摘要
目的探讨膝痹方对膝骨关节炎血瘀证大鼠软骨的保护作用。方法采用肾上腺素注射+冰水应激法建立血瘀证模型,木瓜蛋白酶联合L-半胱氨酸注射法诱导膝骨关节炎模型,造模成功大鼠依据随机数字表随机分为模型组、阳性组和膝痹方高、低剂量组,每组8只,另取大鼠8只,不做造模干预,仅注射及灌胃等体积生理盐水,作为正常组。模型组和正常组灌胃等体积生理盐水,膝痹方高、低剂量组按体表面积换算,分别灌胃50、25 g/kg膝痹方水煎液,阳性组灌胃50 mg/kg双醋瑞因,各组均每天给药1次,持续6周。观察并记录给药前后各组大鼠的整体体征,测量造模后及给药2、4、6周后的膝关节肿胀度;检测血液流变学指标,包括全血黏度、血浆黏度和红细胞聚集指数;HE染色法观察关节软骨组织病理变化并进行Mankin′s评分;RT-q PCR法检测软骨Ⅱ型胶原α1链(CⅡα1)、聚蛋白聚糖(Acan)、寡聚基质蛋白(Comp)的基因表达情况。结果与模型组比较,膝痹方高、低剂量组可改善膝骨关节炎血瘀证大鼠的血瘀证候,全血黏度、血浆黏度及红细胞聚集指数显著降低(P<0.01,P<0.05);膝痹方高剂量组给药4、6周后的膝关节肿胀度显著降低(P<0.05,P<0.01),膝痹方低剂量组给药6周后的膝关节肿胀度显著降低(P<0.01);膝痹方高、低剂量组可改善关节软骨结构受损、软骨细胞紊乱等病理现象,Mankin′s评分亦显著降低(P<0.01,P<0.05);膝痹方高、低剂量组可显著上调关节软骨CⅡα1、Acan、Comp相对基因表达量(P<0.01)。与阳性组比较,膝痹方低剂量组CⅡα1、Acan相对基因表达量明显降低(P<0.05)。结论膝痹方可有效改善膝骨关节炎血瘀证大鼠的整体体征和膝关节症状,上调软骨合成代谢相关基因,实现软骨保护的目的。
Objective To investigate the cartilage-protective effects of Xibi Decoction in rats with knee osteoarthritis by syndrome of blood stasis(KOA-BS).Methods The syndrome of blood stasis model was induced through adrenalin injections and ice-water stress method;The knee osteoarthritis model was induced through intra-articular injections of papain and L-cysteine.After modeling,the rats were randomly divided into four groups:model group,positive group,Xibi Decoction high-dose group and Xibi Decoction low-dose group,with eight rats in each group.Another 8 rats were selected as the normal group,without any modeling intervention,and only injected and gavaged with the equal volume of physiological saline.The model group and normal group were gavaged with the equal volume of physiological saline.According to the rats'body surface area,the Xibi Decoction high-dose group were gavaged with 50 g/kg of Xibi Decoction,while the Xibi Decoction low-dose group were gavaged with 25 g/kg of Xibi Decoction,the positive group were gavaged with 50 mg/kg of diacerein.Each group were administered once per day for six weeks.The overall psychical signs of the rats in each group were monitored and recorded before and after the treatment.Knee joint swelling were measured before treatment and at 2,4 and 6 weeks post-treatment.Blood rheology indicators were assessed including the plasma viscosity,whole blood viscosity,and erythrocyte aggregation index.Histopathological evaluations of articular cartilage were conducted through HE staining and scored by Mankin's scoring system.Additionally,gene expression levels of collagen typeⅡα1 chain(CⅡα1),aggrecan(Acan),and Cartilage Oligomeric Matrix Protein(Comp)were analyzed by the RT-qPCR method.Results The rats in the high-and low-dose groups showed improvement in knee osteoarthritis by syndrome of blood stasis,with significant reductions in plasma viscosity,whole blood viscosity,and erythrocyte aggregation index compared with the model group(P<0.01,P<0.05).Knee joint swelling was significantly reduced in the high-dose group after 4 and 6 weeks of treatment(P<0.05,P<0.01),and in the low-dose group,the knee joint swelling was significantly reduced after 6 weeks(P<0.01).The rats in highand low-dose groups exhibited improvements in the flatness of the articular cartilage surface,structural integrity,and arrangement of chondrocytes,with Mankin's scores significantly lower(P<0.01,P<0.05).Additionally,both treatment groups significantly upregulated the relative gene expression of articular cartilage CIIα1,Acan,and Comp(P<0.01).Compare with the positive group,the relative gene expression levels of CIIα1 and Acan were significantly reduced in the low-dose group(P<0.05).Conclusion Xibi Decoction demonstrates efficacy in ameliorating the overall clinical signs and knee joint symptoms in KOA-BS rats.It also promotes the upregulation of genes related to cartilage anabolism,thereby contributing to cartilage protection.
作者
张上
杨军
冯丽娜
刘炳君
ZHANG Shang;YANG Jun;FENG Lina;LIU Bingjun(Henan Provincial Corps Hospital of Chinese People's Armed Police Force,Zhengzhou 450000,China;Henan Province Hospital of TCM/The Second Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450011,China)
出处
《中医药信息》
2026年第2期47-52,共6页
Information on Traditional Chinese Medicine
基金
河南省中医药科学研究专项课题项目(24ZY1013)。
关键词
膝痹方
膝骨关节炎
血瘀证
大鼠
软骨保护
Xibi Decoction
Knee osteoarthritis
Syndrome of blood stasis
Rat
Cartilage protection
