目的激素性股骨头缺血性坏死(osteonecrosis of the femoral head,ONFH)防治效果不理想,探讨六味地黄丸预防ONFH的可行性及分子机制,为预防激素性ONFH提供实验依据。方法取成年健康昆明小鼠36只,体重40～50g,平均46g,随机分为3组(n=12):空白对照组(A组)、马血清/激素组(B组)、马血清/激素/六味地黄丸组(C组)。B、C组均2次腹腔注射马血清,2次剂量分别为10mL/kg及5mL/kg,间隔2周;第2次注射马血清同时肌肉注射醋酸泼尼松龙45mL/(kg·d),共5d,制备激素性ONFH小鼠模型。于应用激素同时B组灌服生理盐水10mL/(kg·d),C组灌服六味地黄丸2g/(kg·d);A组同时间点肌肉注射及灌服等量生理盐水。观察小鼠一般情况,于第1次激素注射后2、4、8周处死小鼠,大体观察股骨头情况,取双侧股骨头及肝脏行组织学及免疫组织化学染色观察,TUNEL法检测细胞凋亡情况。结果B、C组分别于第2次腹腔注射马血清后死亡2只及1只小鼠,余小鼠均存活至实验完成。3组各时间点股骨头外观、形态及关节软骨面均正常。组织学观察示A组各时间点肝脏及股骨头均正常。B组第1次激素注射后2周肝细胞肿胀,细胞内可见小脂肪空泡,肝索结构不清,肝窦变窄;股骨头区骨小梁纤细、稀疏,部分可见断裂;且随时间推移,变化愈显著。C组各时间点肝脏及股骨头与A组相似。B组股骨头空骨陷窝率高于A、C组(P<0.01),A、C组间比较差异无统计学意义(P>0.05)。免疫组织化学染色观察,各时间点B组与A、C组比较,股骨头骨保护素局部表达阳性率下降,骨保护素配体局部表达阳性率上升,差异均有统计学意义(P<0.01)。细胞凋亡检测示B组较A、C组骨细胞凋亡指数显著升高,差异有统计学意义(P<0.01),A、C组间2、4周比较差异有统计学意义(P<0.05),8周差异无统计学意义(P>0.05)。结论六味地黄丸具有改善骨代谢、保护骨细胞、降脂等作用,可通过抑制小鼠股�
Objective To investigate the relations between neuroapoptosis and the onset and development of Alzheimer’s disease （AD）, especially the role of NF-κB in the regulation of neuroapoptosis. Methods Caspase-3 and NF-κB （p50） expressions in the CA3 region of the hippocampus in APPswe Tg2576 transgenic mice were studied from postnatal day 0-180, using Nissl staining, immunohistochemistry and RT-PCR methods. Results Both neuronal apoptosis and NF-κB activity decreased gradually with the increase of age in wild type and Tg2576 mice. However, the number of caspase-3-positive or NF- κB-positive pyramidal cells in Tg2576 mice was greater than that in age-matched wild type mice, with significant differences after postnatal day 14 （P 0.01 or P 0.05）. Linear regression analyses of caspase-3 and NF-κB expression demonstrated a correlation between neuroapoptosis and activity of NF-κB. Conclusion The process of neuroapoptosis is consistent with the onset and development of AD. Furthermore, the observed correlation between neuroapoptosis and NF-κB activity suggests a role of NF-κB in hippocampal neuroapoptosis.
