【目的】 观察恒古骨伤愈合剂口服联合定向透药治疗寒湿痹阻型膝骨关节炎（KOA）的临床疗效。【方法】 将2022年9月至 2023年9月于湖南省中西医结合医院就诊的120例寒湿痹阻型KOA患者按随机数字表法随机分为对照组、口服组、药透组和 联合组，每组各30例。其中，对照组给予塞来昔布胶囊口服治疗，口服组给予恒古骨伤愈合剂口服治疗，药透组给予恒古 骨伤愈合剂定向透药治疗，联合组给予恒古骨伤愈合剂口服联合定向透药治疗。以 12 d为 1个疗程，均连续治疗 2个疗程。 观察各组患者治疗前后中医证候积分、疼痛视觉模拟量表（VAS）评分、西安大略和麦克马斯特大学骨关节炎指数（WOMAC） 评分、生活质量健康调查简表（SF-36）评分以及血清白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α） 水平的变化情况，并评价各组患者的临床疗效与用药安全性。【结果】（1）疗效方面，治疗2个疗程后，联合组的总有效率为 96.67%（29/30），高于对照组的 73.33%（22/30）及口服组和药透组的 70.00%（21/30），组间比较，差异均有统计学意义（P < 0.05）；而对照组、口服组及药透组的总有效率比较，差异均无统计学意义（P > 0.05）。（2）中医证候、疼痛程度和关节功能方 面，治疗后，4组患者的中医证候积分、疼痛 VAS评分和 WOMAC评分均较治疗前降低（P < 0.01）；组间比较，联合组的中 医证候积分、疼痛VAS评分和WOMAC评分均明显低于对照组、口服组及药透组（P < 0.05），而对照组、口服组及药透组的 中医证候积分、疼痛 VAS评分和 WOMAC评分比较，差异均无统计学意义（P > 0.05）。（3）生活质量方面，治疗后，4组患者 SF-36的生理功能（PF）、躯体疼痛（BP）、一般健康（GH）、精力（VT）、生理职能（RP）、社会功能（SF）、情感职能（RE）以及 精神健康（MH）等各维度评分均较治疗前明显提高（P < 0.01）；组间比较，联合组的SF-36各维度评分均明显高于对照组、口 服组及药透组（P < 0.05），而对照组、口服组及药透组的SF-36各维度评分比较，差异均无统计学意义（P > 0.05）。（4）血清炎 症因子方面，治疗后，4组患者的血清IL-1β、IL-6、TNF-α水平均较治疗前下降（P < 0.01）；组间比较，联合组血清IL-1β、 IL-6、TNF-α水平的下降幅度均明显优于对照组、口服组及药透组（P < 0.05），对照组、口服组的下降幅度又均优于药透组 （P < 0.05），而对照组与口服组比较，差异均无统计学意义（P > 0.05）。（5）安全性方面，研究过程中，4组患者均未出现严重 不良反应，具有较高的安全性。【结论】 恒古骨伤愈合剂内外联动特色疗法能有效改善寒湿痹阻型KOA患者的关节疼痛、功 能以及生活质量，起到加速康复的作用，其疗效机制可能与降低炎症因子表达水平有关。

Objective To observe the clinical efficacy of oral use combined with targeted transdermal delivery of Osteoking in treating knee osteoarthritis（KOA）of cold-damp blockage type. Methods A total of 120 patients with KOA of cold-damp blockage type who admitted to Hunan Provincial Hospital of Integrated Traditional Chinese And West Medicine from September 2022 to September 2023 were randomly divided into the control group，oral use group，transdermal delivery group and combination group according to the random number table method，with 30 cases in each group. The control group was treated with Celecoxib Capsule orally，the oral use group was treated with Osteoking orally，the transdermal delivery group was treated with Osteoking by targeted transdermal delivery， and the combination group was treated with oral use combined with targeted transdermal delivery of Osteoking. One course of treatment covered 12 days，and all of the four groups were treated for two continuous courses. Before and after treatment，the scores of traditional Chinese medicine（TCM）syndrome，Visual Analogue Scale（VAS）for pain， Western Ontario and McMaster Universities Osteoarthritis Index（WOMAC）for joint function， 36-Item Short Form Health Survey（SF-36）for quality of life（QOL），as well as the levels of serum interleukin 1β（IL-1β）， interleukin 6（IL-6），and tumor necrosis factor α（TNF - α）were observed in the patients of each group. After treatment，the clinical efficacy and safety of patients in each group were evaluated. Results（1）After two courses of treatment，the total effective rate of the combination group was 96.67%（29/30），which was higher than those of the control group [73.33%（22/30）]，oral use group and transdermal delivery group [both being 70.00%（21/30）] ， and the difference was statistically significant（P < 0.05）. However，no statistically significant difference of the total effective rate was presented among the control group，oral use group，and transdermal delivery group（P > 0.05）. （2）After treatment，the scores of TCM syndrome，VAS for pain and WOMAC for joint function in the four groups were decreased compared with those before treatment（P < 0.01）. The intergroup comparison showed that the scores of TCM syndrome，VAS for pain and WOMAC in the combination group were lower than those in the other three groups（P < 0.05），while no statistically significant difference of the scores of TCM syndrome，VAS for pain and WOMAC were presented among the control group，oral use group，and transdermal delivery group（P > 0.05）.（3）After treatment，the QOL scores of the eight dimensions of SF-36 such as physical functioning（PF），bodily pain（BP）， general health（GH），vitality（VT），role-physical（RP），social functioning（SF），role-emotional（RE），and mental health（MH）in the four groups were significantly increased compared with those before treatment（P < 0.01）. The intergroup comparison showed that the scores of each dimension of SF-36 in the combination group were significantly higher than those in the other three groups（P < 0.05），while no statistically significant difference of the dimension score of SF-36 was presented among the control group，oral use group，and transdermal delivery group（P > 0.05）.（4）After treatment，the levels of serum inflammatory factors of IL-1β，IL-6，and TNF-α in the four groups were decreased compared with those before treatment（P < 0.01）. The intergroup comparison showed that the decrease of serum levels of inflammatory factors in the combination group were significantly superior to those in the other three groups（P < 0.05），and the decrease in the control group and oral use group were all superior to those in the transdermal delivery group（P < 0.05），while the difference between the control group and oral use group was not statistically significant（P > 0.05）.（5）During the trial， no serious adverse reactions were found in the patients of four groups，which is of high safety. Conclusion Oral use combined with targeted transdermal delivery of Osteoking is effective on improving the joint pain， joint function and QOL of patients with KOA of cold-damp blockage type，and can speed up the rehabilitation of patients. Its therapeutic mechanism may be related to the decrease of the expression level of inflammatory factors.

R274.9

中国博士后科学基金面上项目（编号：2023M731070）；湖南省自然科学基金项目（编号：2023JJ60118）；长沙市科技局重点项目 （编号：kh2201063）；湖南省中医药研究院院级科研项目（编号：202129）