Nrf2/HO-1信号通路在电针治疗膝骨关节炎大鼠中的作用OA

Objective:To investigate the role of the Nrf2/HO-1 signaling pathway in electroacupuncture(EA)treatment for rats with knee osteoarthritis.Methods:Sixteen 24-month-old Sprague-Dawley(SD)male rats were randomly divided into the elderly group and the EA group(n=8 each).Eight 6-month-old SD male rats were selected as the young group.The EA group received electroacupuncture at bilateral Taixi,Zusanli,Yanglingquan,and Xuehai.EA parameters:dense-disperse wave(3 Hz sparse wave,15 Hz dense wave),1 mA current intensity,30 minutes per session,once daily,5 days per week for 8 weeks.The remaining two groups did not receive EA intervention.Serum CTX-II level was detected by ELISA.Micro-CT was used to detect the microstructure of the left tibial subchondral bone.Safranin O-fast green staining was used to evaluate cartilage morphology of the left tibial plateau,with joint cartilage degeneration assessed using the modified Mankin's score.RT-PCR and Western blotting detected mRNA and protein expression levels of aggrecanase-1,aggrecanase-2,Nrf2,and HO-1 in cartilage tissue of the right tibial plateau.Results:(1)Compared with the young group,the serum CTX-II level in the elderly group was increased(P<0.05).Micro-CT showed that the bone mineral density(BMD),bone volume fraction,and trabecular number in the elderly group were all reduced(P<0.05),and the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that the cartilage surface structure in the elderly group was incomplete with fissures,the boundary between cartilage and subchondral bone was unclear,chondrocyte morphology and structure were abnormal,there was severe calcification,decreased cell count,and uneven staining in the articular cartilage,and the Mankin's score was increased(P<0.05).The mRNA and protein expression levels of aggrecanase-1 and aggrecanase-2 were increased(P<0.05),while the mRNA and protein expression levels of Nrf2 and HO-1 were reduced(P<0.05).(2)Compared with the elderly group,the serum CTX-II level in the EA group was reduced(P<0.05).Micro-CT showed that the bone mineral density(BMD),bone volume fraction,and trabecular number in the EA group were all increased(P<0.05),and the trabecular separation was decreased(P<0.05).Safranin O-fast green staining showed that the cartilage surface was slightly flattened,with fewer fissures,increased chondrocyte count,more uniform staining,and chondrocyte morphology between that of the young group and the elderly group.The Mankin's score was decreased(P<0.05).The mRNA and protein expression levels of aggrecanase-1 and aggrecanase-2 were decreased(P<0.05).The mRNA expression levels of Nrf2 and HO-1 and the protein expression level of Nrf2 were increased(P<0.05),while the protein expression level of HO-1 tended to increase(P>0.05).Conclusion:Electroacupuncture may alleviate articular cartilage degradation,improve subchondral bone microstructure,and protect cartilage by activating the Nrf2/HO-1 signaling pathway.