虎符铜砭刮痧治疗尿毒症皮肤瘙痒的效果及其对C反应蛋白和白细胞介素-6水平的影响.pdf

2023,43(6)http:/J Clin Pathol Res 临床与病理杂志虎符铜砭刮痧治疗尿毒症皮肤瘙痒的效果及其对C反应蛋白和白细胞介素-6水平的影响邓彩春，曾翠青，黄日珍，徐媛（海南省中医院肾病风湿科，海口 570203）摘要 目的：探讨虎符铜砭刮痧治疗尿毒症皮肤瘙痒的疗效及其对C反应蛋白(C-reactive protein，CRP)和白细胞介素-6(interleukin-6，IL-6)水平的影响。方法：选取2022年1月至2022年9月海南省中医院收治的100例尿毒症皮肤瘙痒患者为研究对象，按随机数字表法随机分为对照组与观察组，每组各50例。对照组予以常规基础治疗，观察组在对照组基础上增加虎符铜砭刮痧治疗。评估2组临床疗效，并比较治疗前后改良Dou氏瘙痒量表评分、生活质量评估量表(Short Form 36 Questionnaire，SF-36)评分、尿素下降率(urea reduction rate，URR)、单室尿素清除指数(single-compartment urea clearance index，spKt/V)及血清CRP、IL-6、磷(phosphorus，P)、钙(calcium，Ca)、血肌酐(serum creatinine，SCr)、甲状旁腺激素(parathyroid hormone，PTH)水平。结果：观察组临床总有效率明显高于对照组(分别为92.00%和70.00%，P0.05)。与对照组相比，观察组改良Dou氏瘙痒量表评分较低，SF-36评分较高(均P0.05)。治疗后，观察组血清CRP、IL-6、P、PTH水平均明显低于对照组(均P0.05)。结论：虎符铜砭刮痧治疗尿毒症皮肤瘙痒具有良好的疗效和安全性，可有效缓解患者瘙痒症状，改善其生活质量，并降低血清P、PTH及炎症因子CRP、IL-6水平，这可能是其疗效的作用机制。关键词 虎符铜砭刮痧；皮肤瘙痒；尿毒症；血液透析；C反应蛋白；白细胞介素-6Effect of Hufu copper board scraping therapy on uremic skin pruritus and its effect on C-reactive protein and interleukin-6 levelsDENG Caichun,ZENG Cuiqing,HUANG Rizhen,XU Yuan(Department of Nephrology and Rheumatology,Hainan Provincial Hospital of Traditional Chinese Medicine,Haikou 570203,China)DOI：10.11817/j.issn.2095-6959.2023.222562收稿日期(Date of reception)：2022-12-01第一作者(First author)：邓彩春，Email:,ORCID:0000-0001-7203-5702通信作者(Corresponding author)：邓彩春，Email:,ORCID:0000-0001-7203-5702基金项目(Foundation item)：海南省卫生健康行业科研项目(21A200404)。This work was supported by the Hainan Health Industry Scientific Research Project,China(21A200404).1213临床与病理杂志,2023,43(6)http:/ABSTRACT Objective:To explore the curative effect of Hufu copper board scraping in the treatment of uremic skin pruritus and its effect on the levels of C-reactive protein(CRP)and interleukin-6(IL-6).Methods:A total of 100 patients with uremic skin pruritus who were admitted to Hainan Provincial Hospital of Traditional Chinese Medicine from January 2022 to September 2022 were selected and randomly divided into a control group and an observation group according to the random number table method,with 50 cases in each group.The control group was given routine basic treatment,and the observation group was added with Hufu copper board scraping therapy on the basis of the control group.The clinical efficacy was evaluated between the 2 groups,and the scores of the modified Dou itch scale,Short Form 36 Questionnaire(SF-36),urea reduction rate(URR),single-compartment urea clearance index(spKt/V),and the levels of serum CRP,IL-6,phosphorus(P),calcium(Ca),serum creatinine(SCr),and parathyroid hormone(PTH)between the 2 groups before and after the treatment were compared.Results:The total effective rate of the observation group was significantly higher than that of the control group(92.00%vs 70.00%,P0.05).Compared with the control group,the modified Dou s pruritus scale scores in the observation group were lower after the treatment,and the SF-36 score was higher(both P0.05).After the treatment,the levels of serum CRP,IL-6,P,and PTH in the observation group were significantly lower than those in the control group(all P0.05).Conclusion:Hufu copper board scraping has good efficacy and safety in the treatment of uremic skin pruritus.It can effectively relieve the itching symptoms of patients,improve their quality of life,and reduce serum P,PTH,and inflammatory factors CRP,and IL-6 levels,which may be the mechanism of its efficacy.KEY WORDS Hufu copper board scraping;skin itching;uremia;hemodialysis;C-reactive protein;interleukin-6皮肤瘙痒是尿毒症常见并发症，可导致患者失眠、皮肤感染等，严重影响其生活质量1。维持性血液透析(maintenance hemodialysis，MHD)是尿毒症常用治疗手段，可有效延长患者生存期。但研究2发现：18%28%的MHD患者有不同程度的皮肤瘙痒症状，随着透析次数的增加，患者皮肤瘙痒发生率增高，程度加重。尿毒症皮肤瘙痒的病因尚不明确，可能与皮肤干燥、系统性炎症反应、继发性甲状旁腺功能亢进等因素有关，且目前临床尚无特效治疗方案3。西医常以抗组胺药物、皮肤外用药物治疗，但因作用机制单一疗效有限4；而中药汤剂虽可行多机制、多靶点治疗，但不适用于需严格控制摄入水分的MHD患者。刮痧是中医传统外治之法，其以中医经络腧穴为理论指导，可通过刺激相关穴位、经络促进气血运行，达到益气扶正、祛邪排毒等防病治病的目的5。虎符铜砭刮痧则是利用特制的黄铜刮痧板进行刮痧治疗，由于黄铜可与人体达成最优的共振频率、升高刮试部位温度，其穿透力较普通刮痧效果更强。已有研究6-7证实高血压、肝硬化等疾病患者经虎符铜砭刮痧治疗后均有明显获益。基础研究8显示：刮痧可以扩张皮肤组织的毛细血管，引起红细胞外渗，加速局部微循环，并可引起全身性的免疫活性细胞比例上升，产生治疗效果。余榕等9研究也指出耳穴铜砭刮痧治疗对尿毒症皮肤瘙痒具有缓解作用。基于此，本研究旨在探讨虎符铜砭刮痧治疗尿毒症性皮肤瘙痒的疗效，为临床研究提供一定参考。1214虎符铜砭刮痧治疗尿毒症皮肤瘙痒的效果及其对C反应蛋白和白细胞介素-6水平的影响 邓彩春，等1 对象与方法 1.1 对象本研究符合伦理，且通过海南省中医院(以下简称“本院”)医学伦理委员会批准(审批号：HNSZYY-2021-LL-020)。选取2022年1月至2022年9月本院收治的100例尿毒症皮肤瘙痒患者为研究对象。纳入标准：1)确诊为尿毒症，且符合顽固性皮肤瘙痒诊断标准10；2)于本院行MHD治疗，每周23次，规律治疗时间6个月；3)年龄18岁；4)意识清楚，生命体征稳定，可配合完成相关治疗、护理；5)知情自愿参与研究，且同意随机分组；6)近6个月内无细胞毒性类或激素类药物治疗史；7)近3个月内无感染性疾病、活动性免疫疾病病史。排除标准：1)合并严重心脑血管疾病、肝功能障碍、血液系统疾病；2)因其他原因所致皮肤瘙痒；3)合并严重心理疾病、精神疾病；4)接受甲状旁腺切除术治疗。因患者主动要求退出研究、因其他并发症死亡及发生严重不良反应需立即退出者均已剔除。将入组患者按随机数字表法随机分为对照组与观察组，每组各50例。1.2 治疗方法对照组予以常规基础治疗：1)MHD治疗，仪器为GAMBO AK96、ARTIS CN、BRAUN Dialog710500R、威高DBB-06S等型号血液透析机，选择标准碳酸氢盐透析液、低分子肝素钠抗凝，控制透析液流量为500 mL/min、血流量为220280 mL/min，每次4 h，每周 23 次。2)控制血糖、血压，纠正贫血。3)口服抗组胺药物。4)做好自我护理管理，包括清淡饮食、适度活动、保持情绪舒缓、皮肤护理等。观察组在对照组基础上增加虎符铜砭刮痧治疗，工具为虎符铜砭刮痧板，蘸取适量刮痧油后保持刮痧板与皮肤呈45进行刮试，刮试时尽可能保持均匀的速度和力度。首先，开四阳，刮大椎、大杼、膏肓、神堂；其次，刮透心经、心包经(以大陵、曲泽、曲池、劳宫、左心包、右尺泽为重点穴位)，肺经、大肠经，手三阳经、三阴经；再次，刮透颈项及后枕区，风府至大椎，风池至肩井；随后，开阳脉，刮督脉和膀胱经，刮肝、脾、肾脏区(以期门、日月、章门、京门为重点穴位)；其次，刮胸腺，至腿部，刮胆经、胃经、脾经、肝经；最后，疏通背部阳脉，利用四井排毒。每7 d行1次刮痧治疗，刮痧注意避开皮损处，以出现痧痕或痧斑为宜(不可强行出痧)，以患者可耐受为度，嘱患者刮痧后30 min内禁吹冷风、洗凉水澡。2组均连续治疗3个月。1.3 观察指标于治疗前后检测2组改良Dou氏瘙痒量表评分、生活质量评估量表(Short Form 36 Questionnaire，SF-36)及血清C反应蛋白(C-reactive protein，CRP)、白细胞介素-6(interleukin-6，IL-6)水平，并观测安全性指标血清磷(phosphorus，P)、钙(calcium，Ca)、血肌酐(serum creatinine，SCr)、甲状旁腺激素(parathyroid hormone，PTH)水平、尿素下降率(urea reduction rate，URR)及单室尿素清除指数(single-compartment urea clearance index，spKt/V)。1.4 疗效评价为降低原始数据失真程度，本研究由未参与治疗的医师进行疗效评价，并对其设盲。参考文献11及中药新药临床研究指导原则(试行)12将临床疗效分为3级。缓解：皮肤无抓痕，白天无瘙痒发生，夜间偶发生瘙痒，但程度明显减轻且不影响睡眠；部分缓解：皮肤无明显抓痕，白天及夜间偶发生瘙痒，但程度明显减轻且不影响正常生活及睡眠；无缓解：症状无改善。以缓解、部分缓解例数之和计算临床总有效率。1.5 统计学处理采用SPSS 24.0统计学软件处理数据。计量资料经检验均满足正态分布，用均数标准差(xs)描述，以独立样本t检验、配对t检验作比较；计数资料用例(%)描述，以2检验、Fisher确切概率法作比较。P0.05，表1)。2.2 临床疗效观察组临床总有效率为92.00%(46/50)，明显高于对照组的70.00%(35/50)，组间比较差异有统计学意义(P0.05，表3)。治疗后，2组改良Dou氏瘙痒量表评分均明显降低，SF-36评分均明显提高(均P0.05)；且与对照组相比，观察组改良Dou氏瘙痒量表评分较低，SF-36评分较高(均P0.05，表 4)。治疗后，2 组血清CRP、IL-6水平均明显下降(均P0.05)；且观察组血清 CRP、IL-6 水 平 均 明 显 低 于 对 照 组(均 P0.05，表4)。表4 2组血清炎症因子水平比较(n=50，xs)Table 4 Comparison of serum inflammatory factors between the 2 groups(n=50,xs)组别观察组对照组tPCRP/(mgL1)治疗前15.375.1215.314.890.0600.952治疗后6.221.78*7.122.46*2.0960.039IL-6/(pgmL1)治疗前3.570.503.550.530.1940.847治疗后2.420.36*3.140.43*9.0780.001与治疗前相比，*P0.05。CRP：C反应蛋白；IL-6：白细胞介素-6。表3 2组改良Dou氏瘙痒量表、SF-36评分比较(n=50，xs)Table 3 Comparison of modified Dou itch scale and SF-36 score between the 2 groups(n=50,xs)组别观察组对照组tP改良Dou氏瘙痒量表评分治疗前29.345.7229.106.030.2040.839治疗后11.242.55*16.713.32*9.2390.001SF-36评分治疗前78.655.8478.966.770.2450.807治疗后104.326.9594.637.246.8270.001与治疗前相比，*P0.05，表5)。治疗后，2组血清P、PTH水平均明显降低(均P0.05)；且观察组血清P、PTH水平均明显低于对照组(均P0.05，表5)。3 讨 论 MHD技术的发展有效延长了尿毒症患者的生存期，而其常见并发症皮肤瘙痒的发生率亦随之上升，严重影响了患者心理健康、睡眠质量及生活质量。有研究13发现严重皮肤瘙痒症是导致尿毒症患者死亡的一项重要因素。因此，探讨改善尿毒症患者皮肤瘙痒症状的有效疗法有重要的临床意义。西医采用抗组胺药物、局部外用药物、充分透析等方式进行治疗虽可在一定程度上缓解瘙痒症状，但整体效果差强人意。中医14认为：该病应归属于“痒风”“隐疹”“血风疮”等范畴，与风、毒、瘀、虚相关。尿毒症患者多数有气血亏虚表现，肌肤失养，生风化燥，遂发为皮肤瘙痒，加之患者脾、肾亏虚难承运化之职，湿度内聚于肌肤，瘙痒更甚，故其病机为血虚生风、湿毒蕴结，应以养血祛风、除湿排毒为治疗原则。虎符铜砭刮痧疗法以通论、整体论、徐而和论、四井排毒论等特色理论为指导，在多种疾病治疗中均取得良好疗效15。本研究发现：观察组加用虎符铜砭刮痧治疗后，其临床总有效率明显高于对照组，且与对照组相比，观察组改良Dou氏瘙痒量表评分较低，SF-36评分较高，表明虎符铜砭刮痧可明显提高常规基础疗法治疗尿毒症性皮肤瘙痒的临床疗效，明显缓解患者瘙痒症状，提高其生活质量，这可能与本研究选取的经脉穴位有关。大椎位于督脉，而督脉在背部正中行走，其脉与手足三阳经、阳维脉多次交会，刮之可通一身之阳气，可扶正祛邪；大杼、膏肓、神堂三穴则属太阳膀胱经，刮之可通调膀胱经气，进而调和五脏六腑；刮左心包、右尺泽可引血下行；刮三焦经可解肝之气郁血瘀；开阳脉可振奋阳气，同刮肝、脾、肾脏区则可同治肝、脾、肾，刮胸腺可增强患者免疫力；最后开四井可迅速排除毒素；共同发挥益气养血、调畅理气、扶正祛邪、祛风除湿之功效，最终缓解瘙痒症状。另外，本研究使用的刮痧板以黄酮为材质，黄酮具有杀菌消毒和强传导性特点，有出痧效果好、疼痛感弱、杀菌的优势16，与刮痧油配合可刺激皮肤，促进腠理开泄，强化排毒化瘀、散风活血之效。免疫炎症假说被认为是尿毒症皮肤瘙痒的一种表5 2组安全性观察指标比较(n=50，xs)Table 5 Comparison of safety observation indexes between the 2 groups(n=50,xs)组别观察组对照组tPP/(mmolL1)治疗前2.410.282.400.240.1920.848治疗后2.220.16*2.300.22*2.0800.040Ca/(mmolL1)治疗前2.340.352.370.370.4170.678治疗后2.260.272.290.280.5450.587PTH/(pgmL1)治疗前412.50102.45403.2696.140.4650.643治疗后342.5942.47*368.7471.25*2.2290.028组别观察组对照组tPSCr/(molL1)治疗前1 258.34150.421 241.06138.230.5980.551治疗后1 204.56164.791 213.42175.840.2600.795URR/%治疗前69.316.5369.046.870.2010.841治疗后70.734.9570.324.630.4280.670spKt/V治疗前1.360.221.370.200.2380.813治疗后1.480.191.420.201.5380.127与治疗前相比，*P0.05。P：磷；Ca：钙；PTH：甲状旁腺激素；SCr：血肌酐；URR：尿素下降率；spKt/V：单室尿素清除指数。1217临床与病理杂志,2023,43(6)http:/发病机制。研究17显示：该类患者免疫系统中-干扰素及CXC趋化性细胞因子受体3的表达较无瘙痒患者明显较高，且其血清中CRP、IL-6水平也明显增高，因此认为尿毒症瘙痒的发生以系统性炎症反应为本质，而非局部皮肤病。蒋娟娟等18研究发现：治疗后血清炎症因子IL-6、超敏CRP水平低的患者的皮肤瘙痒症状改善更显著。本研究发现：观察组治疗后血清CRP、IL-6水平均明显低于对照组，表明虎符铜砭刮痧可明显降低尿毒症皮肤瘙痒患者的炎症反应水平。这可能是因为：1)刮痧可使皮肤呈现瘀血和充血状态，该状态可诱发局部毛细血管内电解质分布、浓度的改变，进而加快淋巴循环、血液交换，利用受损组织修复的过程发挥促进毒素排泄、炎症物质吸收的作用19；2)在刮痧后机体的恢复过程中，吸收瘀血的生理过程可持续刺激刮试部位腧穴和经络，维持机体的兴奋性而延长治疗效果20。这可能也是本研究中观察组治疗后血清P、PTH水平均明显低于对照组的原因。另外，在本研究中，2组血清Ca、SCr水平、URR及spKt/V比较差异均无统计学意义，表明虎符铜砭刮痧不会引起P、Ca代谢失调、甲状旁腺功能紊乱等，影响患者MHD治疗的安全性。综上所述，对于尿毒症皮肤瘙痒，虎符铜砭刮痧治疗可明显提高临床疗效，有效缓解患者瘙痒症状，改善其生活质量，降低血清P、PTH及炎症因子CRP、IL-6水平可能是其疗效的作用机制。但本研究仍存在不足之处：首先，由于本院收治病例数及纳入排除标准的限制，最终进入分析的样本量较小，结果可能存在一定偏倚；其次，未对患者进行长期随访。未来仍需前瞻性、大样本研究对结论进行验证和完善。利益冲突声明：作者声称无任何利益冲突。参考文献1陈宗英,谢席胜.尿毒症性皮肤瘙痒研究现状J.中国中西医结合肾病杂志,2017,18(9):841-843.https:/doi.org/10.3969/j.issn.1009-587X.2017.09.034.CHEN 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