.28±23.24 | 154.04±22.26 |
舒张压 | 84.06±17.09 | 84.73±14.72 |
OCSP分型[例(%)] | ||
TACI | 10(15.38) | 11(16.42) |
PACI | 34(52.31) | 38(56.72) |
POCI | 16(24.62) | 15(22.39) |
LACI | 5(7.69) | 3(4.48) |
注: TACI为全前循环脑梗死(total anterior circulation infarct),PACI为部分前循环脑梗死(partial anterior circulation infarct),POCI为后循环脑梗死(posterior circulation infarct),LACI为腔隙性脑梗死(lacunar infarct)
治疗前,两组患者的MMSE评分比较,差异无统计学意义(P>0.05)。治疗30 d后,两组患者的MMSE评分与治疗前比较及组间比较,差异均无统计学意义(P>0.05);治疗90 d后,两组患者的MMSE评分较治疗前均升高(P<0.05),且治疗组患者的评分高于对照组(P<0.05)。见
组 别 | n | 治疗前 | 治疗30 d后 | 治疗90 d后 |
---|---|---|---|---|
治疗组 | 65 | 18.91±3.03 | 20.05±2.90 | 25.11±4.27*# |
对照组 | 67 | 19.15±3.85 | 19.88±4.01 | 22.72±4.20* |
注: 与本组治疗前比较,*P<0.05;与对照组同期比较,#P<0.05
治疗90 d后,治疗组患者的认知功能改善疗效总有效率为89.23%,对照组为74.63%,治疗组的疗效优于对照组(P<0.05)。见
组 别 | n | 显著改善 | 改善 | 无效 | 加重 | 总有效率(%) |
---|---|---|---|---|---|---|
治疗组 | 65 | 52 | 6 | 5 | 2 | 89.23 |
对照组 | 67 | 35 | 15 | 12 | 5 | 74.63 |
治疗前,两组患者的5-HT、CGRP、MTL水平比较,差异均无统计学意义(P>0.05)。治疗30 d后,两组患者的5-HT、CGRP、MTL水平较治疗前均升高(P<0.05),且治疗组患者的上述指标水平高于对照组(P<0.05);治疗90 d后,治疗组患者的5-HT、CGRP、MTL水平较治疗前均升高(P<0.05),对照组患者的5-HT、MTL水平较治疗前亦升高(P<0.05),且治疗组患者的5-HT、CGRP、MTL水平均高于对照组(P<0.05)。见
组 别 | n | 时点 | 5-HT(μg/L) | CGRP(ng/L) | MTL(ng/L) |
---|---|---|---|---|---|
治疗组 | 65 | 治疗前 | 120.72±20.35 | 77.83±8.33 | 233.40±19.43 |
治疗30 d后 | 147.63±25.02*# | 92.54±17.49*# | 323.74±38.51*# | ||
治疗90 d后 | 145.22±24.73*# | 90.18±18.19*# | 311.34±40.73*# | ||
对照组 | 67 | 治疗前 | 122.24±32.61 | 77.69±9.09 | 234.42±21.48 |
治疗30 d后 | 132.40±26.06* | 84.99±14.35* | 295.81±41.15* | ||
治疗90 d后 | 135.16±32.17* | 81.46±14.33 | 292.06±41.35* |
注: 与本组治疗前比较,*P<0.05;与对照组同期比较,#P<0.05
研究过程中,所有患者的血常规、肝功能、肾功能指标及心电图等均未发生与治疗相关的异常变化,但对照组中7例患者出现不良反应、不良反应发生率为10.45%,治疗组中11例患者出现不良反应、不良反应发生率为16.92%,两组不良反应发生率比较,差异无统计学意义(P>0.05)。见
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令人困惑的是,星蒌承气汤是如何达到以下治上、釜底抽薪的治疗效果呢?近十余年来,有学者提出“脑肠互动”理论,用以解释大脑与胃肠道系统之间密切关联[
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