摘要
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.
Abstract
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.
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