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Effects of Compound Qishen Extract on Wound Healing and HIF-1α/VEGF/VEGFR2 Pathway in Diabetic Foot Ulcer Model Rats |
YU Zeyang, LI Tianbo, WANG Jiangning |
Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, China |
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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.
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[1] Barnes JA,Eid MA,Creager MA,et al.Epidemiology and risk of amputation in patients with diabetes mellitus and peripheral artery disease[J]. Arterioscler Thromb Vasc Biol,2020,40(8):1808~1817. [2] 景晓莉. 高原低氧环境下2型糖尿病患者血清HIF-1α、VEGF与尿液smad1表达的相关性分析[J].中国实验诊断学,2020,24(6):945~948. [3] Xia X,Wang S,Ni B,et al.Hypoxic gastric cancer-derived exosomes promote progression and metastasis via MiR-301a-3p/PHD3/HIF-1α positive feedback loop[J]. Oncogene,2020,39(39):6231~6244. [4] 张晓玲,陈剑,姚敏,等.HIF-1α的RNA干涉可引起缺氧条件下人角膜上皮细胞VEGF表达下调和PEDF表达上调[J].细胞与分子免疫学杂志,2018,34(10):880~884. [5] Jiang S,Gao Y,Yu QH,et al.P-21-activated kinase 1 contributes to tumor angiogenesis upon photodynamic therapy via the HIF-1α/VEGF pathway[J]. Biochem Biophys Res Commun,2020,526(1):98~104. [6] 雷霆,孙东旭,周军,等.基于Wnt/β-catenin信号通路的三七/白及胶海绵促进糖尿病足溃疡模型大鼠创面愈合的作用机制研究[J].中国药房,2019,30(4):483~487. [7] 李博文,金珏安,徐磊,等.生肌象皮膏对糖尿病足溃疡大鼠创面愈合及Notch信号通路的影响[J].中国药师,2019,22(9):1634~1638. [8] 乐暾,王蕾,李晶,等.金鸡毛草水提物对糖尿病足模型大鼠的作用[J].中国实验方剂学杂志,2018,24(8):134~139. [9] Wu C,Chen W,Fang M,et al.Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocellular carcinoma progression via miR-145/miR-21 mediated Smad3 phosphorylation[J].Ethnopharmacol,2019,231(1):98~112. [10] 张彦,汪天赐,蔡婧,等.表没食子儿茶素没食子酸酯促进2型糖尿病伤口愈合的实验研究[J].安徽医药,2020,24(9):1712~1718. [11] Nie T,Zhao S,Mao L,et al.The natural compound,formononetin,extracted from astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity[J]. Br Pharmacol,2018,175(9):1439~1450. [12] Wu M,Liu Y,Zhang H,et al.Intravenous injection of l-aspartic acid β-hydroxamate attenuates choroidal neovascularization via anti-VEGF and anti-inflammation[J]. Exp Eye Res,2019,182(1):93~100. [13] Lin CJ,Lan YM,Ou MQ,et al.Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats[J].Endocrinol Invest,2019,42(11):1307~1317. [14] Zhu Y,Wang Y,Jia Y,et al.Roxadustat promotes angiogenesis through HIF-1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats[J]. Wound Repair Regen,2019,27(4):324~334. [15] Gao W,Sun L,Fu X,et al.Enhanced diabetic wound healing by electrospun core-sheath fibers loaded with dimethyloxalylglycine[J].Mater Chem B,2018,6(2):277~288. |
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