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《中医正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:

第28卷

期数:

2016年08期

页码:

13-18

栏目:

临床研究

出版日期:

2016-08-20

文章信息/Info

Title:

A clinical study on the curative effect and mechanism of action of external applications of antipyretic-detoxicate traditional Chinese drugs for treatment of traumatic infected wounds

作者:

杨洪杰; 周利; 吴海红; 胡纪文

广东省深圳市罗湖区中医院,广东 深圳 518001

Author(s):

YANG Hongjie; ZHOU Li; WU Haihong; HU Jiwen

Luohu Hospital of Traditional Chinese Medicine,Shenzhen 518001,Guangdong,China

关键词:

清热解毒药;  中药外敷;  呋喃西林;  伤口感染;  Toll样受体4;  肿瘤坏死因子α;  白细胞介素1β;  白细胞介素6;  临床试验

Keywords:

antipyretic-detoxicate drugs;  external applications(TCD);  nitrofurazone;  wound infection;  toll-like receptor 4;  tumor necrosis factor-alpha;  interleukin-1 beta;  interleukin-6;  clinical trial

摘要:

目的:观察清热解毒中药外敷治疗外伤感染创面的疗效并探讨其作用机制。方法:将100例外伤感染创面患者随机分为2组,每组50例,分别采用清热解毒中药外敷和呋喃西林外敷治疗,连续治疗至创面愈合。比较治疗前及治疗第7天和第14天2组患者感染创面面积、外周血单个核细胞表面Toll样受体4(toll-like receptor 4,TLR4)的表达情况及外周血血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1 beta,IL-1β)、白细胞介素6(interleukin-6,IL-6)的表达情况,并于治疗开始后2周比较2组患者的临床疗效。结果:清热解毒中药组的感染创面愈合时间短于呋喃西林组[(16.10±3.15)d,(18.26±3.72)d, t=3.133,P=0.002]。治疗前后不同时间点感染创面面积比较,差异有统计学意义,存在时间效应,治疗后创面面积逐渐缩小(F=13.250,P=0.002); 2组患者感染创面面积比较,差异有统计学意义,存在分组效应(t=2.040,P=0.044); 治疗前2组患者感染创面面积比较,差异无统计学意义[(12.80±1.61)cm²,(13.00±2.21)cm²,t=0.517,P=0.606]; 治疗第7天和第14天清热解毒中药组的感染创面面积均小于呋喃西林组[(6.50±0.97)cm²,(8.30±0.94)cm²,t=9.422,P=0.000;(3.00±0.66)cm²,(5.70±0.67)cm²,t=20.300,P=0.000]; 时间因素与分组因素存在交互效应(F=6.830,P=0.003)。治疗前后不同时间点TLR4表达量比较,差异有统计学意义,存在时间效应,治疗后TLR4表达量逐渐减少(F=6.864,P=0.017); 2组患者TLR4表达量比较,差异有统计学意义,存在分组效应(t=2.185,P=0.031); 治疗前2组患者TLR4表达量比较,差异无统计学意义[(5.81±0.78)ng·mL^-1,(5.79±0.73)ng·mL^-1,t=0.132,P=0.890]; 治疗第7天和第14天清热解毒中药组的TLR4表达量均低于呋喃西林组[(4.10±0.33)ng·mL^-1,(4.69±0.27)ng·mL^-1,t=9.784,P=0.000;(2.82±0.55)ng·mL^-1,(3.80±0.59)ng·mL^-1,t=8.591,P=0.000]; 时间因素与分组因素存在交互效应(F=6.012,P=0.005)。治疗前后不同时间点TNF-α表达量比较,差异有统计学意义,存在时间效应,治疗后TNF-α表达量逐渐减少(F=38.313,P=0.000); 2组患者TNF-α表达量比较,差异有统计学意义,存在分组效应(t=2.195,P=0.030); 治疗前2组患者TNF-α表达量比较,差异无统计学意义[(97.55±6.27)ng·mL^-1,(97.66±7.07)ng·mL^-1,t=0.082,P=0.934]; 治疗第7天和第14天清热解毒中药组的TNF-α表达量均低于呋喃西林组[(52.46±6.84)ng·mL^-1,(74.10±4.49)ng·mL^-1,t=18.701,P=0.000;(25.72±3.95)ng·mL^-1,(40.43±2.42)ng·mL^-1,t=22.454,P=0.000]; 时间因素与分组因素存在交互效应(F=38.812,P=0.000)。治疗前后不同时间点IL-1β表达量比较,差异有统计学意义,存在时间效应,治疗后IL-1β表达量逐渐减少(F=28.000,P=0.000); 2组患者IL-1β表达量比较,差异有统计学意义,存在分组效应(t=2.361,P=0.020); 治疗前2组患者IL-1β表达量比较,差异无统计学意义[(61.13±5.60)pg·mL^-1,(61.90±5.35)pg·mL^-1,t=0.703,P=0.483]; 治疗第7天和第14天清热解毒中药组的IL-1β表达量均低于呋喃西林组[(31.03±3.06)pg·mL^-1,(38.69±4.40)pg·mL^-1,t=10.106,P=0.000;(12.44±1.36)pg·mL^-1,(21.91±2.05)pg·mL^-1,t=27.210,P=0.000]; 时间因素与分组因素存在交互效应(F=7.431,P=0.002)。治疗前后不同时间点IL-6表达量比较,差异有统计学意义,存在时间效应,治疗后IL-6表达量逐渐减少(F=24.492,P=0.001); 2组患者IL-6表达量比较,差异有统计学意义,存在分组效应(t=2.078,P=0.040); 治疗前2组患者IL-6表达量比较,差异无统计学意义[(127.92±10.51)pg·mL^-1,(123.56±11.45)pg·mL^-1,t=1.983,P=0.050]; 治疗第7天和第14天清热解毒中药组的IL-6表达量均低于呋喃西林组[(52.56±3.59)pg·mL^-1,(68.93±4.88)pg·mL^-1,t=19.106,P=0.000;(31.37±2.37)pg·mL^-1,(42.64±2.89)pg·mL^-1,t=21.324,P=0.000]; 时间因素与分组因素存在交互效应(F=10.670,P=0.000)。治疗开始后2周,采用自拟标准评价临床疗效,清热解毒中药组痊愈27例、显效11例、有效12例,呋喃西林组痊愈12例、显效10例、有效23例、无效5例; 清热解毒中药组的临床疗效优于呋喃西林组(Z=2 026.000,P=0.000)。结论:清热解毒中药外敷治疗外伤感染创面可以减小创面面积、缩短创面愈合时间,其临床疗效优于呋喃西林外敷; 其作用机制可能是通过抑制外周血单个核细胞表面TLR4的表达,使TNF-α、IL-1β及IL-6的表达受到抑制,从而减轻了炎症反应。

Abstract:

Objective:To study the curative effect and mechanism of action of external applications of antipyretic-detoxicate traditional Chinese drugs(TCD)for treatment of traumatic infected wounds.Methods:One hundred patients with traumatic infected wounds were randomly divided into 2 groups,50 cases in each group.The patients were treated with external applications of antipyretic-detoxicate TCD(group A)and nitrofurazone(group B)continuously until the wounds healed.The infected wound areas,the expression of toll-like receptor 4(TLR4)on the surface of peripheral blood mononuclear cell and the expression of tumor necrosis factor-α(TNF-α),interleukin-1 beta(IL-1β)and interleukin-6(IL-6)in peripheral blood serum were compared between the 2 groups before treatment and at the 7th and 14th day after the beginning of the treatment respectively,and the clinical effects were evaluated and compared between the 2 groups at 2 weeks after the begining of treatment.Results:The healing time of infected wounds were shorter in group A compared to group B(16.10+/-3.15 vs 18.26+/-3.72 days,t=3.133,P=0.002).There was statistical difference in the infected wound areas between different timepoints before and after the treatment,in other words,there was time effect,and the wound areas decreased gradually after treatment(F=13.250,P=0.002).There was statistical difference in the infected wound areas between the 2 groups in general,in other words,there was group effect(t=2.040,P=0.044).There was no statistical difference in the infected wound areas between the 2 groups before treatment(12.80+/-1.61 vs 13.00+/-2.21 cm(2),t=0.517,P=0.606).The infected wound areas were smaller in group A compared to group B at the 7th and 14th day after the beginning of the treatment(6.50+/-0.97 vs 8.30+/-0.94 cm(2),t=9.422,P=0.000; 3.00+/-0.66 vs 5.70±0.67 cm(2),t=20.300,P=0.000).There was interaction between time factor and group factor(F=6.830,P=0.003).There was statistical difference in the expression levels of TLR4 between different timepoints before and after the treatment,in other words,there was time effect,and the expression levels of TLR4 decreased gradually after treatment(F=6.864,P=0.017).There was statistical difference in the expression levels of TLR4 between the 2 groups in general,in other words,there was group effect(t=2.185,P=0.031).There was no statistical difference in the expression levels of TLR4 between the 2 groups before treatment(5.81+/-0.78 vs 5.79+/-0.73 ng/ml,t=0.132,P=0.890).The expression levels of TLR4 were lower in group A compared to group B at the 7th and 14th day after the beginning of the treatment(4.10+/-0.33 vs 4.69+/-0.27 ng/ml.t=9.784,P=0.000; 2.82+/-0.55 vs 3.80+/-0.59 ng/ml,t=8.591,P=0.000).There was interaction between time factor and group factor(F=6.012,P=0.005).There was statistical difference in the expression levels of TNF-α between different timepoints before and after the treatment,in other words,there was time effect,and the expression levels of TNF-α decreased gradually after treatment(F=38.313,P=0.000).There was statistical difference in the expression levels of TNF-α between the 2 groups in general,in other words,there was group effect(t=2.195,P=0.030).There was no statistical difference in the expression levels of TNF-α between the 2 groups before treatment(97.55+/-6.27 vs 97.66+/-7.07 ng/ml,t=0.082,P=0.934).The expression levels of TNF-α were lower in group A compared to group B at the 7th and 14th day after the beginning of the treatment(52.46+/-6.84 vs 74.10+/-4.49 ng/ml,t=18.701,P=0.000; 25.72+/-3.95 vs 40.43+/-2.42 ng/ml,t=22.454,P=0.000).There was interaction between time factor and group factor(F=38.812,P=0.000).There was statistical difference in the expression levels of IL-1β between different timepoints before and after the treatment,in other words,there was time effect,and the expression levels of IL-1β decreased gradually after treatment(F=28.000,P=0.000).There was statistical difference in the expression levels of IL-1β between the 2 groups in general,in other words,there was group effect(t=2.361,P=0.020).There was no statistical difference in the expression levels of IL-1β between the 2 groups before treatment(61.13+/-5.60 vs 61.90+/-5.35 pg/ml,t=0.703,P=0.483).The expression levels of IL-1β were lower in group A compared to group B at the 7th and 14th day after the beginning of the treatment(31.03+/-3.06 vs 38.69+/-4.40 pg/ml,t=10.106,P=0.000; 12.44+/-1.36 vs 21.91+/-2.05 pg/ml,t=27.210,P=0.000).There was interaction between time factor and group factor(F=7.431,P=0.002).There was statistical difference in the expression levels of IL-6 between different timepoints before and after the treatment,in other words,there was time effect,and the expression levels of IL-6 decreased gradually after treatment(F=24.492,P=0.001).There was statistical difference in the expression levels of IL-6 between the 2 groups in general,in other words,there was group effect(t=2.078,P=0.040).There was no statistical difference in the expression levels of IL-6 between the 2 groups before treatment(127.92+/-10.51 vs 123.56+/-11.45 pg/ml,t=1.983,P=0.050).The expression levels of IL-6 were lower in group A compared to group B at the 7th and 14th day after the beginning of the treatment(52.56+/-3.59 vs 68.93+/-4.88 pg/ml,t=19.106,P=0.000; 31.37+/-2.37 vs 42.64+/-2.89 pg/ml,t=21.324,P=0.000).There was interaction between time factor and group factor(F=10.670,P=0.000).At 2 weeks after the begining of the treatment,the clinical curative effect were evaluated according to the self-designed therapeutic effect evaluation standard.Twenty-seven patients were cured,11 got a good result and 12 fair in group A; while 12 patients were cured,10 got a good result,23 fair and 5 poor in group B.The group A surpassed the group B in the clinical curative effect(Z=2 026.000,P=0.000).Conclusion:External applications of antipyretic-detoxicate traditional Chinese drugs can reduce the wound area and shorten the wound healing time in the treatment of traumatic infected wounds,and it surpasses the external applications of nitrofurazone in the clinical curative effect.It can inhibit the expression of TNF-α,IL-1β and IL-6 through inhibiting the expression of TLR4 on the surface of peripheral blood mononuclear cells,which may be the mechanisms of action for reducing the inflammatory reaction.

备注/Memo

备注/Memo:

基金项目:深圳市罗湖区科技创新局软科学项目(2015-55)

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更新日期/Last Update: 1900-01-01