Vaspin对去卵巢大鼠骨质疏松的保护作用及机制研究
Protective effect and mechanism of vaspin on osteoporosis in ovariectomized rats
  
DOI:10.3969/j.issn.1006-7108.2023.09.007
中文关键词:  内脏脂肪组织特异性丝氨酸蛋白酶抑制剂  绝经后骨质疏松症  去卵巢大鼠  OPG/RANKL信号通路  骨代谢
英文关键词:visceral adipose tissue specific serine protease inhibitors  postmenopausal osteoporosis  ovariectomized rats  OPG/RANKL signaling pathway  bone metabolism
基金项目:山东省医药卫生科技发展计划项目(202103061110)
作者单位
王宏伟1 卜晓洁1 战祥芹1 陈福莲2 王燕3 杨延民1* 1.山东省日照市人民医院保健/老年医学科山东 日照 276800 2.山东省潍坊市益都中心医院山东 潍坊 262500 3.山东第一医科大学第二附属医院内分泌科, 山东 泰安 271000 
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中文摘要:
      目的 观察内脏脂肪组织特异性丝氨酸蛋白酶抑制剂(visceral adipose tissue derived serine protease inhibitor,Vaspin)对去卵巢大鼠骨质疏松的保护作用,并探讨潜在的机制。方法 30只雌性SD大鼠随机分为假手术组(Sham)、去卵巢组(OVX)以及OVX+Vaspin治疗组,每组10只,OVX组及OVX+Vaspin治疗组均给予去卵巢手术构建绝经后骨质疏松模型,OVX+Vaspin组大鼠每天给予Vaspin 1 μg/kg腹腔注射治疗,Sham及OVX组给予等量生理盐水腹腔注射,干预12周后,检测血清1型胶原前N末端前肽(P1NP)、骨钙素(OCN)、抗酒石酸酸性磷酸酶(TRAP)、1型胶原C末端肽(CTX)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)的水平;再分别进行骨病理组织学检查、生物力学分析、microCT检查,评价骨微观结构和骨强度,并通过qRT-PCR和Western blot检测Vaspin对骨组织中OPG及RANKL的mRNA和蛋白表达的影响。结果 Vaspin干预治疗12周后,与OVX组相比,OVX+Vaspin组大鼠的血清P1NP和OCN明显升高,血清TRAP、CTX及IL-1β、TNF-α明显降低(P<0.05),骨强度和显微结构特征改善, 大鼠骨组织中OPG的mRNA和蛋白表达水平均上调,RANKL的mRNA和蛋白表达水平均下调。结论 Vaspin可能通过上调OPG的表达、下调RANKL的表达介导对OVX大鼠骨代谢的调节作用,改善骨微观结构和提高骨强度,从而发挥抗骨质疏松的作用。
英文摘要:
      Objective To observe the protective effect of visceral adipose tissue derived serine protease inhibitor (vaspin) on osteoporosis in ovariectomized rats, and to explore the potential mechanism. Methods Thirty female SD rats were randomly divided into sham group (Sham), OVX group (OVX), and OVX+vaspin group, with 10 rats in each group. Rats in OVX group and OVX+vaspin group were performed ovariectomy to construct postmenopausal osteoporosis model. Rats in OVX+vaspin group received intraperitoneal injection of 1μg/kg vaspin every day, while rats in Sham and OVX groups received intraperitoneal injection of the same amount of normal saline. After 12 weeks of intervention, serum concentrations of type 1 collagen pron-terminal propeptide (P1NP), osteocalcin (OCN), tartrate-resistant acid phosphatase (TRAP), type 1 collagen C-terminal peptide (CTX), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected. Then histological examination, biomechanical analysis, and micro-CT examination were performed to evaluate bone microstructure and bone strength. The effects of vaspin on mRNA and protein expressions of OPG and RANKL in the bone tissue were detected using qRT-PCR and Western blotting. Results After 12 weeks of vaspin intervention, compared those in OVX group, serum P1NP and OCN in OVX+vaspin group increased significantly, while serum TRAP, CTX, IL-1β, and TNF-α decreased significantly (P<0.05). The mRNA and protein expression levels of OPG and RANKL in the bone tissue of the OVX group were respectively up-regulated and down-regulated compared to those in OVX group. Conclusion Vaspin may regulate bone metabolism in OVX rats by up-regulating the expression of OPG and down-regulating the expression of RANKL, improving bone microstructure and bone strength, and thus play an anti-osteoporosis role.
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