首页|鹿茸多肽通过SDF-1α/CXCR4轴调控PI3K/AKT信号通路促进下肢动脉硬化性闭塞症大鼠血管新生的作用机制

鹿茸多肽通过SDF-1α/CXCR4轴调控PI3K/AKT信号通路促进下肢动脉硬化性闭塞症大鼠血管新生的作用机制

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目的:探索鹿茸多肽通过基质细胞衍生因子(SDF-1α)/趋化因子受体(CXCR4)轴对磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶 B(AKT)通路促进下肢动脉硬化性闭塞症(PAD)大鼠血管新生的作用机制。方法:采用结扎并离断大鼠股动脉及分支造成肢体缺血、给予高脂饲料喂养制作大鼠下肢动脉硬化闭塞症模型。将 100只雄性 Sprague Dawley(SD)大鼠随机分为 10组,分别为空白组、模型组、假手术组,鹿茸多肽低剂量组、鹿茸多中剂量肽组、鹿茸多肽高剂量组、抑制剂 LY294002 组、鹿茸多肽低剂量+抑制剂LY294002组、鹿茸多肽中剂量+抑制剂LY294002组、鹿茸多肽高剂量+抑制剂LY294002组。将空白组、模型组及假手术组灌胃等容量蒸馏水。鹿茸多肽低、中、高剂量组+抑制剂LY294002组先行腹腔注射再灌胃,于造模完第 1天开始给药,每日 1次,28d后处死。采用流式细胞术检测给药后外周血、骨髓中造血干细胞(CD34+细胞)比例;免疫荧光法检测给药后患侧腓肠肌 SDF-1α、PI3K的阳性细胞数比例。结果:造血干细胞(CD34+细胞)比例模型组均显著高于空白组(P<0。05);其中鹿茸多肽低剂量组较鹿茸多肽低剂量+抑制剂 LY294002组阳性细胞比例升高,鹿茸多肽中剂量组较鹿茸多肽中剂量+抑制剂 LY294002 组阳性细胞比例升高,鹿茸多肽高剂量组较鹿茸多肽高剂量+抑制剂 LY294002组阳性细胞比例升高(P<0。05);给药组 SDF-1α、PI3K的阳性细胞数高于模型组及抑制组(P<0。05),鹿茸多肽中剂量组高于鹿茸多肽低剂量组(P<0。05),鹿茸多肽高剂量组高于鹿茸多肽高剂量组+ LY294002组(P<0。05)。结论:鹿茸多肽通过 SDF-1α/CXCR4轴影响 PI3K/AKT信号通路促进了内皮祖细胞的增殖及分化、PAD血管新生。
The Mechanism of Antler Polypeptide Regulating PI3K/AKT Signaling Pathway through SDF-1α/CXCR4 Axis Promotes Angiogenesis on Rats with Lower Extremity Arteriosclerotic Obliterans
Objective:To explore the effect of antler polypeptides on phosphatidylinoinosidine-3-kinase(PI3K)/protein kinase B(AKT)pathway through stromal cell derived factor(SDF-1α)/receptor(CXCR4)axis,and to promote angiogenesis on rats with lower limb arteriosclerotic obliterans(PAD).Methods:The rats model with lower extremity arteriosclerosis obliterans were established by ligation and severing of femoral artery and branches to construct limb ischemia and feeding with high fat diet.One hundred male SD rats were randomly divided into blank group,model group and sham operation group;antler polypeptide low dose group,medium dose antler polypeptide medium dose group,antler polypeptide high dose group,inhibitor LY294002 group,LY294002+antler polypeptide low dose group,LY294002+antler polypeptide medium dose group,LY294002+antler polypeptide high dose group.The blank group,model group and sham group were gavaged equal volume of distilled water.LY294002+antler polypeptide low dose group,LY294002+antler polypeptide medium dose group,LY294002+antler polypeptide high dose group were first injected intraperitoneally and then gavaged with intragastric administration,once a day after modeling,and rats,were executed after 28 days.Flow cytometry was used to detect the proportion of hematopoietic stem cells(CD34+cells)in peripheral blood and bone marrow after administration.The proportion of SDF-1α and PI3K positive cells in gastrocnemius muscle was detected by immunofluorescence assay.Results:The proportion of hematopoietic stem cells(CD34+ cells)in model group was higher than that in blank group(P<0.05).The proportion of positive cells in antler polypeptide low dose group was higher than that in LY294002+antler polypeptide low dose group,the proportion of positive cells in antler polypeptide medium dose group was higher than that in LY294002+antler polypeptide medium dose group,and the proportion of positive cells in antler polypeptide high dose group was higher than that in LY294002+antler polypeptide high dose group(P<0.05).The proportion of positive cell number of SDF-1α and PI3K in administration group was significantly higher than that in model group and inhibition group(P<0.05),the antler polypeptide medium dose group was higher than that in LY294002+antler polypeptide medium dose group group,and the antler polypeptide medium dose group was higher than that in antler polypeptide low dose group group(P<0.05),antler polypeptide high dose group was higher than LY294002+antler polypeptide high dose group(P<0.05).Conclusion:Antler polypeptide affected the PI3K/AKT signaling pathway through SDF-1α/receptor(CXCR4)axis thereby promoting the proliferation and differentiation of endothelial progenitor cells,and facilitating the angiogenesis of PAD.

arteriosclerotic obliterans of lower extremityantler polypeptideendothelial progenitor cellsangiogenesisexperimental study

丁爱国、王雁彬、李廷荃、李子娟、王继尧、曹佳颖

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朔州市人民医院(山西朔州 036000)

山西中医药大学附属医院(太原 030024)

山西中医药大学

下肢动脉硬化性闭塞症 鹿茸多肽 内皮祖细胞 血管新生 实验研究

国家自然科学基金山西省自然科学基金国家中医药局中医药领军人才培养项目岐黄学者支持项目

8187447420210302124563

2024

中西医结合心脑血管病杂志
中国中西医结合学会 山西医科大学第一医院

中西医结合心脑血管病杂志

CSTPCD
影响因子:1.463
ISSN:1672-1349
年,卷(期):2024.22(8)
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