雌激素对去卵巢大鼠骨组织Wnt16、 β-catenin 、 OPG 、RANKL表达的影响

摘要

目的 研究雌激素对去卵巢大鼠骨组织中Wnt 16、β-catenin、OPG、RANKL表达的影响,探讨雌激素对骨组织的保护作用.方法 选取3月龄Wistar雌性大鼠40只,随机分为假手术组、去势组、实验组1和实验组2.两组实验组分别给予17β-雌二醇皮下注射4周和16周,其余两组给予等量0.9％氯化钠溶液.16周后测定骨组织中Wnt 16、OPG、RANKL、β-catenin表达量,HE染色分析大鼠胫骨平台处骨小梁厚度(Tb.Th)、骨小梁数目(Tb.N)和骨小梁间距(Tb.SP)变化,ELISA法测定血清雌二醇(E2)水平.结果 假手术组、实验组2与去势组比较,OPG、β-catenin、Wnt16 mRNA、血清E2水平、Tb.Th和Tb.N明显升高,RANKL水平和Tb.SP明显下降,差异均有统计学意义(均P＜0.05).实验组1与去势组相比,β-catenin、血清E2水平、Tb.Th和Tb.N明显升高,RANKL水平和Tb.SP明显下降,差异均有统计学意义(均P＜0.05).结论 雌激素可能通过上调Wnt16、β-catenin、OPG表达,下调RANKL表达,来预防骨质疏松.%Objective To investigate the effects of estrogen on the expression of Wnt16,β-catenin,OPG,RANKL in bone tissue of ovariectomized rats.Methods Forty female Wistar rats were randomly divided into sham operation group,ovariectomized group,estrogen group 1 and estrogen group 2.In the estrogen groups,17 β-E2 was injected subcutaneously for 4 weeks or 16 weeks after ovariectomy,respectively.The other two groups were given the same volume of normal saline.The expression of Wnt16 mRNA was detected with RT-PCR,the expressions of OPG,RANKL,β-catenin proteins in bone cortex tissue were detected with Western blot and immunohistochemistry,respectively.The thickness of the trabecular bone (Tb.Th),number of trabecular bone (Tb.N) and thetrabecular spacing (Tb.SP) were measured using HE staining analysis,and serum E2 level was determined by ELISA.Results Compared to ovariectomized group,The expression of OPG,β-catenin,Wnt16 mRNA in bone tissue,the serum E2 levels,and Tb.Th,Tb.N in estrogen group 2 and sham operation group were significantly increased,the expression of RANKL and Tb.SP were significantly decreased(all P＜0.05).Compared to ovariectomized group the expression of β-catenin,serum E2,and Tb.Th,Tb.N in estrogen group 1 were significantly increased,the expression of RANKL and Tb.SP were significantly decreased (all P＜0.05).Conclusion Estrogen may prevent osteoporosis by up-regulation of Wnt16,β-catenin,OPG and down-regulation RANKL expression in bone tissue.