摘要
目的探究虎杖苷对骨质疏松性骨折大鼠骨折愈合的效果及对沉默信息调节因子1(SIRT1)/叉头状转录因子O1(FoxO1)信号通路的影响。方法构建骨质疏松性骨折大鼠模型,将建模成功的48只大鼠随机分为模型组、虎杖苷低剂量(30 mg/kg)组、虎杖苷高剂量(60 mg/kg)组、阿仑膦酸钠组(0.5 mg/kg)。另取12只大鼠作为对照组,构建相同部位骨折模型。建模结束后,各组大鼠给予相应药物灌胃,每天1次,连续8周。对大鼠进行骨折愈合程度评分并检测骨折处骨密度(bone mineral density,BMD);运用酶联免疫吸附法检测大鼠血清中I型胶原交联羧基末端肽(CTX-Ⅰ)、骨钙素(OC)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平;通过苏木素-伊红染色观察大鼠骨组织病理学;通过荧光定量PCR法检测大鼠骨组织中SIRT1、FoxO1信使RNA(mRNA)水平;通过蛋白印迹法检测大鼠骨组织中SIRT1、FoxO1蛋白水平。结果与模型组相比,虎杖苷低、高剂量组大鼠骨组织病理学变化程度依次减轻,骨折愈合程度评分、骨折处BMD、血清中OC、骨组织中SIRT1、FoxO1 mRNA和蛋白水平依次升高,CTX-Ⅰ、TNF-α、IL-1β水平依次降低(P<0.05);阿仑膦酸钠组和虎杖苷高剂量组大鼠骨组织病理学变化及各项指标比较均无显著差异(P>0.05)。结论虎杖苷可减轻骨质疏松性骨折大鼠炎症反应,提升BMD,促进骨折愈合,其机制可能与激活SIRT1/FoxO1信号通路有关。
Objective To investigate the effect of polydatin on fracture healing in rats with osteoporotic fracture and its effect on silent information regulator 1(SIRT1)/forkhead transcription factor O1(FoxO1)signaling pathway.Methods A rat model of osteoporotic fracture was established,and 48 rats with successful modeling were randomly divided into model group,polydatin low(30 mg/kg),high(60 mg/kg)dose groups,and alendronate sodium(0.5 mg/kg)group.Another 12 rats were taken as control group to construct the fracture model of the same site.After modeling,the rats in each group were given the corresponding drugs by gavage once a day for 8 weeks.Fracturehealing score and bone mineral density(BMD)at fracture site were performed in rats;enzyme linked immunosorbent assay was used to measure the serum levels of C-telopeptide of type I collagen(CTX-Ⅰ),osteocalcin(OC),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β);HE staining was used to observe the pathological changes of bone tissue;the mRNA levels of SIRT1 and FoxO1 in bone tissue were detected by fluorescence quantitative PCR;Western blot was used to detect the protein levels of SIRT1 and FoxO1 in bone tissue.Results Compared with model group,the pathological changes of bone tissue in thepolydatin low and high dose groups were gradually alleviated,the fracture healing score,BMD at the fracture site,the levels of OCin serum,and mRNA and protein levels of SIRT1 and FoxO1 in bone tissue were increased successively,CTX-Ⅰ,TNF-α,IL-1βlevels was decreased successively(P<0.05);there were no significant differences in bone pathological changes and various indexes between alendronate sodium group and polydatin high dose group(P>0.05).Conclusion Polydatin can reduce inflammatory response,improve BMD and promote fracture healing in rats with osteoporotic fracture,and its mechanism may be related to the activation of SIRT1/FoxO1 signaling pathway.
作者
李明哲
罗国厂
张仲博
岳宗进
LI Mingzhe;LUO Guochang;ZHANG Zhongbo;YUE Zongjin(Nanyang Medical College,Nanyang 473000;Henan Provincial Hospital of Traditional Chinese Medicine,Zhengzhou 450000,China)
出处
《中国骨质疏松杂志》
CAS
CSCD
北大核心
2023年第8期1154-1159,共6页
Chinese Journal of Osteoporosis
基金
河南省高等职业院校创新发展行动计划项目(XM-17-439)。
