Effect of alcohol extract from Agkistrodon acutus on rat pain model of osteoarthritis and its mechanism
Objective To explore the efficacy and possible mechanism of Agkistrodon acutus alcohol extract on osteoarthritis(OA).Methods Thirty SD rats were randomly divided into control group,model group and Acutokus acutus alcohol extract group(extract group),with ten rats in each group.The OA pain model was established by the joint injection of iodoacetic acid(MIA).Seven days after modeling,the rats in extract group were injected with 0.2 mL Agkistrodon acutus alcohol extract(0.6 g/kg),and the rats in control and model groups were injected with the same amount of saline,once a week for continuous 4 weeks.Mechanical and thermal pain thresholds were measured before and 4 weeks after administration.Pain behavior evaluation,histopathological observation,immunohistochemical analysis,terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling(Tunel)staining and Western blot were used to evaluate the in vivo efficacy of Agkistrodon acutus alcohol extract on OA rats and explore its potential mechanism of action.Results The model of OA pain rats was established successfully.Compared with the control group,the joint tissues of model group showed the pathological state of cartilage degeneration,reduced number of chondrocytes,massive destruction of collagen and matrix disorder.Compared with the model group,the pathological state of the rats in extract group was improved and the pain thresholds of mechanical pain and thermal pain increased significantly(P＜0.01),while the Osteoarthritis Research Society International(OARSI)scores were significantly lower than those of the model group(P＜0.01).Immunohistochemical results showed that in extract group,the positive expression rate of collagen type Ⅱ(Col2)in rat joints increased while that of matrix metalloproteinase 13(MMP-13)decreased;Tunel test results showed that cell apoptosis rate was significantly reduced(P＜0.01).Based on Western blot,the protein expression levels of MMP-13,poly ADP-ribose polymerase(PARP)and phosphorylated p65(p-p65)in extract group were significantly decreased(all P＜0.05).Conclusion Agkistrodon acutus alcohol extract inhibits cell apoptosis by regulating PARP/NF-κB pathway,promotes the balance of cartilage metabolism,relieves joint pain and repairs cartilage damage.
Agkistrodon acutus extractOsteoarthritisMechanism of action
万方数据
维普
