基于COX2-PGE2-cAMP通路探讨田七元胡胶囊对胫骨骨折大鼠的镇痛作用机制OA

Objective To explore the role of Tianqi Yuanhu capsule in fracture pain management and its regulatory mechanism on COX2-PGE2-cAMP signaling pathway,and to provide a scientific basis for the analgesic effect of this proprietary Chinese medicine preparation in clinical application.Methods The tibial fracture model of SD rats was used,and 24 rats were randomly divided into the sham-operation group,the model group,the Tianqi Yuanhu group and the celecoxib group,with 6 rats in each group.The sham-operation group and model group were gavaged with 0.9%saline,while the Tianqi Yuanhu group and celecoxib group were gavaged with 108 mg/kg of Tianqi Yuanhu and 0.2 g/kg of celecoxib,respectively.The serum levels of prostaglandin E2(PGE2)and cyclic adenosine monophosphate(cAMP)were measured by enzyme-linked immunosorbent assay(ELISA)on the first and seventh postoperative days,and the protein expression of cyclooxygenase(COX)-1 and COX2 was detected by protein blotting(WB)in the peripheral tissues of the tibial parietal.Results On the first postoperative day,the serum PGE2 and cAMP levels in the model group,Tianqi yuanhu group,and celecoxib group were higher than those in the sham-operated group,and the differences were statistically significant(P<0.05);there was no statistically significant difference in the comparison of serum PGE2 and cAMP levels between the model group and the Tianqi yuanhu group,between the Tianqi yuanhu group and the celecoxib group,and between the model group and the celecoxib group(P>0.05).On the seventh postoperative day,the levels of PGE2 and cAMP were lower in the Tianqi yuanhu group and the celecoxib group than in the model group,and the difference was statistically significant(P<0.05);the comparison of the levels of PGE2 and cAMP between the Tianqi yuanhu group and the celecoxib group showed no statistically significant differences(P>0.05).The results of the WB showed that,compared with the first day,in the tissues surrounding the fracture in the Tianqi Yuanhu group on the seventh day,the expression of COX1 and COX2 was significantly down-regulated,and the difference was statistically significant(P<0.05);on the seventh day after surgery,the expression levels of COX1 and COX2 in the parietal tissues of the tibia in the Tianqi Yuanhu group were lower than those in the model group,and the difference was statistically significant(P<0.05).Conclusion Tianqi Yuanhu Capsule alleviates post-fracture pain by regulating the COX2-PGE2-cAMP pathway,reducing PGE2,cAMP,and COX1/COX2 levels.These findings support its clinical potential.