虫草素通过调节COX-2/PGE2信号通路促进骨质疏松大鼠的骨折愈合

Cordycepin promotes fracture healing in osteoporosis rats by regulating COX-2/PGE2 signal pathway

目的探讨虫草素(Cordycepin)调控环氧化酶2(COX-2)/前列腺素E2(PGE2)信号通路对骨质疏松大鼠骨折愈合的影响。方法制备骨质疏松大鼠模型,将大鼠分为Sham组、Model组、Cordycepin组(10 mg/kg腹腔注射)、Cordycepin+NS-398组(腹腔注射10 mg/kg的Cordycepin+10 mg/kg的COX-2抑制剂),分别检测骨折愈合情况、骨密度(BMD)及生物力学性能,HE染色观察骨痂组织病理学变化,ELISA法检测血清ALP、CTX-Ⅰ、OC水平及骨痂组织COX-2、PGE2、cAMP水平,免疫组化法检测骨痂组织COX-2、VEGF表达。结果与Sham组比较,Model组骨折线明显,X光片评分、BMD、骨最大负荷与刚度、ALP、OC水平显著降低、骨组织COX-2、PGE2、cAMP、VEGF表达水平显著降低,CTX-Ⅰ水平显著升高(P<0.05);与Model组比较,Cordycepin组X光片评分、BMD、骨最大负荷与刚度、ALP、OC水平显著升高、骨组织COX-2、PGE2、cAMP、VEGF表达水平显著升高,CTX-Ⅰ水平显著降低(P<0.05);NS-398可逆转Cordycepin对骨质疏松大鼠骨折愈合的促进作用。结论虫草素可能通过激活COX-2/PGE2信号通路,促进骨质疏松大鼠的骨折愈合。

Objective To investigate the effects of cordycepin on fracture healing by regulating cyclooxygenase-2(COX-2)/prostaglandin E2(PGE2)signal pathway in rats with osteoporosis.Methods Rat osteoporosis model was prepared.The rats were grouped into Sham group,Model group,Cordycepin group(10 mg/kg intraperitoneal injection),and Cordycepin+NS-398 group(10 mg/kg Cordycepin+10 mg/kg COX-2 inhibitor intraperitoneal injection).The fracture healing,bone mineral density(BMD),and biomechanical properties were measured respectively.HE staining was used to observe the histopathological changes of the callus.Serum levels of ALP,CTX-Ⅰ,OC,and the levels of COX-2,PGE2 and cAMP in the callus tissue were detected with ELISA.The expressions of COX-2 and VEGF in the callus were detected with immunohistochemistry.Results Compared with those in Sham group,the fracture line of Model group was obvious,X-ray score,BMD,maximum load,and stiffness of callus,and the levels of ALP and OC reduced obviously,the expression levels of COX-2,PGE2,cAMP and VEGF in bone tissue decreased obviously,and the level of CTX-Ⅰincreased obviously(P<0.05).Compared with those in the model group,the X-ray score,BMD,maximum load and stiffness of the bone,the levels of ALP and osteocalcin in the Cordycepin group increased obviously,the expression levels of COX-2,PGE2,cAMP,and VEGF in the bone tissue increasedobviously,and the level of CTX-Ⅰreduced obviously(P<0.05).NS-398 reversed the promoting effect of Cordycepin on fracture healing in osteoporosis rats.Conclusion Cordycepin promotes fracture healing in osteoporosis rats by activating COX-2/PGE2 signal pathway.