骨质疏松发生一氧化氮机制及雌激素调控作用研究

Effects of nitric oxide on osteoporosis and regulation and control of estrogen

目的 研究骨质疏松发生的一氧化氮机制及雌激素防治骨质疏松作用的一氧化氮通路 ,深入理解骨质疏松症病理过程中一氧化氮作用环节。方法 45只SD雌性大鼠分为①假手术组(Sham组 ) ;②卵巢切除组 (OVX组 ) ;③OVX +倍美力治疗 (Premarin组 )。进行iNOS原位杂交及iNOS、eNOS免疫组化研究 ,测定其平均灰度值及平均积分光密度 (ODI)作统计指标。结果 iNOS原位杂交实验结果显示 :正常大鼠去卵巢后 ,骨髓腔内及骨小梁表面iNOSmRNA有强阳性表达 ,差异有非常显著性 (P <0 0 1) ,iNOS免疫组化实验结果也显示OVX组iNOS阳性表达明显较Sham组增加 ;而Pre marin组iNOS表达强度较OVX组明显降低 (P <0 0 5 )。OVX组与Sham组eNOS表达差异无显著性 ,Premarin组较OVX组eNOS表达强度则明显增加 (P <0 0 5 )。结论 NO是调节OB、OC功能活动的一种重要效应因子 ,NO导致细胞因子诱导性骨吸收增强与绝经后雌激素缺乏OP密切相关。雌激素可下调iNOSmRNA表达 ,抑制iNOS蛋白合成 ,从而减轻功能亢进的OC性骨吸收 ,而对骨组织正常生理活动中的eNOS合成 ,有适度促进作用 ,有利于骨组织的重建及骨量的恢复 ,从而重建骨形成

Objective To explore the effect of nitric oxide on osteoporosis and the relationship between estrogen treatment and nitric oxide Methods Forty five SD rats, 10 month old, were sham operated (Sham)or surgically ovariectomized (OVX) or OVX+ estrogen (Premarin) treated The rats were sacrificed at 12 weeks post surgery In situ hybridization was used to detect the expression of iNOS mRNA,immunnohistochemistry was used to study the expression of iNOS or eNOS,and image analysis was done to measure the gray scale and average integral optical density (ODI) Results In the OVX group,the expression of iNOS mRNA and the synthesis of iNOS significantly increased,compared to that in Sham group ( P <0 01)?In the premarin group,the expression of iNOS was significantly decreased There was no significant difference in the expression of eNOS between OVX group and Sham group, but the expression of eNOS significantly increased in the Premarin group ( P <0 05) Conclusion Nitric oxide (NO) induction by nitric oxide synthase (NOS) is not only a physiological mediator,but also a pathologic factor;it plays an important role in the process of osteoporosis Decreased expression of estrogen and increased expression of proinflammatory cytokines will stimulate bone resorption by induction of NOS to generate NO Estrogen can protect the osteoporotic rats from bone loss by NOS ways, facilitating the coupling of bone formation and resorption