摘要
目的:探究小檗碱(BR)调节缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对皮肤溃疡大鼠血管生成和创面愈合的影响。方法:取SD大鼠采用创面局部多次涂抹冰醋酸建立皮肤溃疡模型,随机数字法分组,包括模型组(M组)、小檗碱低剂量组(BR-L组)、小檗碱高剂量组(BR-H组)、小檗碱高剂量+空载组(BR-H+pc-DNA组)、小檗碱高剂量+HIF-1α敲低组(BR-H+pc-HIF-1αKD组),每组10只,另选10只SD大鼠作为对照组(C组)。以药物分组处理3周后,测定各组大鼠创面愈合率;HE染色检测各组大鼠皮肤溃疡创面组织病理形态;免疫组织化学染色检测各组大鼠皮肤溃疡创面组织微血管密度(MVD)及胶原蛋白Ⅰ(CollagenⅠ)与纤维结合蛋白(FN)表达;酶联免疫吸附测定(ELISA)各组大鼠血清及皮肤溃疡创面组织炎性因子IL-6、IL-8表达水平;免疫印迹法检测各组大鼠皮肤溃疡创面组织HIF-1α/VEGF通路蛋白表达水平。结果:与C组相比,M组大鼠创面组织MVD、血清及创面组织IL-6、IL-8水平升高(均P<0.05)。与M组相比,BR-L组、BR-H组、BR-H+pc-DNA组大鼠创面愈合率、创面组织MVD、HIF-1α及VEGF蛋白表达均升高(均P<0.05),血清及创面组织IL-6、IL-8水平均降低(均P<0.05),且高剂量小檗碱作用更强。敲低HIF-1α可减弱BR对模型组大鼠各指标的作用。结论:小檗碱可通过上调HIF-1α/VEGF通路而降低炎性因子表达,抑制炎症,增强皮肤溃疡大鼠血管生成和胶原形成,促进其创面愈合。
Objective:To investigate the impacts of berberine(BR)on angiogenesis and wound healing in skin ulcer rats by regulating HIF-1α/VEGF signaling pathway.Methods:SD rat skin ulcer model was established by smearing glacial acetic acid multiple times on the wound surface,and SD rats were randomly divided into model group(M group),low-dose berberine group(BR-L group),high-dose berberine group(BR-H group),high-dose berberine+no load group group(BR-H+pc-DNA group),high-dose berberine+HIF-1αknockdown group(BR-H+pc-HIF-1αKD group),with 10 rats in each group,another 10 SD rats were selected as the control group(C group).After 3 weeks of treatment with drugs,the healing rate of skin ulcer wound of rats in each group was determined;HE staining was used to detect the pathological morphology of skin ulcer wound of rats in each group;the microvessel density(MVD)and the expression of collagenⅠand fibronectin(FN)of skin ulcer wound of rats in each group were detected by immunohistochemistry;the levels of IL-6 and IL-8 in serum and skin ulcer wound tissue of rats in each group were detected by ELISA;the expressions of HIF-1α/VEGF pathway protein in skin ulcer wound tissue of rats in each group were detected by Western blot.Results:Compared with the C group,the positive expression of MVD of wound tissue,the levels of IL-6 and IL-8 in serum and wound tissue in the M group increased(all P<0.05).Compared with the M group,the healing rate of wound,the positive expression of MVD,the expression of HIF-1αand VEGF proteins in the wound tissue in the BR-L group,the BR-H group,and the BR-H+pc-DNA group increased(all P<0.05),the levels of IL-6 and IL-8 in serum and wound tissue decreased(all P<0.05),high-dose berberine has a stronger effect.Knock down HIF-1αcould weaken the effect of BR on various indicators of model group rats.Conclusion:Berberine can reduce the expression of inflammatory factors,inhibit inflammation,enhance angiogenesis and collagen formation,and promote wound healing of skin ulcer rats by up-regulating HIF-1α/VEGF signaling pathway.
作者
齐淑静
付改霞
齐瑞霞
QI Shujing;FU Gaixia;QI Ruixia(Affiliated Hospital of Hebei Engineering University,Handan 056001,China)
出处
《陕西医学杂志》
CAS
2024年第2期173-178,共6页
Shaanxi Medical Journal
基金
河北省医学科学研究计划项目(20210009)。
