复方芪参提取物对糖尿病足溃疡模型大鼠创面愈合及HIF-1α/VEGF/VEGFR2通路的影响

doi:10.3969/j.issn.1006-6233.2021.03.005

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摘要目的探讨复方芪参提取物对糖尿病足溃疡模型大鼠创面愈合及缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)/血管内皮生长因子受体2(VEGFR2)通路的影响。方法建立糖尿病足溃疡大鼠模型,将造模成功48只大鼠随机分为模型组、二甲双胍组(0.2g/kg)、复方芪参提取物低剂量组(4g/kg)、复方芪参提取物高剂量组(8g/kg),每组12只;12只正常大鼠以相同方法建立溃疡创面伤口作为对照组。造模成功后第1天,二甲双胍组、复方芪参提取物低剂量组、复方芪参提取物高剂量组分别灌胃0.2g/kg二甲双胍、4g/kg、8g/kg复方芪参提取物,对照组和模型组灌胃等体积生理盐水,每天1次,连续灌胃4周。给药周期结束后,测定大鼠溃疡创面愈合率,观察糖尿病足大鼠和正常大鼠溃疡创面组织病理改变,测定糖尿病足大鼠和正常大鼠溃疡创面组织中HIF-1α、VEGF、VEGFR2 mRNA和蛋白水平。结果对照组创面组织结构正常,可见大量成纤维细胞及毛细血管;模型组创面组织大量炎症细胞浸润,成纤维细胞及毛细血管数目明显减少;二甲双胍和复方芪参提取物干预后,创面组织成纤维细胞及毛细血管增加,炎症细胞浸润减少。与对照组比较,模型组大鼠创面愈合率、溃疡创面组织HIF-1α、VEGF、VEGFR2 mRNA和蛋白水平降低(P<0.05);与模型组比较,二甲双胍组、复方芪参提取物低、高剂量组大鼠创面愈合率、溃疡创面组织HIF-1α、VEGF、VEGFR2 mRNA和蛋白水平升高(P<0.05);复方芪参提取物高剂量组大鼠创面愈合率、溃疡创面组织HIF-1α、VEGF、VEGFR2 mRNA和蛋白水平高于复方芪参提取物低剂量组(P<0.05);与二甲双胍组比较,复方芪参提取物低剂量组大鼠上述指标降低(P<0.05);复方芪参提取物高剂量组与二甲双胍组大鼠上述指标差异无统计学意义(P>0.05)。结论复方芪参提取物可促进糖尿病足溃疡模型大鼠创面愈合,其机制可能与复方芪参提取物促进大鼠糖尿病足溃疡创面组织中HIF-1α、VEGF、VEGFR2 mRNA和蛋白表达,进而激活HIF-1α/VEGF/VEGFR2通路有关。

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	于泽洋
	李天博
	王江宁

关键词 ：复方芪参提取物, 糖尿病足溃疡, HIF-1α, /VEGF/VEGFR2通路

Abstract：Objective: To investigate the effect of compound Qishen extract on wound healing and hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) pathway in diabetic foot ulcer model rats. Methods: To establish diabetic foot ulcer rat model,forty-eight rats were successfully established and randomly divided into model group,metformin group (0.2g/kg),compound Qishen extract low dose group (4g/kg),compound Qishen extract high dose group (8g/kg),12 rats in each group; 12 normal rats were used to establish ulcer wound as control group. On the first day after successful modeling,metformin group,compound Qishen extract low dose group and compound Qishen extract high dose group were given 0.2g/kg metformin,4g/kg and 8g/kg compound Qishen extract respectively,and the control group and model group were intragastrically given the same volume of normal saline,once a day for 4 weeks. At the end of the administration period,the healing rate of ulcer wound was measured,the pathological changes of ulcer wound tissue in diabetic foot rats and normal rats were observed,and the levels of HIF-1α,VEGF,VEGFR2 mRNA and protein in ulcer wound tissues of diabetic foot rats and normal rats were measured. Results: In the control group,the wound tissue structure was normal,with a large number of fibroblasts and capillaries; in the model group,a large number of inflammatory cells infiltrated,and the number of fibroblasts and capillaries decreased significantly; after the intervention of metformin and compound Qishen extract,the wound tissue fibroblasts and capillaries increased,and the inflammatory cell infiltration decreased. Compared with the control group,the wound healing rate,ulcer wound tissue HIF-1α,VEGF,VEGFR2 mRNA and protein levels in the model group were decreased (P<0.05); compared with the model group,the wound healing rate,ulcer wound tissue HIF-1α,VEGF,VEGFR2 mRNA and protein levels in the metformin group and the low and high dose groups of compound Qishen extract were increased (P<0.05); the wound healing rate,ulcer wound tissue HIF-1α,VEGF,VEGFR2 mRNA and protein levels in compound Qishen extract high dose group were higher than those in compound Qishen extract low dose group (P<0.05); compared with metformin group,the above indexes of rats in the compound Qishen extract low dose group were lower (P<0.05); but there was no significant difference between the two groups (P>0.05); there was no significant difference between the compound Qishen extract high dose group and metformin group (P>0.05). Conclusion: Compound Qishen extract can promote wound healing of diabetic foot ulcer model rats,and its mechanism may be related to the promotion of HIF-1 α,VEGF,VEGFR2 mRNA and protein levels by Compound Qishen extract,and then activate HIF-1α/VEGF/VEGFR2 pathway.

Key words： Compound Qishen extract Diabetic foot ulcer HIF-1α/VEGF/VEGFR2 pathway;

基金资助:北京市科技计划课题,(编号:Z171100001017070)

通讯作者: 王江宁

引用本文:

于泽洋, 李天博, 王江宁. 复方芪参提取物对糖尿病足溃疡模型大鼠创面愈合及HIF-1α/VEGF/VEGFR2通路的影响[J]. 河北医学, 2021, 27(3): 374-379.
YU Zeyang, LI Tianbo, WANG Jiangning. Effects of Compound Qishen Extract on Wound Healing and HIF-1α/VEGF/VEGFR2 Pathway in Diabetic Foot Ulcer Model Rats. HeBei Med, 2021, 27(3): 374-379.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2021.03.005 或 http://www.hbyxzzs.cn/CN/Y2021/V27/I3/374

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