补肾壮骨颗粒对去势雌性大鼠骨组织雌激素受体蛋白表达的影响
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摘要
目的探讨补肾壮骨颗粒对去势雌性大鼠骨组织雌激素受体α(ERα)、雌激素受体β(ERβ蛋白表达的影响。方法将60只6月龄SPF级SD雌性大鼠随机均分为模型组(OVX组)、假手术组(SHAM组)、中药组(CM组)、戊酸雌二醇组(EV组)、雷洛昔芬组(RLX组)。各组给药3个月后,每组随机选取半数大鼠测定其脊柱及股骨颈骨密度(BMD),腹主动脉采血处死,立即保留血清并取其左侧股骨,进行血清雌二醇(E2)含量及骨组织ERα及ERβ蛋白表达水平的检测,给药6个月后采用相同方法处理剩余大鼠。结果与SHAM组比较,各阶段用药后,OVX组脊柱及股骨颈BMD值均下降(P <0.05,P <0.001)。与OVX组相比,用药3个月后CM组脊柱及股骨颈BMD值均提高,差异有统计学意义(P <0.01,P <0.05);6个月后各用药组脊柱BMD值均升高(P <0.05),股骨颈BMD值亦提高,其中CM组提高较明显,差异有统计学意义(P <0.05)。与SHAM组相比,两阶段给药后OVX组ERα、ERβ水平均显著降低(P <0.001),与OVX组比较,各用药组两种蛋白水平均显著提高(P <0.001)。用药3个月后,3个用药组之间比较差异无统计学意义(P> 0.05);6个月后,CM组ERα蛋白水平高于RLX组(P <0.05),与EV组比较差异无统计学意义(P> 0.05)。给药3、6个月后,CM组E2含量较OVX组均有提高(P <0.05)。结论补肾壮骨颗粒对去卵巢雌鼠骨组织可能具有类雌激素样作用,且可在一定程度上提高ERα、ERβ蛋白表达水平,提高去卵巢大鼠BMD。
Objective To investigate the effects of Bushen Zhuanggu granules on the expression of estrogen receptor alpha(ERα)and estrogen receptorβ(ERβ)protein in bone tissue of ovariectomized rats.MethodsSixty female SPF-class SD female rats aged six months were randomly divided into ovarian group(OVX),sham operation group(SHAM),Chinese medicine group(CM),estradiol valerate group(EV),and raloxifene group(RLX).After 3 months of administration in each group,half of the rats in each group were randomly selected to measure the bone mineral density(BMD)of spine and femur.Then the rat abdominal aorta was sacrificed with the serum removed and the left femur was taken immediately for the detection of serumand the expression of ERαand ERβprotein in each group.The remaining rats were treated in the same manner after 6 months.administration.Results Compared with those in the SHAM group,the BMD of the spine and femur in the OVX group decreased(P<0.05,P<0.001)after each stage of medication.Compared with those in the OVX group,the BMD of the spine and femoral neck of the CM group were both increased(P<0.01,P<0.05)after 3 months.The spinal BMD of each group was increased(P<0.05),meanwhile that of the CM group was much higher than that of the other two groups and the difference was statistically significant(P<0.05).Compared with those in the SHAM group,the levels of ERαand ERβin the OVX group were significantly lower after two-stage of administration(P<0.001).Compared with those in the OVX group,the levels of the two proteins in all drug groups were significantly increased(P<0.001).After 3 months of treatment,there was no significant difference among the three drug groups(P>0.05).And 3 months later,the level of ERαprotein in CM group was higher than that in RLX group(P<0.05),but there was no difference when compared with EV group(P>0.05).The serumin the CM group was higher than that in the OVX group(P<0.05)after 3 and 6 months.Conclusions Bushen Zhuanggu Granules may have an estrogen-like effect on the bone tissue of ovariectomized rats,and can increase the expression levels of ERαand ERβproteins to a certain extent and increase the BMD of ovariectomized rats.
Objective To investigate the effects of Bushen Zhuanggu granules on the expression of estrogen receptor alpha(ERα)and estrogen receptorβ(ERβ)protein in bone tissue of ovariectomized rats.MethodsSixty female SPF-class SD female rats aged six months were randomly divided into ovarian group(OVX),sham operation group(SHAM),Chinese medicine group(CM),estradiol valerate group(EV),and raloxifene group(RLX).After 3 months of administration in each group,half of the rats in each group were randomly selected to measure the bone mineral density(BMD)of spine and femur.Then the rat abdominal aorta was sacrificed with the serum removed and the left femur was taken immediately for the detection of serumand the expression of ERαand ERβprotein in each group.The remaining rats were treated in the same manner after 6 months.administration.Results Compared with those in the SHAM group,the BMD of the spine and femur in the OVX group decreased(P<0.05,P<0.001)after each stage of medication.Compared with those in the OVX group,the BMD of the spine and femoral neck of the CM group were both increased(P<0.01,P<0.05)after 3 months.The spinal BMD of each group was increased(P<0.05),meanwhile that of the CM group was much higher than that of the other two groups and the difference was statistically significant(P<0.05).Compared with those in the SHAM group,the levels of ERαand ERβin the OVX group were significantly lower after two-stage of administration(P<0.001).Compared with those in the OVX group,the levels of the two proteins in all drug groups were significantly increased(P<0.001).After 3 months of treatment,there was no significant difference among the three drug groups(P>0.05).And 3 months later,the level of ERαprotein in CM group was higher than that in RLX group(P<0.05),but there was no difference when compared with EV group(P>0.05).The serumin the CM group was higher than that in the OVX group(P<0.05)after 3 and 6 months.Conclusions Bushen Zhuanggu Granules may have an estrogen-like effect on the bone tissue of ovariectomized rats,and can increase the expression levels of ERαand ERβproteins to a certain extent and increase the BMD of ovariectomized rats.
引文
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[11]彭珊,欧阳厚淦,赵志冬,等.去卵巢大鼠骨质疏松模型的制备与评价[J].中国骨质疏松杂志,2017,23(10):1327-1329.
[12]KHARODE Y P,SHARP M C,BODINE P V N.Utility of the ovariectomized rat as a model for human osteoporosis in drug discovery[M]//Osteoporosis.New Jersey:Humana Press,2008:111-124.
[13]汤璐璐,邓伟民,苏海容,等.补肾壮骨颗粒对SAMP6小鼠股骨宏观结构及生物力学的影响[J].中国骨质疏松杂志,2018,24(1):91-97.
[14]苏海容,汤璐璐,袁人飞,等.补肾壮骨颗粒通过GH/IGF-1轴影响快速老化小鼠骨密度[J].实用医学杂志,2017,33(15):2459-2464.
[15]JIANG H,BAI W,WANG W,et al.Proteomics in plasma of ovariectomized rats and those exposed to estradiol valerate[J].JSteroid Biochem Mol Biol,2017,178:1-12.
[16]LI T,MA Y,ZHANG H,et al.Differential regulation of morphology and estrogen receptor-alpha expression in the vagina of ovariectomized adult virgin rats by estrogen replacement:a histological study[J].Int J Endocrinol,2016,2016(1):1-8.
[2]LANYON L,ARMSTRONG V,ONG D,et al.Is estrogen receptorαkey to controlling bones.resistance to fracture?[J].J Endocrinol,2004,182(2):183-191.
[3]WUTTKE W,JARRY H,HAUNSCHILD J,et al.The non-estrogenic alternative for the treatment of climacteric complaints:Black cohosh(Cimicifuga or Actaea racemosa)[J].J Steroid Biochem Mol Biol,2014,139(1):302-310.
[4]ZUCCHINI G,ARMSTRONG A C,WARDLEY A M,et al.Aphase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition[J].Eur J Cancer,2015,51(18):2725-2731.
[5]刘立朝,樊继援.雷洛昔芬对去卵巢大鼠骨组织雌激素受体α表达水平的调节[J].中华骨质疏松和骨矿盐疾病杂志,2013,6(2):161-164.
[6]WEI Q S,HUANG L,TAN X,et al.Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women[J].Scand J Clin Lab Invest,2016,76(1):33-39.
[7]WEI Q S,WANG H B,WANG J L,et al.Combination treatment with whole body vibration and a kidney-tonifying herbal Fufang prevent osteoporosis in ovariectomized rats[J].Orthop Surg,2015,7(1):57-65.
[8]DENG W M,WEI Q S,TAN X,et al.Relation of serum 25 hydroxyvitamin D levels to bone mineral density in southern Chinese postmenopausal women:A preliminary study[J].Indian JMed Res,2015,142(4):430-437.
[9]ZHU H,JIANG J,WANG Q,et al.Associations between ERα/βgene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women:a systematic review and meta-analysis[J].BMC Endocr Disord,2018,18(1):11.
[10]ZHANG L,WONG J,VANACKER J M.The estrogen-related receptors(ERRs):potential targets against bone loss[J].Cell Mol Life Sci,2016,73(20):3781-3787.
[11]彭珊,欧阳厚淦,赵志冬,等.去卵巢大鼠骨质疏松模型的制备与评价[J].中国骨质疏松杂志,2017,23(10):1327-1329.
[12]KHARODE Y P,SHARP M C,BODINE P V N.Utility of the ovariectomized rat as a model for human osteoporosis in drug discovery[M]//Osteoporosis.New Jersey:Humana Press,2008:111-124.
[13]汤璐璐,邓伟民,苏海容,等.补肾壮骨颗粒对SAMP6小鼠股骨宏观结构及生物力学的影响[J].中国骨质疏松杂志,2018,24(1):91-97.
[14]苏海容,汤璐璐,袁人飞,等.补肾壮骨颗粒通过GH/IGF-1轴影响快速老化小鼠骨密度[J].实用医学杂志,2017,33(15):2459-2464.
[15]JIANG H,BAI W,WANG W,et al.Proteomics in plasma of ovariectomized rats and those exposed to estradiol valerate[J].JSteroid Biochem Mol Biol,2017,178:1-12.
[16]LI T,MA Y,ZHANG H,et al.Differential regulation of morphology and estrogen receptor-alpha expression in the vagina of ovariectomized adult virgin rats by estrogen replacement:a histological study[J].Int J Endocrinol,2016,2016(1):1-8.