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

作　　者：王宏伟[1] 卜晓洁 战祥芹 陈福莲[2] 王燕 杨延民[1] WANG Hongwei;BU Xiaojie;ZHAN Xiangqin;CHEN Fulian;WANG Yan;YANG Yanmin(Department of Health and Geriatrics,Rizhao People’s Hospital of Shandong Provience,Rizhao 276800,China;Department of Endocrinology,Weifang Yidu Central Hospital,Weifang 262500,China;Department of Endocrinology,the Second Affiliated Hospital of Shandong First Medical University,Taian 271000,China)

机构地区：[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

出　　处：《中国骨质疏松杂志》2023年第9期1285-1291,共7页Chinese Journal of Osteoporosis

基　　金：山东省医药卫生科技发展计划项目(202103061110)。

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 1μg/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。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-αdecreased 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.

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 

分 类 号：R589.5[医药卫生—内分泌]