培哚普利对卵巢去势大鼠骨质疏松的作用及其机制
|
摘要
目的探讨培哚普利改善卵巢去势大鼠骨质疏松的作用及其机理。方法 50只SD大鼠分为正常对照组、假手术组、卵巢去势组、培哚普利组、雌激素组各10只,假手术组大鼠切除双侧卵巢周边脂肪组织,卵巢去势组、培哚普利组和雌激素组大鼠摘除双侧卵巢,正常对照组大鼠不做处理。卵巢摘除后第5周,培哚普利组大鼠给予培哚普利4mg/kg灌胃,雌激素组大鼠给予戊酸雌二醇胺1.2mg/kg灌胃,正常对照组、假手术组和卵巢去势组大鼠给予相同体积蒸馏水灌胃,均1次/d,持续12周。12周后取各组大鼠左侧股骨采用双能X线骨密度测定仪测量骨密度,取右侧股骨采用实时荧光定量PCR法检测骨组织Wnt3a、LRP5、β-catenin mRNA表达水平。结果雌激素组左侧股骨骨密度值(0.263±0.002)高于培哚普利组(0.131±0.023)、卵巢去势组(0.053±0.002)、假手术组(0.165±0.003)和正常对照组(0.133±0.002)(P<0.01),正常对照组、假手术组、培哚普利组高于卵巢去势组(P<0.05);雌激素组右侧股骨组织Wnt3a、LRP5、β-catenin mRNA表达水平(4.6±0.3、1.0±0.1、0.258±0.004)明显高于卵巢去势组(1.0±0.2、0.3±0.1、0.057±0.002)和培哚普利组(3.1±0.7、0.4±0.2、0.165±0.003),培哚普利组高于卵巢去势组(P<0.05)。结论培哚普利可增加卵巢去势大鼠骨密度,其机制可能是通过上调Wnt3a/LRP5/β-catenin而促进前成骨细胞增殖和分化,从而促进骨形成。
Objective To investigate the role and mechanism of perindopril in improving osteoporosis in ovariectomized rats.Methods Fifty rats were divided into normal control group,sham operation group,ovariectomized group,perindopril group and estrogen(E2)group,with 10 rats in each group.Sham operation group was excised bilateral ovarian peripheral adipose,ovariectomy group,perindopril group and estrogen group were excised bilateral ovaries,while normal control group was not treated.In 5 weeks after ovariectomy,perindopril group was intragastrically administrated with perindopril 4 mg/kg,E_2 group was intragastrically administrated with estrogen 1.2 mg/kg,while normal control group,sham group and ovariectomized group were given an equivalent volume of distilled water,once a day,totally for 12 weeks.After 12 weeks of drugs intervention,the left femur of rats in each group was scanned by dual-energy X-ray absorptiometry and bone mineral density analysis software.The expressions of Wnt3 a,LRP5 andβ-catenin mRNA in bone tissue were detected by real-time fluorescence quantitative PCR.Results The bone mineral density in the left femur was significantly higher in E_2 group(0.263±0.002)than that in perindopril group(0.131±0.023),ovariectomized group(0.053±0.002),sham operation group(0.165±0.003)and normal control group(0.133±0.002)(P<0.01),and higher in normal control group,sham operation group and perindopril group than that in ovariectomized group(P<0.05).The expressions of Wnt3 a,LRP5 andβ-catenin mRNA in right femoral tissue were significantly higher in E_2 group(4.6±0.3,1.0±0.1,0.258±0.004)than those in ovariectomized group(1.0±0.2,0.3±0.1,0.057±0.002)and perindopril group(3.1±0.7,0.4±0.2,0.165±0.003),and higher in perindopril group than those in ovariectomized group(P<0.05).Conclusion Perindopril can increase the bone density in ovariectomized rats,probably by promoting the proliferation and differentiation of preosteoblasts by up-regulating the mRNA expression of Wnt3 a/LRP5/β-catenin so as to promote bone formation.
Objective To investigate the role and mechanism of perindopril in improving osteoporosis in ovariectomized rats.Methods Fifty rats were divided into normal control group,sham operation group,ovariectomized group,perindopril group and estrogen(E2)group,with 10 rats in each group.Sham operation group was excised bilateral ovarian peripheral adipose,ovariectomy group,perindopril group and estrogen group were excised bilateral ovaries,while normal control group was not treated.In 5 weeks after ovariectomy,perindopril group was intragastrically administrated with perindopril 4 mg/kg,E_2 group was intragastrically administrated with estrogen 1.2 mg/kg,while normal control group,sham group and ovariectomized group were given an equivalent volume of distilled water,once a day,totally for 12 weeks.After 12 weeks of drugs intervention,the left femur of rats in each group was scanned by dual-energy X-ray absorptiometry and bone mineral density analysis software.The expressions of Wnt3 a,LRP5 andβ-catenin mRNA in bone tissue were detected by real-time fluorescence quantitative PCR.Results The bone mineral density in the left femur was significantly higher in E_2 group(0.263±0.002)than that in perindopril group(0.131±0.023),ovariectomized group(0.053±0.002),sham operation group(0.165±0.003)and normal control group(0.133±0.002)(P<0.01),and higher in normal control group,sham operation group and perindopril group than that in ovariectomized group(P<0.05).The expressions of Wnt3 a,LRP5 andβ-catenin mRNA in right femoral tissue were significantly higher in E_2 group(4.6±0.3,1.0±0.1,0.258±0.004)than those in ovariectomized group(1.0±0.2,0.3±0.1,0.057±0.002)and perindopril group(3.1±0.7,0.4±0.2,0.165±0.003),and higher in perindopril group than those in ovariectomized group(P<0.05).Conclusion Perindopril can increase the bone density in ovariectomized rats,probably by promoting the proliferation and differentiation of preosteoblasts by up-regulating the mRNA expression of Wnt3 a/LRP5/β-catenin so as to promote bone formation.
引文
[1] ZHANG Y,WANG K,SONG Q,et al.Role of the local bone reninangiotensin system in steroid induced osteonecrosis in rabbits[J].Mol Med Rep,2014,9(4):1128-1134.
[2]周奕,薛青,萧松建.培哚普利对绝经后骨质疏松症伴高血压患者骨转换影响研究[J].中国实用内科杂志,2015,35(10):859-861.
[3]钟奕,薛青,周奕,等.培哚普利对维甲酸所致骨质疏松模型大鼠骨代谢的影响[J].中国组织工程研究,2016,20(18):2589-2595.
[4] CASTROP H,HOCHERL K,KURTZ A,et al.Physiology of kidney renin[J].Physiol Rev,2010,90(2):607-673.
[5]曹源,朱致惠.雌激素替代疗法对绝经后妇女血清血管紧张素转化酶及血脂代谢的影响[J].岭南心血管病杂志,2000,6(4):242-244.
[6]张廷星,晋学庆,吴可贵,等.雌激素对SD大鼠肾素血管紧张素醛固酮系统的影响[J].中华心血管病杂志,2004,32(S2):615-616.
[7]潘海,李晓敏,张岩.雌激素缺乏上调大鼠肾脏肾素和血管紧张素转化酶的表达[J].基础医学与临床,2015,35(2):234-236.
[8] BODINEPV, KOMMBS. Wntsignalingand osteoblastogenesis[J].Rev Endocr Metab Disord,2006,7(1/2):33-39.
[9] SHI Y C,WORTON L,ESTEBANET L,et al.Effects of continuous activation of vitamin D and Wnt response pathways on osteoblastic proliferation and differentiation[J].Bone,2007,41(1):87-96.
[10] BURGERS T A,WILLIAMS B O.Regulation of Wnt/betacatenin signaling within and from osteocytes[J].Bone,2013,54(2):244-249.
[11] MAGGIO M,CEDA G P,LAURETANI F,et al.Relation of angiotensin-converting enzyme inhibitor treatment to insulinlike growth factor-1serum levels in subjects>65years of age[J].Am J Cardiol,2006,97(10):1525-1529.
[12]郭玲,郑立舸,王敏,等.小鼠成骨细胞Wnt信号通路相关因子表达与胰岛素样生长因子1的影响[J].中国组织工程研究与临床康复,2011,15(28):5169-5172.
[13]徐轶尔,孙贵才,于雪峰,等.Wnt信号传导途径与骨质疏松[J].中国骨质疏松杂志,2016,22(2):228-232.
[14]景春贝,汪艳芳,赵志刚,等.中老年2型糖尿病患者血清骨硬化蛋白和体脂肪率与骨骼的相关性[J].中华实用诊断与治疗杂志,2016,30(4):378-380.
[15]高延征,高坤,钟楚楠,等.去卵巢后大鼠骨组织核激活因子受体配体、骨保护素蛋白表达及其与骨质疏松的相关性研究[J].中华实用诊断与治疗杂志,2009,23(3):237-239.
[2]周奕,薛青,萧松建.培哚普利对绝经后骨质疏松症伴高血压患者骨转换影响研究[J].中国实用内科杂志,2015,35(10):859-861.
[3]钟奕,薛青,周奕,等.培哚普利对维甲酸所致骨质疏松模型大鼠骨代谢的影响[J].中国组织工程研究,2016,20(18):2589-2595.
[4] CASTROP H,HOCHERL K,KURTZ A,et al.Physiology of kidney renin[J].Physiol Rev,2010,90(2):607-673.
[5]曹源,朱致惠.雌激素替代疗法对绝经后妇女血清血管紧张素转化酶及血脂代谢的影响[J].岭南心血管病杂志,2000,6(4):242-244.
[6]张廷星,晋学庆,吴可贵,等.雌激素对SD大鼠肾素血管紧张素醛固酮系统的影响[J].中华心血管病杂志,2004,32(S2):615-616.
[7]潘海,李晓敏,张岩.雌激素缺乏上调大鼠肾脏肾素和血管紧张素转化酶的表达[J].基础医学与临床,2015,35(2):234-236.
[8] BODINEPV, KOMMBS. Wntsignalingand osteoblastogenesis[J].Rev Endocr Metab Disord,2006,7(1/2):33-39.
[9] SHI Y C,WORTON L,ESTEBANET L,et al.Effects of continuous activation of vitamin D and Wnt response pathways on osteoblastic proliferation and differentiation[J].Bone,2007,41(1):87-96.
[10] BURGERS T A,WILLIAMS B O.Regulation of Wnt/betacatenin signaling within and from osteocytes[J].Bone,2013,54(2):244-249.
[11] MAGGIO M,CEDA G P,LAURETANI F,et al.Relation of angiotensin-converting enzyme inhibitor treatment to insulinlike growth factor-1serum levels in subjects>65years of age[J].Am J Cardiol,2006,97(10):1525-1529.
[12]郭玲,郑立舸,王敏,等.小鼠成骨细胞Wnt信号通路相关因子表达与胰岛素样生长因子1的影响[J].中国组织工程研究与临床康复,2011,15(28):5169-5172.
[13]徐轶尔,孙贵才,于雪峰,等.Wnt信号传导途径与骨质疏松[J].中国骨质疏松杂志,2016,22(2):228-232.
[14]景春贝,汪艳芳,赵志刚,等.中老年2型糖尿病患者血清骨硬化蛋白和体脂肪率与骨骼的相关性[J].中华实用诊断与治疗杂志,2016,30(4):378-380.
[15]高延征,高坤,钟楚楠,等.去卵巢后大鼠骨组织核激活因子受体配体、骨保护素蛋白表达及其与骨质疏松的相关性研究[J].中华实用诊断与治疗杂志,2009,23(3):237-239.