雷诺昔酚对去势后大鼠松质骨中TNF-α表达及骨密度的影响

Influence of raloxifene on expression of TNF-α in cancellous bone and bone mineral density in ovariectomized rats

目的选择性雌激素受体调节剂(SERM)—雷诺昔酚(RAL)对去卵巢大鼠骨密度及松质骨中TNF-α表达的影响.方法将8月龄未经产雌性二级SD大鼠30只,随机分为假手术(SHAM)组、去势(OVX)组、去势+雷诺昔酚(OVX+RAL)组.OVX+RAL组大鼠术后第2日开始给予雷诺昔酚灌胃.术后20wk处死各组大鼠,对各组大鼠不同部位骨密度(BMD)进行检测.利用免疫组织化学染色及用图像分析方法对各组大鼠松质骨切片TNF-α表达图像进行分析,观察RAL对OVX大鼠腰椎松质骨中TNF-α表达的影响.结果①DVX组与SHAM组相比较,TNF-α表达的灰度值降低(P<0.01);RAL组较OVX组灰度值升高(P<0.01),表明OVX大鼠松质骨中骨小梁周围及髓腔内TNF-α表达阳性细胞数多于SHAM组;而经RAL治疗后的去卵巢大鼠骨小梁周围及髓腔内TNF-α阳性表达减弱.②与SHAM组相比,OVX组股骨近端、股骨干、腰椎BMD降低(P<0.01);RAL治疗组各部位BMD高于OVX组(P<0.05),接近SHAM组水平(P>0.05).结论RAL可通过抑制破骨性因子TNF-α表达来抑制因雌激素缺乏引起的骨密度降低及骨形态结构退变.

AIM： To discuss the influence of selective estrogen receptor modulator（SERM） raloxifene（RAL） on the expression of TNF-α in cancellous bone and bone mineral density （BMD） loss in ovariectomized rats. METHODS： Thirty 8-month nulliparous female SD rats were divided into 3 groups （ 10 rats per group ） ： sham operation （ SHAM ） group, ovariectomized （OVX） group and therapeutic （OVX ＋ RAL）group. Bilateral ovariectomies were done on OVX group and OVX ＋ RAL group. Sham operation was performed on SHAM group. OVX ＋ RAL group was treated with RAL 2 d after operation. Twenty weeks after operation, all rats were sacrificed. BMD of L3-L5 vertebrae, proximal femoral segment, femoral body were measured by dual energy X-ray absorptiometry（DEXA）. SABC immunohistochemistry and image analysis were used to detect the expression of TNF-α in L2 vertebral bone of every group. RESULTS ： ① The gray scale of TNF-α in cancellous bone in OVX group was lower than that in SHAM group （P〈0.01）, and also lower than that in OVX ＋ RAL group （P 〈0.01 ）, indicating that the expression of TNF-α in cancellous bone in OVX group increased after ovariectomy, and became weak after RAL treatment. ② Twenty weeks after ovarieetomy, BMD of L3 -L5 vertebrae, proximal femoral segment, femoral body of ovariectomized rats decreased significantly and the trabecular bone became thinner and irregular as compared with SHAM group （ P 〈 0.01 ）. After treatment of RAL, the above parameters were maintained close to the level of SHAM group （P 〉 0. 05 ）. CONCLUSION： RAL could inhibit the expression of TNF-α in cancellous bone of ovariectomized rats and depress the occurrence of osteoporosis in ovariectomized rats.