调神健脾针法治疗腹泻型肠易激综合征的临床疗效评价及脑fMRI改变的研究

发布时间：2018-07-09 12:48

本文选题：调神健脾针法 + 腹泻型肠易激综合征　；参考：《南京中医药大学》2017年博士论文

【摘要】：目的:评价调神健脾针法治疗腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome,IBS-D)的包括肠道症状、精神症状(焦虑、抑郁、睡眠障碍)的整体疗效;同时基于静息态功能磁共振(resting state functional magnetic resonance imaging,Rs-fMRI),探讨调神健脾针法治疗IBS-D的中枢机制。方法:1、调神健脾针法治疗IBS-D的临床疗效评价将符合临床研究招募标准的118例IBS-D患者,采用中央随机系统按2:1比例随机分为针刺组(调神健脾针法组)79例和西药组(匹维溴铵片组)39例。分别给予6周的相应治疗,针刺组予调神健脾针法,穴取百会、印堂、太冲、天枢、上巨虚、足三里、三阴交,隔日针刺1次,每周3次,连续6周;西药组予匹维溴铵片口服,每次50mg,每日3次,连续6周。治疗前及治疗1、2、4、6周对两组患者的临床观察指标包括症状严重程度积分(IBS-symptom severity score,IBS-SSS)、ZUNG 氏焦虑自测量表(self-rating anxiety scale,SAS)、ZUNG 氏抑郁自测量表(self-rating depression scale,SDS)进行评估;治疗前、治疗6周结束时对匹兹堡睡眠质量评分(pittsburgh sleep quality index,PSQI)进行评估;6周治疗结束后进行疗效评价和安全性评价。2、基于Rs-fMRI的调神健脾针法治疗IBS-D疗效的中枢机制研究一共纳入符合磁共振研究招募标准的IBS-D患者组18例和健康对照组21例,予患者组调神健脾针法治疗6周(具体操作方法同临床疗效评价部分),健康对照组不干预。患者组于治疗前后进行临床观察指标(IBS-SSS、SAS、SDS、PSQI)评估和静息态功能磁共振数据采集。健康对照组入组前进行临床观察指标(SAS、SDS、PSQI)的评估,入组后进行静息态功能磁共振数据采集。运用低频振幅(amplitude oflowfrequency fluctuation,ALFF)法和局部一致性(regional homogeneity,ReHo)法对两组的静息态功能磁共振数据分析,比较治疗前患者组与健康对照组的脑功能差异,以及患者组治疗前后的脑功能变化,并将治疗前后差异脑区的ALFF、ReHo的变化值和临床观察指标的改善值进行相关分析,以确定调神健脾针法作用的靶向脑区。结果:1、调神健脾针法治疗IBS-D的临床疗效评价结果(1)共有9例IBS-D患者脱落,针刺组脱落3例,西药组脱落6例。故最后共有109例IBS-D患者纳入统计分析,针刺组76例,西药组33例。(2)两组的一般情况及各项基线评分资料比较没有统计学差异(P0.05),具有可比性。(3)主要疗效评价显示:针刺组的痊愈率、愈显率均较西药组高(P0.05,0.01),总有效率也高于西药组(P0.05),表明针刺组总体疗效更好。(4)次要疗效评价显示:①IBS症状严重程度积分(IBS-SSS)评价结果IBS-SSS总积分比较:经重复测量方差分析显示,6周治疗后,两组IBS-D患者的IBS-SSS总积分都下降(P=0.0000.01);两组间整体比较,IBS-SSS总积分没有表现出有统计学意义的差异(P=0.0800.05),但是P值较小,有出现统计学差异的趋势,结合数值看有针刺组的IBS-SSS总积分较西药组更低的趋势。两组间各观测时点比较,只有第6周时,IBS-SSS总积分的组间比较有统计学差异(P=0.0010.0125),其余时间点(第1、2、4周时),均未出现统计学差异(P=0.339,0.015,0.0310.0125),但第2、4周的P值较小(P=0.015,0.031),说明有出现统计学差异的趋势,结合数值看针刺组的IBS-SSS总积分较西药组更低,且这种差异性有出现在治疗的较早期(第2周)的可能性。综上,针刺组IBS-SSS总积分的改善略优于西药组。IBS-SSS各单项分值比较:在治疗后的各观测时点(第1、2、4、6周),针刺组的腹痛程度、腹痛天数、腹胀程度、排便满意度、生活影响五项分值均较治疗前降低(P0.0125);在治疗后的各观测时点(第1、2、4、6周),西药组的腹痛程度、腹痛天数、排便满意度三项分值均较治疗前降低(P0.0125),而腹胀程度、生活影响两项分值只在治疗后第4周和第6周显示出降低(P0.0125),前两周的观测时点未出现统计学差异(P0.0125)。组间比较,治疗2周时,针刺组的生活影响分值较西药组低(P=0.0120.0125),其余各项分值比较均无统计学意义差异(P0.0125);治疗6周时,针刺组的腹痛程度、腹痛天数、生活影响三项分值较西药组低(P=0.002,0.003,0.0030.0125),腹胀程度、排便满意度两项分值比较均无统计学意义差异(P0.0125);治疗1周和4周时,两组间各单项分值比较,均没有统计学意义的差异(P0.0125)。②ZUNG氏焦虑自测量表(SAS)的评价结果经重复测量方差分析显示,6周治疗后,两组IBS-D患者的SAS自评分都下降(P=0.0000.01);两组间整体比较,SAS自评分没有表现出统计学意义的差异(P=0.0980.05),但是P值较小,有出现统计学差异的趋势,结合数值看有针刺组的SAS自评分较西药组有更低的趋势。各观测时点两组间比较均未出现有统计学意义的差异(P0.0125),但是治疗第6周的P值为0.028,值较小,亦有出现针刺组的SAS分值低于西药组的趋势。另外,从两组的各自SAS评分下降趋势和具体数值来看,西药组在最后2周时SAS分值略有波动,针刺组的作用更为平稳。③ZUNG氏抑郁自测量表(SDS)的评价结果经重复测量方差分析显示,6周治疗后,两组IBS-D患者的SDS自评分都下降(P=0.0000.01);但两组SDS分值改善的整体差异不显著(P0.05),且在各观测时点进行两组间SDS分值比较,未发现SDS分值有统计学意义的差异(P0.0125)。然而,从两组的各自SDS评分下降趋势和具体数值来看,西药组在最后2周时SDS分值略有波动,针刺组的作用更为平稳。④匹兹堡睡眠质量评分(PSQI)的评价结果经6周治疗后,两组与各自治疗前比较,针刺组患者的PSQI评分下降明显(P0.01),西药组患者的PSQI评分变化不明显(P0.05)。组间比较,两组治疗前后PSQI评分差值的比较,差异有统计学意义(P0.05),从数值上看,针刺组患者的PSQI评分下降较西药组患者更明显。(5)安全性评价只有1例脱落的西药组患者服药后症状加重,可能存在药物不良反应。其余所有纳入患者均无针刺或药物不良反应,亦无肝肾功能异常变化。2、基于Rs-fMRI的调神健脾针法治疗IBS-D中枢机制研究结果(1)18例IBS-D患者组中脱落1例,故只有17例患者进入统计分析,健康对照组21例全部进入统计分析。(2)两组的一般情况比较没有统计学差异(P0.05),具有可比性;但IIBS-D患者组的焦虑、抑郁、睡眠的基线评分均较健康对照组高(P0.01)。(3)调神健脾针法治疗后,IBS-D患者组各项临床观察指标均下降,具体为:症状严重度总积分(IBS-SSS)(P0.01)、腹痛程度(P0.01)、腹胀程度(P0.05)、排便满意度(P0.01)、焦虑自评分(SAS)(P0.01)、抑郁自评分(SDS)(P0.01)、匹兹堡睡眠质量评分(PSQI)均下降(P0.01),有效率为88.2%,与临床疗效评价部分结果基本一致,适合进行静息态功能磁共振研究。(4)调神健脾针法治疗前,患者组与健康对照组的脑功能差异:与健康对照组比较,患者组ALFF值降低的脑区有左侧颞上回、颞中回,左侧角回;ReHo值降低的脑区有双侧补充运动区、额内回、右额上回;未发现ALFF值和ReHo值升高脑区。两个指标降低的脑区均主要位于新皮层。(5)调神健脾针法治疗后,患者组的脑功能变化:与治疗前比较,患者组ALFF值升高的有双侧颞叶的颞上回、颞中回、颞横回,左侧脑岛,右侧海马,双侧枕叶的距状裂周围皮层、舌回;ALFF值降低的有左前扣带,左壳核;ReHo值升高的有双侧颞叶的颞上回、颞横回,左侧颞中回,左侧脑岛,双侧枕叶的距状裂周围皮层,额内回,双侧补充运动区;ReHo值降低的有双侧前扣带,左壳核。两个指标升高的脑区主要位于新皮层,降低的脑区主要位于边缘系统。(6)调神健脾针法作用的靶向脑区:治疗前后,左前扣带的ALFF值的变化和腹胀程度分值的改善有正相关关系(r =0.501,P=0.0400.05),未发现其他差异脑区变化和临床观察指标改善有相关性。结论:1、调神健脾针法治疗IBS-D,在改善IBS-SSS症状总积分以及缓解腹痛程度、减少腹痛频率、改善生活影响、提高睡眠质量方面疗效优于西药匹维溴铵片,尤其是改善生活影响方面,在治疗的较早期(第2周)即表现出优势;在缓解腹胀、提高排便满意度、改善焦虑和抑郁情绪方面疗效与西药匹维溴铵片相当,但改善焦虑和抑郁方面的作用较西药匹维溴铵片平稳;总体疗效优于西药匹维溴铵片。2、基于Rs-fMRI,腹泻型肠易激综合征患者和健康受试者的脑功能存在差异,部分新皮层脑区的低频振幅和局部一致性降低,可能是IBS-D的重要中枢病理变化。调神健脾针法治疗后,IBS-D患者的脑功能变化主要为部分新皮层脑区的低频振幅和局部一致性升高,部分边缘系统脑区的低频振幅和局部一致性降低,其中左前扣带的变化与腹胀改善相关。因此,调神健脾针法治疗IBS-D具有肠道和精神症状兼治的作用,整体疗效更好;其临床疗效的中枢机制之一可能在于对边缘系统-新皮层相关脑区的良性调节,使其恢复平衡,涉及协调内脏痛觉网络、情绪调控网络、认知调控网络内部及网络间关系,其中左前扣带可能是其改善内脏感觉的靶向脑区;中枢机制之二可能是对默认模式网络的良性调节。
[Abstract]:Objective: To evaluate the overall efficacy of diarrhea-predominant irritable bowel syndrome (IBS-D) in the treatment of diarrhea type irritable bowel syndrome (bowel syndrome, IBS-D), and to explore the effects of mental symptoms (anxiety, depression, sleep disorders), and based on the resting state functional magnetic resonance (resting state functional magnetic resonance imaging, Rs-fMRI). The central mechanism of regulating the spleen and invigorating the spleen method for the treatment of IBS-D. Methods: 1, the evaluation of the clinical efficacy of IBS-D with the method of regulating the spleen and invigorating the spleen will be in line with the recruitment criteria of 118 cases of IBS-D patients. The central random system is randomly divided into 79 cases and 39 cases in the western medicine group (Pinaverium Bromide Tablets group). According to the corresponding treatment, the acupuncture group was given the method of regulating the spleen and invigorating the spleen, taking Baihui, printing hall, Tai Chou, Tianshu, Zusanli, three yin, 1 times a week, 3 times a week for 6 weeks. The western medicine group gave Pinaverium Bromide Tablets oral, each time 50mg, 3 times a day for 6 weeks. The clinical observation indexes of two groups before and after treatment and treatment were serious symptoms including severe symptoms. IBS-symptom severity score (IBS-SSS), ZUNG's anxiety self-test scale (self-rating anxiety scale, SAS), the ZUNG's depression self-measurement scale (self-rating depression) was evaluated; the Pittsburgh sleep quality score was evaluated at the end of the treatment and 6 weeks of treatment. After the end, the efficacy evaluation and safety evaluation were.2, and the central mechanism of the treatment of IBS-D based on Rs-fMRI's regulating the spleen and invigorating spleen method was included in 18 cases of IBS-D patients and 21 cases of the healthy control group, which were conformed to the recruitment criteria of magnetic resonance. The clinical observation index (IBS-SSS, SAS, SDS, PSQI) and resting state functional magnetic resonance data were collected before and after the treatment. The clinical observation index (SAS, SDS, PSQI) was evaluated before the healthy control group, and the resting state functional magnetic resonance data were collected after the group entered, and the low frequency amplitude (amplitude oflow) was used. The frequency fluctuation, ALFF) method and local conformance (regional homogeneity, ReHo) method were used to analyze the resting state functional magnetic resonance data of two groups, compared the brain function difference between the patients before treatment and the healthy control group, as well as the changes of brain function before and after the treatment in the patient group, and the changes of ALFF, ReHo in the different brain regions before and after treatment and the clinical value. The improvement value of the observation index was analyzed in order to determine the target brain area of the method of regulating the spleen and invigorating the spleen. Results: 1, the clinical efficacy evaluation results of the treatment of IBS-D by adjusting the spleen and invigorating spleen method (1) there were 9 cases of IBS-D patients falling off, 3 cases in the acupuncture group and 6 cases in the western medicine group. Finally, there were 109 cases of IBS-D patients included in the statistical analysis, 76 cases in needling group and West. There were 33 cases in the medicine group. (2) the general situation of the two groups and the baseline score data were not statistically different (P0.05). (3) the main curative effect evaluation showed that the healing rate of the acupuncture group was higher than the western medicine group (P0.05,0.01), and the total effective rate was higher than that of the western medicine group (P0.05), indicating that the overall effect of the acupuncture group was better. (4) secondary curative effect evaluation. The results were as follows: (1) the total score of the IBS-SSS score of IBS symptom severity score (IBS-SSS) was compared: after 6 weeks of treatment, the total IBS-SSS score of the two groups of IBS-D patients decreased (P=0.0000.01); the total integral of the two groups had no statistical difference (P=0.0800.05), but the P value was small, There was a trend of statistical difference, and the total score of IBS-SSS in the acupuncture group was lower than that of the western medicine group. Compared with the two groups, there was a statistically significant difference between the two groups at the time of sixth weeks (P=0.0010.0125), and the other time points (1,2,4 weeks) were not statistically different (P=0.339,0.015,0.03 10.0125), but the P value of week 2,4 was smaller (P=0.015,0.031), indicating the trend of statistical difference, combined with the value of the acupuncture group, the total integral of IBS-SSS was lower than that of the western medicine group, and this difference had the possibility of the earlier treatment (second weeks). In conclusion, the improvement of the total integral of IBS-SSS in the acupuncture group was slightly better than that of the.IBS-SSS in the western medicine group. Comparison: in each observation point after treatment (week 1,2,4,6), the abdominal pain degree, abdominal pain days, abdominal distention, defecation satisfaction, and life influence five scores were lower than before treatment (P0.0125). In the observation time points after treatment (week 1,2,4,6), the abdominal pain degree, abdominal pain days, and three points of satisfaction of defecation were all compared. Before treatment (P0.0125), the two scores of abdominal distention and life influence were decreased only at fourth and sixth weeks after treatment (P0.0125), and no statistical difference was found in the first two weeks (P0.0125). After 2 weeks of treatment, the life influence of acupuncture group was lower than that of the Western Medicine group (P=0.0120.0125), and the other scores were no more than that of the western medicine group. Statistical significance difference (P0.0125); at 6 weeks, the three scores of abdominal pain, abdominal pain and life influence in the acupuncture group were lower than that of the western medicine group (P=0.002,0.003,0.0030.0125), the degree of abdominal distention, and the two scores of the satisfaction of defecation were not statistically significant (P0.0125). At the time of 1 and 4 weeks of treatment, there was no comparison between the two groups. The difference of study meaning (P0.0125). (2) the evaluation results of ZUNG's anxiety self-test scale (SAS) showed that after 6 weeks of treatment, the SAS self score of two groups of IBS-D patients decreased (P=0.0000.01), and the overall comparison between the two groups showed that SAS self scoring did not show the difference (P=0.0980.05), but the P value was smaller. There was a lower trend in the SAS score of the acupuncture group compared with the western medicine group. There was no statistically significant difference between the two groups of the observation time points (P0.0125), but the value of P in the sixth week treatment was 0.028, and the value of the SAS in the acupuncture group was lower than that in the western medicine group. In addition, from the two groups. The SAS score of the western medicine group was slightly fluctuated at the last 2 weeks and the effect of the acupuncture group was more stable. (3) the evaluation results of the ZUNG depression self measurement scale (SDS) showed that after 6 weeks of treatment, the SDS self score of two groups of IBS-D patients decreased (P=0.0000.01), but the score of SDS in the two groups was improved. The overall difference was not significant (P0.05), and the SDS score of two groups was compared at every point of observation. The difference of SDS score was not found statistically significant (P0.0125). However, in the last 2 weeks, the value of SDS in the western medicine group fluctuated slightly and the role of the acupuncture group was more stable in the last 2 weeks of the two groups. After 6 weeks of treatment, the results of the evaluation of sleep quality score (PSQI) were compared with the two groups before the treatment. The PSQI score of the patients in the acupuncture group decreased significantly (P0.01), and the PSQI score of the western medicine group was not significant (P0.05). The difference between the two groups before and after the treatment was statistically significant (P0.05). The PSQI score of the patients in the group was more obvious than those in the western medicine group. (5) only 1 cases of the western medicine group had more symptoms and had adverse drug reactions. The rest of the patients had no acupuncture or adverse drug reactions, and there was no abnormal.2 in the liver and kidney function, and the treatment of IBS-D based on Rs-fMRI's regulating the spleen and invigorating the spleen. The results of the central mechanism study (1) 18 cases of IBS-D patients were dropped out of 1 cases, so only 17 patients entered the statistical analysis, and 21 cases in the healthy control group were all entered into statistical analysis. (2) the general situation of the two groups was not statistically different (P0.05), but the baseline score of anxiety, depression and sleep in the IIBS-D group was higher than that of the healthy control group. (P0.01) (3) after the therapy of regulating the spleen and strengthening the spleen, the clinical observation indexes of IBS-D patients were all decreased, specifically: the total score of symptom score (IBS-SSS) (P0.01), abdominal pain (P0.01), abdominal distention (P0.05), defecation satisfaction (P0.01), self rating anxiety (SAS) (P0.01), depression (SDS) (P0.01), and Pittsburgh sleep quality score (PSQI) decreased (P0.01) the effective rate was 88.2%, which was basically consistent with the results of the clinical efficacy evaluation. (4) the difference of brain function between the patient group and the healthy control group before the therapy of adjusting the spleen and invigorating spleen: compared with the healthy control group, the brain area of the patient group with lower ALFF value had the left temporal gyrus, the middle temporal gyrus, the left angular gyrus, and the ReHo value. There were bilateral supplementary motor areas, frontal gyrus, right frontal gyrus, and no ALFF and ReHo value increased in the brain area. The brain areas of the two indexes were mainly located in the neocortex. (5) the brain function of the patient group was changed after the therapy of regulating the spleen and invigorating the spleen: compared with the pre treatment, the ALFF value of the patients was increased with bilateral temporal lobe temporal gyrus, middle temporal gyrus, and temporomandibular. Transverse gyrus, left insula, right hippocampal, bilateral occipital lobe peri cortex, lingual gyrus, left anterior cingulate and left putamen with lower ALFF value, bilateral temporal gyrus, left temporal gyrus, left temporal gyrus, left lateral insula, bilateral occipital lobe peri cortex, frontal gyrus, bilateral supplemental motor area, and bilateral ReHo value decreased in ReHo value. The two indexes of the brain were mainly located in the neocortex and the lower brain area was mainly located in the marginal system. (6) the target brain area of the function of regulating the spleen and invigorating the spleen: the changes of the ALFF value of the left anterior cingulate and the improvement of the degree of abdominal distention were positively correlated (R =0.501, P=0.0400.05) before and after treatment, and there was no other difference in the brain region. Conclusion: 1, the treatment of IBS-D is better than the western medicine Pinaverium Bromide Tablets in improving the total integral of IBS-SSS symptoms, reducing the degree of abdominal pain, reducing the frequency of abdominal pain, improving the life influence and improving the quality of sleep, especially in the improvement of the life effect, in the early period of treatment (second weeks) that is, It showed advantages in alleviating abdominal distention, improving satisfaction of defecation, improving anxiety and depression, compared with western medicine Pinaverium Bromide Tablets, but the effect of improving anxiety and depression was more stable than that of Western medicine Pinaverium Bromide Tablets; the overall effect was better than the western medicine Pinaverium Bromide Tablets.2, Rs-fMRI based, diarrhea type irritable bowel syndrome and healthy subjects The low frequency amplitude and local consistency of the part of the neocortex were reduced, which may be the important central pathological changes of IBS-D. After the therapy of regulating the spleen and invigorating the spleen, the changes in the brain function of the IBS-D patients were mainly the low frequency amplitude and local consistency of the part of the neocortex and the low frequency amplitude of the part of the marginal system brain region. The change of the left anterior cingulate is related to the improvement of abdominal distention. Therefore, the therapy of regulating the spleen and invigorating the spleen for the treatment of IBS-D has the effect of both intestinal and mental symptoms, and the overall effect is better. One of the central mechanisms of its clinical effect may be the benign regulation of the marginal system - the neocortex related brain area, which involves the recovery of balance, involving the recovery of the balance. Coordination of visceral pain network, emotional regulation network, cognitive regulation network internal and inter network relations, the left anterior cingulate may be its target brain area to improve the visceral sense; the two of the central mechanism may be a benign regulation of the default mode network.
【学位授予单位】：南京中医药大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R246.1

【参考文献】