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BACKGROUND: Angiogenesis is involved in the progression of early-stage knee osteoarthritis. Synovium, cartilage and subchondral bone all have pathological manifestations of angiogenesis. To explore the inhibitory ability and related pathways of ligustrazine and overexpression of miR-20b-5p on pathological angiogenesis in these tissues will help to develop new drugs for the treatment of early-stage knee osteoarthritis. OBJECTIVE: To investigate the effects of ligustrazine and overexpression of miR-20b-5p on synovial, cartilage and subchondral bone angiogenesis in rats with early-stage knee osteoarthritis. METHODS: Twenty-five Sprague-Dawley rats were randomly divided into five groups (n=5 per group): model group, agomir NC group, agomir group, ligustrazine+agomir NC group, and ligustrazine+agomir group. The rats in the agomir group and ligustrazine+agomir group were intraarticularly injected with miR-20b-5p agomir solution, while the rats in the agomir NC group and ligustrazine+agomir NC group were intraarticularly injected with the same dose of miR-20b-5p agomir NC solution. The model group was injected with the same amount of normal saline intraarticularly and intragastrically. The rats in the ligustrazine+agomir group and ligustrazine+agomir NC group were also given intragastric administration of ligustrazine. Intraarticular administration was done only once and intragastric administration was performed once a day for 4 weeks. Four weeks later, the rats in each group were killed and the left knee joint was fixed and made into paraffin sections for hematoxylin-eosin staining, Safranin O-fast green staining, and immunohistochemical staining. RESULTS AND CONCLUSION: In synovial tissue, the vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). The vascular density, inflammatory cell infiltration, vascular endothelial growth factor protein and Notch1 protein in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). In cartilage and subchondral bone tissues, the loss of cartilage matrix and vascular invasion in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were slighter than those in the model group and agomir NC group. In cartilage and subchondral bone tissues, Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein in the agomir group, ligustrazine+agomir NC group and ligustrazine+agomir group were significantly lower than those in the model group and agomir NC group (P < 0.05). Osteoarthritis Research Society International score, vascular endothelial growth factor protein and Notch1 protein expression in the ligustrazine+agomir group were significantly lower than those in the agomir group and ligustrazine+agomir NC group (P < 0.05). To conclude, ligustrazine and overexpression of miR-20b-5p in synovium, cartilage and subchondral bone may inhibit vascular endothelial growth factor/Notch1 mediated angiogenesis, improve various histological manifestations to some extent, and alleviate disease progression in rats with earlystage knee osteoarthritis. [ABSTRACT FROM AUTHOR]

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