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唐林,韦敏克,韦建勋,柳达.血管紧张素Ⅱ受体抑制剂对去卵巢骨质疏松小鼠腰椎骨组织的影响及可能机制[J].脊柱外科杂志,2018,16(3):157-162.
血管紧张素Ⅱ受体抑制剂对去卵巢骨质疏松小鼠腰椎骨组织的影响及可能机制     点此下载全文 (Fulltext)
唐林1  韦敏克1  韦建勋1  柳达2
1. 广西壮族自治区人民医院骨科, 广西壮族自治区 530021;
2. 中国医科大学附属第四医院骨科, 辽宁 110000
基金项目:辽宁省自然科学基金(2013021054)
DOI:10.3969/j.issn.1672-2957.2018.03.007
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摘要:
      目的 探讨血管紧张素Ⅱ受体抑制剂对去卵巢骨质疏松小鼠腰椎骨组织的影响及可能的机制。方法 将60只雌性小鼠随机平均分为假手术组、模型组和氯沙坦治疗组,模型组和氯沙坦治疗组均将小鼠双侧卵巢切除建立骨质疏松模型。术后第7天开始,假手术组和模型组小鼠每天灌服0.5 mL生理盐水,氯沙坦治疗组小鼠按照10 mg (/kg·d)的剂量灌服氯沙坦水溶液0.5 mL。建模后8周和12周时,检测各组小鼠血清中雌二醇、碱性磷酸酶(ALP)、骨钙蛋白(OCN)和Ⅰ型前胶原羧基端前肽(PICP)水平,采用Micro-CT三维成像系统对小鼠腰椎进行骨形态计量学检测,采用实时荧光定量PCR技术检测各组小鼠腰椎组织中骨保护素(OPG)、核因子κB受体活化因子(RANK)和核因子κB受体活化因子配体(RANKL)表达。结果 与假手术组相比,模型组和氯沙坦治疗组小鼠8周、12周时血清雌二醇水平均降低;模型组小鼠8周、12周时血清ALP、OCN和PICP水平均升高;氯沙坦治疗组小鼠8周时血清ALP、OCN和PICP水平均升高;差异均有统计学意义(P<0.05)。与模型组比较,氯沙坦治疗组8周、12周时小鼠血清ALP、OCN和PICP水平差异均降低,差异有统计学意义(P<0.05)。与8周时相比,模型组12周时血清ALP、OCN和PICP水平均升高,氯沙坦治疗组12周时血清ALP、OCN和PICP水平均降低,差异均有统计学意义(P<0.05)。与假手术组相比,模型组和氯沙坦治疗组骨密度(BMD)、骨小梁数量(Tb.N)、骨小梁体积分数(BV/TV)和骨小梁厚度(Tb.Th)均降低,而骨小梁间隙(Tb.Sp)和结构模型指数(SMI)均升高,差异均有统计学意义(P<0.05);与模型组相比,氯沙坦治疗组BMD、Tb.N、BV/TV和Tb.Th均升高,而Tb.Sp和SMI均降低,差异均有统计学意义(P<0.05)。与假手术组相比,模型组和氯沙坦治疗组小鼠腰椎组织中OPG mRNA、RANK mRNA相对表达量均降低,而RANKL mRNA相对表达量和RANKL/OPG比值均升高,差异均有统计学意义(P<0.05);与模型组相比,氯沙坦治疗组小鼠腰椎组织中OPGmRNA、RANK mRNA相对表达量均升高,而RANKL mRNA相对表达量和RANKL/OPG比值均降低,差异均有统计学意义(P<0.05)。结论 血管紧张素Ⅱ受体抑制剂可能通过促进骨形成、抑制骨吸收,减少负转换而导致的骨丢失,从而改善去卵巢骨质疏松小鼠腰椎骨组织骨质疏松状态。
关键词:腰椎  骨质疏松  卵巢  血管紧张素Ⅱ1型受体抑制剂  小鼠
Effects of angiotensin Ⅱ receptor inhibitor on lumbar vertebrae bone tissue in ovariectomized osteoporosis mice and its possible mechanism    Fulltext
TANG Lin1  WEI Min-ke1  WEI Jian-xun1  LIU Da2
1. Department of Orthopaedics, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China;
2. Department of Orthopaedics, Fourth Affiliated Hospital of China Medical University, Shenyang 110000, Liaoning, China
Fund Project:
Abstract:
      Objective To investigate the effects of angiotensin Ⅱ receptor inhibitor on lumbar vertebrae bone tissue in ovariectomized osteoporosis mice and its possible mechanism. Methods Totally 60 female mice were randomly and equally divided into sham group, model group and losartan treatment group, and the ovariectomized models were established in model group and losartan treatment group. From the 7th day after the operation, the mice were given 0.5 mL normal saline daily in the sham group and model group, while 0.5 mL losartan water solvent with the dose of 10 mg/(kg·d) was used in the losartan treatment group. At 8 and 12 weeks after the modeling, the serum levels of estradiol, alkaline phosphatase(ALP), osteocalcin (OCN) and procollagen typeⅠcarboxyterminal propeptide(PICP) were measured. The metrology of the lumbar spine in mice were measured using Micro-CT three-dimensional imaging system. The expressions of osteoprotegerin(OPG), receptor activator of NF-κB(RANK) and receptor activator for nuclear factor-κB ligand(RANKL) in the lumbar vertebrae were detected by realtime quantitative PCR. Results Compared with the sham group, the serum levels of estradiol at 8 weeks and 12 weeks in the model and losartan treatment groups were decreased; the serum levels of ALP, OCN and PICP at 8 weeks and 12 weeks in the model group were increased; the serum levels of ALP, OCN and PICP at 8 weeks in the losartan treatment group were increased; all with statistical significance(P<0.05). Compared with the model group, the serum levels of ALP, OCN and PICP at 8 weeks and 12 weeks in the losartan treatment group were decreased, all with statistical significance(P<0.05). Compared with at 8 weeks, the serum levels of ALP, OCN and PICP at 12 weeks in the model group were increased; the serum levels of ALP, OCN and PICP at 12 weeks in the losartan treatment group were decreased; all with statistical significance(P<0.05). Compared with the sham group, the bone mineral density(BMD), trabecular plate number(Tb.N), trabecular bone volume fraction(BV/TV), and trabecular plate thickness(Tb.Th) in the model and losartan treatment group were decreased, while the trabecular spacing(Tb.Sp) and structure model index(SMI) were increased, all with statistical significance(P<0.05). Compared with the model group, the BMD, Tb.N, BV/TV and Tb.Th in the losartan treatment group were increased, while the Tb.Sp and SMI were decreased, all with statistical significance(P<0.05). Compared with the sham group, the relative expression levels of OPG mRNA and RANK mRNA in the lumbar vertebrae in the model and losartan treatment were decreased, while the relative expression levels of RANKL mRNA and RANKL/OPG ratio were increased, all with statistical significance (P<0.05). Compared with the model group, the relative expression levels of OPG mRNA and RANK mRNA in the lumbar vertebrae in the losartan treatment group were increased, while the relative expression levels of RANKL mRNA and RANKL/OPG ratio were decreased, all with statistical significance(P<0.05). Conclusion Angiotensin Ⅱ receptor inhibitor may improve osteoporosis state in lumbar spine bone tissues in ovariectomized osteoporosis mice through promoting bone formation, inhibiting bone resorption and reducing the bone loss caused by negative conversion.
Keywords:Lumbar vertebrae  Osteoporosis  Ovary  Angiotensin Ⅱ type 1 receptor blockers  Mice
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