宁神温胆汤联合利培酮在精神分裂症患者中的临床效果及对免疫功能

doi:10.3969/j.issn.1000⁃484X.2019.14.010
宁神温胆汤联合利培酮在精神分裂症患者中的临床效果及对免疫功能的影响研究
黄兹高　黄　胜　叶　亮　陈圣丽　冯琳丽　(海南省安宁医院中西医内科,海口570100)
中图分类号　R749.3 文献标志码　A 文章编号　1000⁃484X (2019)14⁃1708⁃04
作者简介:黄兹高,男,主治医师,主要从事中西医结合治疗临床常
见疾病相关疑难症状的研究㊂
[摘　要]　目的:探究宁神温胆汤联合利培酮在精神分裂症患者中的临床效果及对免疫功能的影响㊂方法:回顾性分析2016年3月至2018年6月在我院就诊的168例精神分裂症患者的诊疗情况㊂根据治疗方案不同,分为研究组(86例)和对照组(82例),对照组给予利培酮治疗,研究组给予宁神温胆汤联合利培酮治疗㊂治疗3个月后,使用阳性和阴性症状量表(PANSS)和副反应量表(TESS)对患者临床疗效进行评定,并对两组免疫功能相关指标进行比较分析㊂结果:治疗后,研究组PANSS 评分总分㊁阳性症状和阴性症状评分明显低于对照组(P <0.05),研究组TESS 评分明显低于对照组(P <0.05)㊂研究组的临床治疗有效率明显高于对照组(87.21%vs.74.39%,P <0.05)㊂治疗后,研究组IgA㊁IgG㊁IgM 水平均明显低于对照组(P <0.05);且研究组肿瘤坏死因子α(TNF⁃α)㊁白细胞介素6(IL⁃6)㊁IL⁃1β水平也明显低于对照组,两组比较差异有统计学意义(P <0.05)㊂结论:宁神温胆汤联合利培酮疗效确切,可明显改善患者精神状况,降低IgA㊁IgG㊁IgM 及TNF⁃α㊁IL⁃6㊁IL⁃1β水平,
值得临床推广㊂
[关键词]　精神分裂症;宁神温胆汤;利培酮;临床疗效;免疫功能
Clinical effect of ningshen wendan decoction combined with risperidone on patients with schizophrenia and its influence on immune function
HUANG Zi⁃Gao ,HUANG Sheng ,YE Liang ,CHEN Sheng⁃Li ,FENG Lin⁃Li .Medical Department of Traditional Chinese and Western Medicine ,Hainan Anning Hospital ,Haikou 570100,China
[Abstract ]　Objective :To explore the clinical effect of ningshen wendan decoction combined with risperidone on patients with
schizophrenia and its influence on immune function.Methods :The clinical data of 168cases of patients with schizophrenia who received treatment in our hospital from March 2016to June 2018were retrospectively analyzed.Patients were divided into study group (86cases)and control group (82cases)according to different treatment methods.Patients in the control group were treated with risperidone,while patients in the study group were treated with ningshen wendan decoction on the basis of risperidone.After 3months of treatment,patients were evaluated with positive and negative symptom scale (PANSS)and treatment emergent symptoms scale (TESS),and the related indicators of immune function in the two groups were compared and analyzed.Results :After treatment,the PANSS score,positive and negative symptom score of the study group were significantly lower than those of the control group (P <0.05),and TESS score of the study group was significantly lower than that of the control group (P <0.05).The clinical effective rates of the study group was obviously higher than that of the control group,and the difference was statistically significant (87.21%vs.74.39%,P <0.05).After treatment,the levels of IgA,IgG and IgM in the study group were significantly lower than those in the control group (P <0.05).The levels of tumor necrosis factor⁃alpha (TNF⁃α),the interlukin⁃6(IL⁃6)and IL⁃1βin the study group were also significantly lower than those in the control group,and the differences were statistically significant (P <0.05).Conclusion :Ningshen wendan decoction combined with risperidone can be
effective for treatment of patients with schizophrenia,which can significantly improve the mental state of patients and reduce the levels of IgA,IgG,IgM,TNF⁃α,IL⁃6and IL⁃1β.It is worthy of clinical promotion.
[Key words ]　Schizophrenia;Ningshen wendan decoction;Risperidone;Clinical efficacy;Immune function
精神分裂症是一种常见的慢性重症精神疾病,多在青壮年发病,临床常表现为人格改变㊁精神活动与环境不协调等,具有高复发率㊁高致残率的特点,
不仅会对患者的身体和心理造成严重危害,还会给其家庭及社会带来了沉重的负担[1]㊂抗精神病药是目前治疗精神分裂症主要手段之一,非典型抗精神病药如利培酮㊁氯氮平㊁阿立哌唑㊁奥氮平等被临床广泛应用,其对精神分裂症的阳性症状和阴性症状均有较好的治疗效果,且椎体外系反应和迟发性
运动障碍的发生率较低,但长期使用还是会引起血脂异常等代谢紊乱综合征[2,3]㊂研究发现,中西医联合治疗精神疾病,可在一定程度上提高临床效果,降低不良反应发生率㊂宁神温胆汤在临床中可用于治疗胆胃不合㊁虚烦不眠㊁呕吐呃逆等症状,近年来,随着研究深入,人们发现宁神温胆汤在治疗精神疾病方面也具有较好的疗效[4]㊂因此,本研究将宁神温胆汤联合利培酮应用于精神分裂症患者临床治疗中,并对其临床效果及对免疫功能的影响进行了探讨,现报告如下㊂
1　资料与方法
1.1　资料　回顾性分析2016年3月至2018年6月在我院就诊的精神分裂症患者168例,根据治疗方案不同,分为研究组(给予宁神温胆汤联合利培酮治疗)和对照组(给予利培酮治疗)㊂纳入标准:①符合‘中国精神障碍分类与诊断标准第3版“[5]中精神分裂症诊断标准;②阳性和阴性症状量表(Positive and negative symptoms scale,PANSS)总分≥60分;③年龄18~65岁,病程≤3年;④1个月内未服用抗精神病药物㊂排除标准:①合并严重心㊁肝㊁肾等重要脏器疾病;②难治性精神分裂症患者;
③合并感染性疾病㊁免疫性疾病及严重躯体残疾者;
④妊娠期㊁哺乳期女性或计划妊娠者㊂研究组86例,男47例,女39例;年龄20~64岁,平均(34.62±5.41)岁;受教育年限5~16年,平均(12.18±2.64)年;病程3~23个月,平均(11.25±2.73)个月㊂对照组82例,男44例,女38例;年龄19~62岁,平均(34.23±5.16)岁;受教育年限4~16年,平均(11.87±2.90)年;病程4~24个月,平均(11.07±2.65)个月㊂两组患者性别㊁年龄㊁受教育年限㊁病程等一般资料比较,差异无统计学意义(P>0.05)㊂1.2　方法
1.2.1　给药方式　对照组给予利培酮治疗㊂患者口服利培酮片(生产厂家:西安杨森制药有限公司,国药准字:H20010309)治疗,起始量为1mg/d,在1周内根据病情需要调整为2~3mg/d,以后根据患者实际情况逐渐增加药量,剂量范围为4~6mg/d㊂研究组在对照组基础上再给予宁神温胆汤治疗㊂宁神温胆汤组方为酸枣仁10g㊁石菖蒲10g㊁伏苓30g㊁半夏10g㊁竹茹10g㊁枳实10g㊁陈皮10g㊁甘草6g㊁生姜6g㊁大枣6g㊂每日1剂,中药汤剂约
250ml,分早晚2次温服㊂两组患者均以3个月为1个疗程,治疗1个疗程后统计疗效㊂
1.2.2　观察指标　比较两组患者治疗前后临床疗效㊁副反应发生情况及免疫功能情况㊂①临床疗效,采用PANSS[6]进行评定㊂PANSS减分率=(基线分-测定点分)/(基线分-30)×100%,减分率≥75%为痊愈,75%>减分率≥50%为显著进步, 50%>减分率≥25%为好转,25%>减分率为无效,治疗有效率=(痊愈例数+显著进步例数)/总例数×100%;②副反应发生情况,采用副反应量表(Treatment emergent symptoms scale,TESS)[7]进行评定,评价内容包括行为毒性㊁化验㊁神经系统㊁心血管系统及其他,评分项为S严重程度(0~4分)㊁R药物关系(0~4分)㊁T处理(0~6分);③免疫功能评价指标包括:免疫球蛋白IgA㊁IgG㊁IgM和免疫细胞因子TNF⁃α㊁IL⁃6㊁IL⁃1β水平,均采用ELISA法(北京邦定生物技术有限公司)测定㊂
1.3　数据分析　采用SPSS20.0进行统计学分析,计量资料采用t检验比较,计数资料采用χ2检验比较,P<0.05表示差异有统计学意义㊂
2　结果
2.1　两组患者治疗前后PANSS评分比较　治疗前,两组患者PANSS总分㊁阳性症状㊁阴性症状及一般精神病理评分比较,差异无统计学意义(P> 0.05);治疗后,研究组PANSS总分㊁阳性症状和阴性症状评分均明显低于对照组(P<0.05),见表1㊂2.2　两组患者临床治疗有效率比较　研究组和对照组临床治疗有效率分别为87.21%和74.39%,两组比较差异有统计学意义(P<0.05),见表2㊂
表1　两组患者治疗前后PANSS评分比较(x±s,分)
Tab.1　Comparison of PANSS score between two groups before and after treatment(x±s,score)
Groups n Measuring time Positive symptoms Negative symptoms General psychopathology Total score Research group86Before treatment21.82±6.5824.60±6.4945.28±8.1191.70±9.13
After treatment12.18±3.251)10.81±3.641)25.34±6.181)48.33±8.361) Control group82Before treatment22.06±7.0423.92±6.0846.30±7.9692.28±9.54
After treatment13.95±3.371)2)12.83±3.571)2)26.27±6.041)53.05±8.701)2) Note:Compared with the same group before treatment,1)P<0.05;compared with research group,2)P<0.05.
表2　两组患者临床治疗有效率比较[n(%)]
Tab.2　Comparison of clinical efficacy between two groups[n(%)]
Groups n Cure Significant progress To become better Invalid Total effective rate Research group8621(24.42)54(62.79)9(10.47)2(2.33)75(87.21) Control group8212(14.63)49(59.76)15(18.29)6(7.32)61(74.39) Z/χ22.38394.473
P0.01710.034
表3　两组患者免疫功能相关评价指标比较(x±s)
Tab.3　Comparison of related immune function evaluation indicators between two groups(x±s)
Groups n Measuring time IgA(g/L)IgG(g/L)IgM(g/L)TNF⁃α(ng/L)IL⁃6(ng/L)IL⁃1β(ng/L) Research group86Before treatment1.54±0.297.86±1.730.95±0.4656.78±7.5643.09±7.5751.17±7.46 After treatment0.62±0.181)6.64±1.431)0.67±0.281)28.62±5.411)22.60±4.801)23.94±4.081) Control group82Before treatment1.58±0.317.79±1.761.02±0.5057.20±7.3143.52±7.6350.86±7.24 After treatment0.78±0.171)2)7.01±1.541)2)0.78±0.311)2)31.75±5.681)2)26.74±4.911)2)26.60±4.131)2) Note:Compared with the same group before treatment,1)P<0.05;compared with research group,2)P<0.05.
2.3　两组患者TESS评分比较　研究组TESS评分为(
3.79±1.15)分,对照组TESS评分为(
4.53±
1.20)分,两组比较差异有统计学意义(t= 4.081,P<0.001)㊂
2.4　两组患者免疫功能相关评价指标比较　治疗前,两组患者IgA㊁IgG㊁IgM和TNF⁃α㊁IL⁃6㊁IL⁃1β水平比较,差异均无统计学意义(P>0.05);治疗后,研究组IgA㊁IgG㊁IgM水平均明显低于对照组(P< 0.05);且研究组TNF⁃α㊁IL⁃6㊁IL⁃1β水平也明显低于对照组(P<0.05),见表3㊂
3　讨论
精神分裂症是一种常见的精神障碍性疾病,患者在认知㊁情感㊁思维㊁行为等多个方面的精神活动存在异常,且难以预测病情及症状波动状况,临床治疗难度较大,目前还缺乏完全有效㊁毒副作用小的理想治疗药物㊂临床上治疗精神分裂症的西药分为典型和非典型精神病药两大类,以利培酮㊁氯氮平㊁阿立哌唑㊁奥氮平为代表的非典型抗精神病药在疗效㊁耐受性㊁安全性等多方面均优于典型抗精神病药,但仍存在一定的局限性,对慢性迁延病程患者疗效不佳,易产生高血压㊁高血脂㊁体重增加等副作用[8,9]㊂研究发现,中药治疗精神分裂症,可对机体进行多靶点㊁多器官㊁多系统地综合作用,且毒副作用小,可长程治疗,并达到提高治疗效率,降低不良反应的目的[10]㊂
精神分裂症为现代医学的病名,在中医古籍中未提及,根据其病症应属中医学 癫狂”之范畴㊂中医认为,其病因包括痰气上扰㊁阴阳失调㊁七情内伤㊁
气血凝滞等,癫狂病位在心,与肝㊁脾相关,癫证病因
以痰气郁结㊁痰火交结为主,狂证病因以肝郁化火㊁
气滞血瘀为主,辨证治疗应围绕 痰㊁气㊁火㊁淤”方
面,尤以治 痰”为主[11,12]㊂温胆汤是一味疗效确切的化痰经典方,具有清胆和胃㊁除痰止呕之功效,宁
神温胆汤在温胆汤基础上增加了酸枣仁㊁石菖蒲两
味㊂温胆汤原方由伏苓㊁半夏㊁竹茹㊁枳实㊁陈皮㊁甘
草㊁生姜㊁大枣组成,其中茯苓可益脾和胃㊁宁心安
神;半夏可燥湿化痰㊁降逆止呕;竹茹可清热化痰㊁除
烦止呕;枳实可破气消积㊁化痰散痞;陈皮可芳香化
湿㊁舒畅气机;甘草可补脾益气㊁清热解毒;生姜可解
表散寒㊁温中止呕;大枣补脾和胃㊁益气生津㊂以上
诸药合用可理气化痰㊁清胆和胃,以理气解郁法舒畅
气机,调整脏腑功能㊂酸枣仁具有宁心安神㊁敛汗生
津之功效,主治惊悸怔忡㊁虚烦不眠等症;石菖蒲具
有开窍豁痰㊁醒神益智之功效,主治惊厥㊁癫痫等
症[13,14]㊂因此,酸枣仁和石菖蒲的加入,可增加宁神益志的功效㊂本研究结果也显示,治疗后研究组PANSS总分㊁阳性症状和阴性症状评分均明显降低,且明显低于对照组㊂结果还显示,相较于采用利培酮治疗的患者,采用宁神温胆汤联合利培酮治疗临床有效率更高,TESS评分更低,说明宁神温胆汤联合利培酮治疗精神分裂症临床效果显著,且能够有效控制副反应的发生㊂
本研究结果还显示,本宁神温胆汤联合利培酮
治疗后可明显降低免疫球蛋白IgA㊁IgG㊁IgM水平和
免疫细胞因子TNF⁃α㊁IL⁃6㊁IL⁃1β水平㊂免疫球蛋
白是B细胞膜上的抗原受体,能特异性识别抗原分子,当机体免疫功能损伤时,免疫球蛋白水平则会明显升高;当机体免疫功能逐渐恢复时,免疫球蛋白水平则会相应降低㊂TNF⁃α㊁IL⁃6㊁IL⁃1β均为促炎症性细胞因子,可启动炎性反应,TNF⁃α可参与中枢神经系统炎性反应,释放炎症介质,加重疾病症状;IL⁃
6可激活神经胶质细胞和星形细胞,促进其他细胞因子生成;IL⁃1β是由活化的单核巨噬细胞产生,可激活多种炎症细胞[15]㊂免疫失调会对神经递质㊁神经变性及神经发育等多方面产生影响,众多炎症因子可减少神经元增殖,降低神经元连接性,最终导致脑组织损伤,加重精神分裂症阳性㊁阴性症状[16]㊂宁神温胆汤可抑制TNF⁃α㊁IL⁃6㊁IL⁃1β促炎症性细胞因子的表达,发挥抗炎作用,改善患者免疫功能,从而达到治疗精神分裂症的目的㊂
综上所述,宁神温胆汤联合利培酮疗效确切,可明显改善患者精神状况及免疫功能,值得临床推广㊂参考文献:
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[收稿2018⁃12⁃18　修回2019⁃01⁃21]
(编辑　刘咸筠)。