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复方芪参提取物促进糖尿病足溃疡大鼠创面修复的机制

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目的 探讨复方芪参提取物对糖尿病足溃疡(DFU)大鼠创面的愈合能力.方法 选取6~8周龄无特定病原体(SPF)级成年SD大鼠(河北省实验动物中心),体重200-250 g,共110只.其中36只作为对照组,其余74只进行高糖高脂饲料喂养,并注射低剂量链脲佐菌素(STZ)诱导糖尿病.成功建立糖尿病足溃疡模型的72只大鼠按随机数字表法分为模型组和复方芪参提取物组,每组36只.通过在大鼠背侧后足打孔形成溃疡创面伤口.复方芪参提取物组大鼠口服复方芪参提取物,模型组和对照组分别口服生理盐水.观察溃疡创面愈合率,并使用酶联免疫吸附试验(ELISA)检测血清中白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的表达水平.免疫组织化学检测溃疡创面组织中表皮生长因子(EGF)、血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)和E-钙黏蛋白(E-cadherin)的表达.计量资料组间差异比较采用单因素方差分析或LSD-t检验,计数资料指标组间比较使用x2检验.结果 模型组大鼠创面愈合率显著低于对照组[(16.84±3.01)%比(43.36±4.42)%,t=8.49,P<0.05];复方芪参提取物组大鼠创面愈合率显著高于模型组[(28.50±2.62)%比(16.84±3.01)%,t=12.48,P<0.05].在第 3、6、9 天的时间点上,模型组 IL-6 水平显著高于对照组(21.29±3.42 比 15.78±3.06,t=-6.23,P<0.05;22.36± 2.98 比 15.69±3.12,t=-4.26,P<0.05;22.58±3.06 比 15.38±2.86,t=-5.45,P<0.05);复方芪参提取物组IL-6水平显著低于模型组(17.99±1.95比21.29±3.42,t=4.23,P<0.05;17.95± 1.87 比 22.36±2.98,t=3.45,P<0.05;18.02±1.82 比 22.58±3.06,t=4.62,P<0.05);模型组TNF-α 水平显著高于对照组(17.18±2.42 比 8.38±0.69,t=-8.44,P<0.05;18.06±3.41 比8.60±1.09,t=-7.29,P<0.05;17.38±2.69 比 8.53±1.06,t=-6.52,P<0.05);复方芪参提取物组 TNF-α 表达水平显著低于模型组(13.51±2.08 比 17.18±2.42,t=4.25,P<0.05;14.02± 2.05 比 18.06±3.41,t=3.36,P<0.05;14.56±2.50 比 17.38±2.69,t=5.28,P<0.05);模型组的EGF 表达水平显著低于对照组(0.235±0.002 比 0.272±0.001,t=1.24,P<0.05;0.237±0.001 比0.268±0.002,t=2.40,P<0.05;0.240±0.003 比 0.275±0.001,t=1.20,P<0.05);复方芪参提取物组 EGF 表达水平显著高于模型组(0.252±0.001 比 0.235±0.002,t=-1.26,P<0.05;0.251± 0.003 比 0.237±0.001,t=-2.24,P<0.05;0.255±0.002 比 0.240±0.003,t=-1.40,P<0.05);模型组VEGF表达水平显著低于对照组(0.205±0.001比0.226±0.002,t=2.23,P<0.05;0.212± 0.001 比 0.239±0.002,t=1.47,P<0.05;0.217±0.001 比 0.243±0.002,t=2.26,P<0.05);复方芪参提取物组VEGF表达水平显著高于模型组(0.216±0.002比0.205±0.001,t=-2.90,P<0.05;0.225±0.002 比 0.212±0.001,t=-1.43,P<0.05;0.230±0.003 比 0.217±0.001,t=-1.63,P<0.05);模型组bFGF表达水平显著低于对照组(0.192±0.002比0.228±0.003,t=1.25,P<0.05;0.216±0.002 比 0.235±0.004,t=1.09,P<0.05;0.220±0.002 比 0.245±0.001,t=2.06,P<0.05);复方芪参提取物组bFGF表达水平显著高于模型组(0.215±0.001比0.192± 0.002,t=-1.37,P<0.05;0.228±0.001 比 0.216±0.002,t=-1.36,P<0.05;0.235±0.002 比0.220±0.002,t=-1.06,P<0.05);模型组 E-cadherin 表达水平显著低于对照组(0.286±0.002 比0.325±0.001,t=1.69,P<0.05;0.293±0.003 比 0.352±0.002,t=1.50,P<0.05;0.298±0.001比0.360±0.003,t=1.23,P<0.05);复方芪参提取物组E-cadherin水平显著高于模型组(0.301± 0.002 比 0.286±0.002,t=-1.03,P<0.05;0.314±0.003 比 0.293±0.003,t=-1.34,P<0.05;0.325±0.004比0.298±0.001,t=-1.23,P<0.05).结论 复方芪参提取物具有抗炎、促进血管再生和创面再上皮化,能够显著促进糖尿病足溃疡大鼠创面的愈合.
Mechanism of compound radix astragali extract in promoting wound healing in rats with diabetes foot ulcer
Objective To investigate the healing ability of compound astragalus extract on the wounds of diabetes foot ulcer(DFU)rats.Methods A total of 110 6-8-week old specific pathogen free(SPF)grade adult SD rats(weighing 200-250 g)were selected.Among them,36 rats were used as the control group,and the rest 74 were fed with high sugar and high fat diet and injected with low dose strepto-zotocin(STZ)to induce diabetes.A total of 72 rats with the successfully established model of DFU were randomly divided into model group and compound astragalus extract group,36 rats in each group.By drill-ing holes in the dorsal and posterior feet of rats,an ulcer wound was made.The rats in the compound Qish-en extract group received oral administration of the compound Qishen extract,and the model group and con-trol group received oral administration of physiological saline,respectively.The healing rate of ulcer wounds was observed and the enzyme linked immunosorbent assay(ELISA)was used to detect serum inter-leukin-6(IL-6)and TNF-α level.Immunohistochemistry was used to detect the expression of epidermal growth factor(EGF),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF),and E-cadherin in ulcer wound tissue.Results Compared with the control group,the wound healing rate in the model group was significantly reduced by(16.84±3.01)%vs.(43.36±4.42)%,t=8.49,P<0.05).Compared with the model group,the wound healing rate rats in the compound Qishen extract group was significantly increased[(28.50±2.62)%vs.(16.84±3.01)%,t=12.48,P<0.05].At the time points of 3,6 and 9 days,compared with the control group,the IL-6 levels in the model group were signifi-cantly increased(21.29±3.42 vs.15.78±3.06,t=-6.23,P<0.05;22.36±2.98 vs.15.69± 3.12,t=-4.26,P<0.05;22.58±3.06 vs.15.38±2.86,t=-5.45,P<0.05);Compared with the model group,the IL-6 level in the compound Qishen extract group was significantly reduced(17.99± 1.95 vs.21.29±3.42,t=4.23,P<0.05;17.95±1.87 vs.22.36±2.98,t=3.45,P<0.05;18.02±1.82 vs.22.58±3.06,t=4.62,P<0.05);Compared with the control group,the TNF-α level in the model group was significantly increased(17.18±2.42 vs.8.38±0.69,t=-8.44,P<0.05;18.06±3.41 vs.8.60±1.09,t=-7.29,P<0.05;17.38±2.69 vs.8.53±1.06,t=-6.52,P<0.05);Compared with the model group,the TNF-α level in the compound Qishen extract group was signif-icantly decreased(13.51±2.08 vs.17.18±2.42,t=4.25,P<0.05;14.02±2.05 vs.18.06±3.41,t=3.36,P<0.05;14.56±2.50 vs.17.38±2.69,t=5.28,P<0.05);Compared with the control group,the EGF expression level in the model group was significantly reduced(0.235±0.002 vs.0.272± 0.001,t=1.24,P<0.05;0.237±0.001 vs.0.268±0.002,t=2.40,P<0.05;0.240±0.003 vs.0.275±0.001,t=1.20,P<0.05);Compared with the model group,the EGF expression level in the compound Qishen extract group was significantly increased(0.252±0.001 vs.0.235±0.002,t=-1.26,P<0.05;0.251±0.003 vs.0.237±0.001,t=-2.24,P<0.05;0.255±0.002 vs.0.240±0.003,t=-1.40,P<0.05);Compared with the control group,the VEGF expression level in the model group was significantly reduced(0.205±0.001 vs.0.226±0.002,t=2.23,P<0.05;0.212±0.001 vs.0.239±0.002,t=1.47,P<0.05;0.217±0.001 vs.0.243±0.002,t=2.26,P<0.05);Compared with the model group,the VEGF expression level in the compound Qishen extract group was significantly increased(0.216±0.002 vs.0.205±0.001,t=-2.90,P<0.05;0.225± 0.002 vs.0.212±0.001,t=-1.43,P<0.05;0.230±0.003 vs.0.217±0.001,t=-1.63,P<0.05);Compared with the control group,the expression level of bFGF in the model group was significantly reduced(0.192±0.002 vs.0.228±0.003,t=1.25,P<0.05;0.216±0.002 vs.0.235±0.004,t=1.09,P<0.05;0.220±0.002 vs.0.245±0.001,t=2.06,P<0.05);ompared with the model group,the expression level of bFGF in the compound Qishen extract group was significantly increased(0.215±0.001 vs.0.192±0.002,t=-1.37,P<0.05;0.228±0.001 vs.0.216±0.002,t=-1.36,P<0.05;0.235±0.002 vs.0.220±0.002,t=-1.06,P<0.05);Compared with the con-trol group,the expression level of E-cadherin in the model group was significantly reduced(0.286±0.002 vs.0.325±0.001,t=1.69,P<0.05;0.293±0.003 vs.0.352±0.002,t=1.50,P<0.05;0.298± 0.001 vs.0.360±0.003,t=1.23,P<0.05);Compared with the model group,the E-cadherin level in the compound Qishen extract group was significantly increased(0.301±0.002 vs.0.286±0.002,t=-1.03,P<0.05;0.314±0.003 vs.0.293±0.003,t=-1.34,P<0.05;0.325±0.004 vs.0.298±0.001,t=-1.23,P<0.05).Conclusion Compound Qishen extract has anti-inflammatory effect,promotes vascular regeneration and wound re-epithelization,and can significantly promote wound healing of rats with DFU.

Diabetes footUlcerWound repairCompound Qishen extract

齐丽丽、谷丽娜、赵磊

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石家庄市中医院创面外科,石家庄 050011

糖尿病足 溃疡 创面修复 复方芪参提取物

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(5)
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