首页|基于HIF-1α/VEGF通路探讨续苓健骨方对去卵巢大鼠骨代谢和局部血管生成的影响

基于HIF-1α/VEGF通路探讨续苓健骨方对去卵巢大鼠骨代谢和局部血管生成的影响

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目的 基于低氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)通路探讨续苓健骨方对去卵巢大鼠骨代谢和局部血管生成的影响.方法 将24只3月龄大鼠随机分为假手术组、模型组、续苓组和雌二醇组,每组6只.假手术组大鼠仅摘除双侧卵巢周围部分脂肪,其余3组均摘除双侧卵巢.摘除1周后,续苓组按体质量1 mL/(100 g·d)灌胃含生药浓度1.5 g/mL续苓健骨方药液,雌二醇组按体质量1 mL/(100 g·d)灌胃0.0125 mg/mL雌二醇药液,假手术组、模型组给予等体积生理盐水灌胃,每日1次.干预12周后检测4组大鼠左胫骨近端骨密度、左股骨远端骨小梁面积百分比(Tb.Ar%)、骨小梁宽度(Tb.Wi)、骨小梁间距(Tb.Sp)以及血清雌二醇(E2)、Ⅰ型前胶原氨基端原肽(P1NP)、Ⅰ型胶原交联C末端肽(S-CTX)水平,免疫组化法检测4组大鼠左股骨远端分化决定簇抗原31(CD31)、HIF-1α、VEGF蛋白表达水平.结果 与假手术组比较,模型组左胫骨近端骨密度下降(P<0.05),左股骨远端Tb.Wi变化无统计学意义(P>0.05),Tb.Ar%降低,Tb.Sp变大,血清E2、P1NP水平降低,S-CTX水平上升,左股骨远端HIF-1α、VEGF蛋白表达水平显著下降(P均<0.05);与模型组比较,续苓组、雌二醇组左胫骨近端骨密度增高(P<0.05),左股骨远端Tb.Wi变化无统计学意义(P>0.05),Tb.Ar%增高,Tb.Sp缩小,血清E2、P1NP水平升高,续苓组S-CTX水平下降(P均<0.05),续苓组和雌二醇组大鼠左股骨远端CD31、HIF-1α、VEGF蛋白表达水平均显著增高(P均<0.05);续苓组与雌二醇组比较,上述指标差异均无统计学意义(P>0.05).结论 续苓健骨方能上调股骨远端骨组织HIF-1α/VEGF表达,促进血管生成及骨形成,从而稳定骨代谢,减少去卵巢大鼠的骨丢失.
Effects of Xuling-Jiangu Decoction on Bone Metabolism and Local Angiogenesis in Ovariectomized Rats
Objective:To explore the effect of Xuling-Jiangu decoction on bone metabolism and local angiogenesis in ovariecto-mized rats through hypoxia inducible Factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:Twenty four 3-month-old rats were randomly divided into sham operation group,model group,Xuling group and estradiol group,with 6 rats in each group.Only part of the fat around both ovaries were removed in the sham operation group,and both ovaries were removed in the other three groups.One week after removal,the Xuling group was given 1 mL/(100 g·d)solution containing 1.5 g/mL crude drug by gavage,and the estradiol group was given 1 mL/(100 g·d)solution containing 0.0125 mg/mL estradiol by gavage,the sham operation group and the model group were given the same amount of saline by gavage,once a day.After 12 weeks of intervention,bone mineral density of the left tibia was detected,trabecular area percentage(Tb.Ar%)and trabecular width(Tb.Wi)and trabecular separation(Tb.Sp)of the left distal femur were measured.Serum levels of estradiol(E2),Procollagen I N-terminal Propeptide(P1NP)and type I col-lagen cross-linked C-terminal peptide(S-CTX)were detected.The expression levels of differentiation determinant antigen 31(CD31),HIF-1α and VEGF were detected by immunohistochemistry.Results:Compared with sham operation group,bone mineral density of the left proximal tibia in the model group decreased significantly(P<0.01),Tb.Wi of the left distal femur had no significant change(P>0.05),Tb.Ar%decreased,Tb.Sp increased significantly,E2 and P1NP levels in model group decreased,while S-CTX levels in-creased,the expression levels of HIF-1α and VEGF in the left distal femur significantly decreased(P<0.05).Compared with the mod-el group,bone mineral density of rats in the Xuling group and the estradiol group increased,Tb.Wi had no significant change(P>0.05),Tb.Ar%increased and Tb.Sp decreased,serum E2 and P1NP levels increased(P<0.05),while S-CTX decreased only in the Xul-ing group(P<0.05).The expression levels of CD31,HIF-1α and VEGF in left distal femur of the Xuling and estradiol groups signifi-cantly increased(P<0.05).There were no significant differences in the above indexes between the Xuling and estradiol groups(P>0.05).Conclusion:Xuling-Jiangu decoction can up-regulate HIF-1α/VEGF expression in distal femur bone tissue,promote angio-genesis and bone formation,stabilize bone metabolism,and reduce bone loss in ovariectomized rats.

osteoporosisangiogenesisbone metabolismHIF-1α/VEGFXuling-Jiangu decoction

谢冰颖、李生强、林若慧、黄小彬、黄景文、谢丽华、葛继荣

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福建中医药大学中医学院,福建 福州 350122

福建省中医药科学院,福建 福州 350003

福建省中西医结合防治骨质疏松重点实验室,福建 福州 350003

骨质疏松 血管生成 骨代谢 HIF-1α/VEGF 续苓健骨方

福建省自然科学基金项目福建省中医药科研项目

2021J019152021zylc42

2024

福建中医药
福建省中医药学会 福建中医药大学

福建中医药

影响因子:0.518
ISSN:1000-338X
年,卷(期):2024.55(1)
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