苗药五藤膏外敷对膝骨关节炎兔模型的 治疗作用及机制.

Objective　 To investigate the therapeutic effect and mechanism of the external application of Miao medicine Wuteng ointment on rabbit knee osteoarthritis ( KOA). Methods　 Ninety-six rabbits were divided into the blank control group, model group, babu ointment group, low-dose, medium-dose, high-dose Wuteng ointment groups, with 16 rabbits in each group. Except for the blank control group, rabbit KOA cartilage models were established with 4% papain saline solution in the remaining groups. In the 6th week of modeling, the rabbits in the blank control group and the model group were given sterile gauze bandaging and fixation of the right knee joint every day. The rabbits in the low-dose, medium-dose and high-dose groups of Wuteng ointment were given 1, 2 and 4 g of Wuteng plaster in front of the right knee joint of the rabbit. The rabbits in the babu plaster group were given flurbiprofen and the plaster was applied to the front of the right knee joint. All were fixed with bandages for 4 h, administered once a day, and intervened for 4 weeks. Four rabbits were sacrificed in each group at 1, 2, 3, and 4 weeks of administration, and cartilage above the calcified layer at the apex of the right femoral medial condyle was taken. After HE staining, cartilage tissue morphological changes were observed, and the degree of histopathological changes of knee cartilage was evaluated by Mankin's score, and the expression levels of Wnt/β-catenin signaling pathway downstream target genes GSK-3β, MMP-3, OPG and Notch signaling pathway downstream target gene Notch1 in the knee cartilage tissues were detected by qRT-PCR. Results　 The surface of articular cartilage in the blank control group was smooth and flat, and the structure was clear. In the model group, the surface of articular cartilage was rough and uneven, the structure was blurred, the number of chondrocytes was small and the distribution was disordered. The rabbits in the high-dose group of Wuteng ointment had smooth and flat articular cartilage surface, clearer structure, and a larger number of chondrocytes with more uniform distribution. The rabbits in the low-dose and medium- dose groups of Wuteng ointment and the babu ointment group had different degrees of joint swelling and synovial hyperemia, their hierarchy was blurred, the number of chondrocytes was small and the distribution was mildly disordered. Compared with the blank control group, the model group had a high score of Mankin's in the knee cartilage tissues (P< 0. 05). Compared with the model group, the Mankin's score in the treatment group was low (P<0. 05), and the Mankin's score in the high-dose group of Wuteng ointment was the lowest ( P<0. 05). Compared with the blank control group, the expression levels of GSK-3β, MMP-3 and Notch1 mRNA in the knee cartilage tissues were higher in the model group (all P< 0. 05) and the expression of OPG mRNA was lower (P<0. 05). Compared with the model group, GSK-3β, MMP-3 and Notch1 mRNA expression levels were lower (all P<0. 05) and OPG mRNA expression was higher (P<0. 05), and the above index changes were the most significant in the high-dose group of Wuteng ointment (all P<0. 05). Conclusion　 Miao medicine Wuteng ointment can improve knee cartilage and subchondral lesions and delay the progression of the disease in KOA rabbits, and its mechanism may be related to the regulation of downstream target genes of Wnt/β-catenin and Notch signaling pathways [ABSTRACT FROM AUTHOR]