P53/P21通路在电针抑制骨质疏松大鼠模型成骨细胞衰老中的机制

Study on the mechanism of P53/P21 pathway in electroacupuncture inhibiting osteoblast aging in osteoporotic rats

目的探讨电针对老年大鼠骨质疏松及衰老细胞通路P53/P21的影响。方法27月龄雄性大鼠随机分为老年组和电针治疗组(n=8),电针治疗组接受电针干预(每周5次,共8周),6月龄雄性大鼠设为青年组。8周后处死大鼠,ELISA检测血清Ⅰ型胶原C末端肽(CTX-I)、Ⅰ型胶原羧基端前肽(PICP)水平;Micro-CT扫描骨组织;检测P53、P21等mRNA及蛋白表达水平。结果老年组CTX-I较青年组增加,PICP较青年组降低(P<0.01);电针可降低老年大鼠CTX-I,增高PICP(P<0.01);Micro-CT显示相对青年组,老年组大鼠骨小梁分布紊乱、稀疏,BMD、BV/TV、Tb.N等下降(P<0.01),Tb.Sp增高(P<0.01)。电针可改善骨小梁紊乱分布,增加BMD、BV/TV、Tb.N(P<0.05),降低Tb.Sp(P<0.01)。相对于青年组,老年组大鼠P53、P21 mRNA及蛋白表达量增高(P<0.01)。电针能下调老年大鼠P53、P21 mRNA及蛋白表达量(P<0.01)。结论电针可能通过抑制P53/P21信号通路来缓解成骨细胞衰老、增加成骨细胞活性,并以此来促进骨形成,改善骨质疏松。

Objective The research aimed to explore the effects of Electroacupuncture on osteoporosis and P53/P21 signal pathway in elderly rats.Methods Twenty-seven-month-old male SD rats were randomly divided into two groups:elderly group(n=8),electroacupuncture treatment group(n=8).Six-month-old male SD rats were young group(n=8).The treatment group was treated with electroacupuncture intervention five times a week for a total of 8 weeks.All rats in each group were sacrificed at 8 weeks.The serum bone metabolism indexes(CTX-I,PICP)were detected by using ELISA system;Micro-CT scanner were performed to evaluate the microstructure of bone tissue;The expression levels of P53/P21 m RNA and protein were detected by RT-PCR and Western blot.Results The levels of serum CTX-I in elderly group were higher than the young group(P<0.01),while PICP was lower than that in the young group(P<0.01).Electroacupuncture caused decrease in CTX-I and increase in PICP compared to the elderly group(P<0.01).The BMD,BV/TV,Tb.N of bone tissue in elderly group were significantly lower contrast with young group(P<0.01),while the Tb.Sp in elderly group was significantly higher compared with young group(P<0.01).Compared with the elderly group,Electroacupuncture caused increase in BMD,BV/TV,Tb.N(P<0.05)and decrease in Tb.Sp(P<0.01).The expressions of P53/P21 m RNA and protein in the elderly group were significantly higher than the young group(P<0.01).Compared with the elderly group,the expressions of P53/P21 mRNA and protein in the electroacupuncture treatment group were significantly reduced(P<0.01).Conclusion Electroacupuncture can effectively improve osteoporosis in elderly rats.The mechanisms may be to alleviate osteoblast aging and increase osteoblast activity by inhibiting P53/P21 signal pathway,so as to promote bone formation and reduce bone loss.