抗抑郁剂对去卵巢抑郁模型大鼠骨质疏松相关蛋白的影响

Effects of antidepressants on osteoporosis related protein OPG, RANKL and RANK in ovariectomized rat model with depressive disorder

目的观察抗抑郁剂对去卵巢抑郁模型大鼠骨质疏松相关蛋白OPG、RANKL、RANK的影响。方法40只成年雌性大鼠分为假手术＋生理盐水组（sn）、抑郁模型＋生理盐水组（Dn）、去卵巢＋生理盐水组（On）、去卵巢＋抑郁模型＋生理盐水组（ODn）、去卵巢＋抑郁模型＋舍曲林组（ODs）、去卵巢＋抑郁模型＋西酞普兰组（ODx）、去卵巢＋抑郁模型＋瑞波西汀组（ODr）、去卵巢＋抑郁模型＋文拉法辛组（ODw）。双侧卵巢切除建立去卵巢大鼠模型。对抑郁模型组、去卵巢＋抑郁模型组运用慢性轻度不可预知性刺激结合孤养制备抑郁模型，于实验前1d和第28天运用敞箱实验和糖水消耗实验评定大鼠行为学改变。用免疫组化、实时荧光定量PCR检测大鼠股骨颈OPG、RANKL和RANK的改变。结果Dn组在应激后水平运动得分、垂直运动得分及糖水消耗百分比较Sn组显著降低（P〈0．05），ODn组也比On组显著下降（P〈0．05）；与Sn组比较，Dn组和On组的RANK蛋白及其mRNA均升高（均P〈0．05），与Sn组比较，Dn组和On组的RANKL及mRNA水平均升高（均P〈0．05），ODs（5．94±0．79）、ODw（5．99±1．08）、ODr（6．59±0．69）较ODn（4．96±0．51）组OPG基因表达降低（均P〈0．05）；ODs（2．82±0．23）、ODx（3．03±0．04）较ODn（3．44±0．18）组RANK基因表达增高（均P〈0．05）；ODs（4．82±0．94）、ODx（5．00±0．82）、ODw（5．23±0．88）较ODn（3．69±0．69）RANKL基因表达降低（均P〈0．05）。结论抑郁模型与去卵巢模型大鼠股骨颈RANK、RANKL的表达升高；抗抑郁剂对去卵巢抑郁模型大鼠股骨颈RANK的基因表达有一定上调作用，对OPG、RANKL的基因表达有一定下调作用，且以舍曲林作用最强，瑞波西汀作用最弱。

Objective To investigate the effects of antidepressant therapy on whole regulating function of OPG/RANKL/RANK system in ovariectomized （OVX） rat model with depressive disorder. Methods Forty sexually mature female SD rats were used as subjects. The rats were randomly divided into 8 groups as following： sham group（ Sn）, depression group（ Dn）, the OVX group （On）, the OVX with depression group（ ODn）, OVX with depression ＋sertraline group （ODs）, and OVX with depression ＋ citalopram （ODx）, OVX with depression ＋ reboxetine group（ ODr）, OVX with depression ＋ venlafaxine group （ODw）. Bilateral oophorectomy was applied to establish the ovariectomized rats model. Chronic unpredictable mild stress（CUMS） was used to estalish depression model. Open-field test and sugar consumption experiment were applied before the experiment and the 28th day of the experiment. Immunohistochemistry and Quantita- tive Real-time PCR were used to observe the expression of OPG, RANKL and RANK. Results After chronic unpredictable mild stress the scores of horizontal motion, vertical motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the in control Sn group （P〈 0. 05 ） and the scores in ODn group were decreased in contrast to the On group （P〈0.05）.The protein and gene expression of RANK in Dn group and On group were increased in contrast to the Sn group （P〈0.05）. The protein and gene expression of RANKL in Dn group and On group were increased in contrast to the Sn group （P〈0.05）.The gene expression of OPG in ODs group（5.94±0.79） ,ODw group（5.99±1.08） and ODr group（6,59±0,69）was decreased in contrast to the ODn group（4.96±0.51 ）（P〈0.05）.The gene expression of RANK in ODs group（ 2.82±0.23）, ODx group（3.03±0.04） was increased in contrast to the ODn group（3,44±0.18） （P〈0.05）, The gene expression of RANKL in ODs group（4.82±0.94）,ODx greup（5.00±0.82） and ODw group（5.23±0.88） was decreased in contrast to the ODn group（3.69±0,69） （P〈0,05）. Conclusion The expression of RANK and RANKL in femoral neck is increased both in depressive disorder model rats and ovariectomized model rats, The antidepressant can up-regulate the expression of RANK, and down-regulate the expression of OPG and RANKL in the OVX with depression group, Of the effect, sertraline is the strongest, however reboxetine mesylate is the poorest.