基于“虚、瘀、毒”病机理论的膝痹病病证结合模型的建立及评价

Establishment and evaluation of a combination of disease and syndrome model of knee osteoarthritis based on the pathogenesis theory of“Deficiency,Stasis,and Toxicity”

目的基于膝骨关节炎(knee osteoarthritis,KOA)“虚、瘀、毒”病机理论,探讨KOA病证结合模型的建模方法。方法将24只新西兰大白兔随机分为正常对照(SHAM)组、KOA模型(MODEL)组、KOA病症结合模型(TCM+MODEL)组,每组8只。SHAM组正常喂养;MODEL组采用石膏固定法建立KOA模型;TCM+MODEL组在石膏固定法的基础上,联合氢化可的松灌胃和中医病因因素(风、寒、湿)干预。造模6周后,对各组动物进行综合评价,包括中医证候及体征评分、膝关节影像学、关节面大体观察、番红O-固绿染色、血液及关节液IL-6和TNF-α表达水平、血液流变学、血清皮质醇(CORT)、睾酮(T)、超氧化物歧化酶(SOD)、丙二醛(MDA)表达水平。结果TCM+MODEL组兔在中医症候及体征评分、影像学评分、大体观察评分、Mankin评分、关节液中IL-6、TNF-α表达水平、血液流变学指标中的血浆黏度(PV)和红细胞聚集指数(RCAI)、血清MDA方面,均明显高于SHAM组和MODEL组(P<0.05);与MODEL组比较,TCM+MODEL组血清CORT、T、SOD明显降低(P<0.05),而血清IL-6、TNF-α含量无明显差异(P>0.05)。结论采用石膏固定法,再结合以氢化可的松灌胃的肾虚证造模方式和中医风、寒、湿病因干预,可复制出具有“虚、瘀、毒”病机特点的KOA病证结合模型,为进一步开展中医药对膝痹病的辨证论治研究提供实验基础。

Objective To explore a modeling method of the combination of disease and syndrome of knee osteoarthritis KOA based on the pathogenesis theory of“Deficiency,Stasis and Toxicity”in(KOA).Methods Overall,24 New Zealand white rabbits were randomly divided into a SHAM group(n=8),MODEL group(n=8),and TCM+MODEL group(n=8).The SHAM group was fed normally.The MODEL group was established by plaster fixation.In the TCM+MODEL group,we hydrocortisone gavage and TCM etiological factors(wind,cold,and wet)were combined based on plaster fixation.After 6 weeks of modeling,each group was comprehensively evaluated,including the TCM syndrome and sign score,knee imaging,articular surface gross observation,Saffron O-solid green staining,blood and articular fluid IL-6 and TNF-α levels,hemorheology,and serum CORT,T,SOD,and MDA levels.Results The TCM symptom and sign score,imaging score,gross observation score,Mankin score,levels of IL-6 and TNF-α in joint fluid,hemorheology indexes(PV and RCAI),and serum MDA in the TCM+MODEL group were significantly higher than those in SHAM and MODEL groups(P<0.05).Compared with the MODEL group,serum CORT,T,and SOD were significantly decreased in the TCM+MODEL group(P<0.05),while serum IL-6 and TNF-α were not significantly different(P>0.05).Conclusions By plaster fixation combined with the model of kidney deficiency syndrome gavage with hydrocortisone and etiological treatment with traditional Chinese medicine,including wind,cold,and wet,we reproduced the combination of disease and syndrome model of KOA with the characteristics of“Deficiency,Stasis and Toxicity”,which provides an experimental basis for further research on syndrome differentiation and treatment of KOA by traditional Chinese medicine.