首页|丹参酮ⅡA对兔耳增生性瘢痕的作用效果观察及对HIF-1α信号通路的影响

丹参酮ⅡA对兔耳增生性瘢痕的作用效果观察及对HIF-1α信号通路的影响

扫码查看
目的 探索丹参酮ⅡA治疗增生性瘢痕的效果和可能机制,为瘢痕治疗的临床用药提供参考依据.方法 选取12只雄性健康白兔,共构建114个兔耳增生性瘢痕模型,随机均分为对照组、曲安奈德组和丹参酮组,每组38个瘢痕.造模后28天起,对照组注射生理盐水0.2 ml,丹参酮组注射丹参酮ⅡA磺酸钠注射液0.2 ml,曲安奈德组注射曲安奈德注射液0.2 ml,每7天注射1次,共注射4次.分别于造模后28、56天进行兔耳瘢痕量表评分、Masson染色.于造模后56天取材检测相关指标,实时荧光定量聚合酶链反应(quantitative real time-polymerase chain reaction,qPCR)检测缺氧诱导因子 1α(hypoxia inducible factor 1 alpha,HIF-1α)、转化生长因子β1(transforming growth factor beta 1,TGF-β1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)基因的相对表达量;Western blot 检测 HIF-1α、TGF-β1、VEGF蛋白表达水平.结果 术后28天时,各组兔耳瘢痕量表评分差异无统计学意义(P>0.05);术后56天时,丹参酮组与曲安奈德组兔耳瘢痕量表评分降低趋势较对照组更明显,且组间比较差异有统计学意义(P均<0.05).造模28天时各组兔耳瘢痕组织Masson染色切片在正置荧光显微镜下均可见胶原纤维蓝染,真皮上部充斥大量致密的胶原束,排列卷曲团状不规则,均符合增生性瘢痕的表现;56天时各组兔耳瘢痕组织Masson染色可见胶原纤维堆积均较28天时减少,排列更有规律;与对照组相比,丹参酮组及曲安奈德组兔耳真皮内胶原束变细,胶原束与胶原束之间具备小血管,胶原束排列更规则,部分胶原纤维排列呈现网篮状近似正常真皮内胶原排列表现.与对照组比较,丹参酮组与曲安奈德组兔耳瘢痕组织内HIF-1α、TGF-β1、VEGF基因和蛋白表达水平降低,组间比较差异均有统计学意义(P均<0.05);与曲安奈德组比较,丹参酮组兔耳瘢痕组织内HIF-1α、TGF-β1、VEGF基因和HIF-1α、VEGF蛋白表达水平降低,组间比较差异均有统计学意义(P均<0.05).结论 丹参酮ⅡA可抑制兔耳增生性瘢痕的形成,途径为通过抑制HIF-1α信号通路的激活.
Observation on the Effects of Tanshinone ⅡA on Hypertrophic Scars in Rabbit Ears and Its Impact on the HIF-1α Signaling Pathway
Objective lo explore the efficacy and possible mechanism of tanshinone ⅡA in the treatment of hyper-trophic scars,and to provide reference for clinical medication in scar treatment.Methods A total of 114 hypertrophic scar models of the rabbit ears were constructed on 12 male and healthy white rabbits,which were randomly divided into control group,triamcinolone acetonide group and tanshinone group,with 38 hypertrophic scars in each group.From 28 days after modeling,the control group was injected with 0.2 ml of saline,the tanshinone group was injected with 0.2 ml of sodium tanshinone ⅡA sulfonate injection,and the triamcinolone acetonide group was injected with 0.2 ml of triamcin-olone acetonide injection,once every 7 days for a total of 4 injections.Scar scale scores and Masson staining were per-formed on the 28th and 56th days after modeling respectively.Samples were taken 56 days after modeling to detect the re-lated indicators.The relative expression levels of hypoxia inducible factor 1 alpha(HIF-1α),transforming growth factor beta 1(TGF-β1)and vascular endothelial growth factor(VEGF)gene were detected by quantitative real time-polymerase chain reaction(qPCR),and the protein expression levels of HIF-1α,TGF-β1 and VEGF were detected by Western blot.Results At 28th day after surgery,there was no significant difference in the score of rabbit ear scar scale among all groups(P>0.05);at the 56th day after surgery,the decrease in scar scale scores in the tanshinone group and triamcinolone acetonide group was more significant than that in the control group,and the difference was statisti-cally significant(all P<0.05).At the 28th day of model-ing,Masson staining sections of each group of scar tissues showed collagen fiber blue staining under an upright fluores-cence microscope,the upper part of the dermis was filled with a large number of dense collagen bundles,arranged in a curly and irregular manner,all consistent with the appearance of hypertrophic scars;at the 56th day,Masson staining showed a decrease in collagen fiber accumulation in all groups compared to the 28th day,with a more regular arrange-ment;compared with the control group,the tanshinone group and triamcinolone acetonide group had thinner collagen bundles in the dermis,and there were small blood vessels between the collagen bundles,the arrangement of collagen bun-dles was more regular,and some collagen fibers showed a basket like arrangement similar to normal collagen arrangement in the dermis.Compared with the control group,the genes and protein expressions of HIF-1α,TGF-β1 and VEGF in scar tissues of rabbit ears decreased in the tanshinone group and the triamcinolone acetonide group,and the differences were statistically significant(all P<0.05);compared with the triamcinolone acetonide group,the HIF-1α,TGF-β1 and VEGF genes and the protein expressions of HIF-1α and VEGF in scar tissues of rabbit ears decreased in the tanshinone group,and the differences were statistically significant(all P<0.05).Conclusion Tanshinone ⅡA can inhibit the formation of hypertrophic scars in rabbit ears by inhibiting the activation of the HIF-1α signaling pathway.

Hypertrophic scarTanshinone ⅡANetwork pharmacologyHypoxia inducible factor

丁秀蓉、张洪壮

展开 >

300162 天津,武警特色医学中心急诊科

武警特色医学中心烧伤冻伤及组织功能重建研究所

陆军军医大学研究生院

增生性瘢痕 丹参酮ⅡA 网络药理学 缺氧诱导因子

2024

华南国防医学杂志
广州军区医学科学技术委员会

华南国防医学杂志

CSTPCD
影响因子:0.748
ISSN:1009-2595
年,卷(期):2024.38(3)
  • 19