加味小陷胸中药配方颗粒对兔耳增生性瘢痕的抑制作用及其机制研究
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摘要
目的研究加味小陷胸中药配方颗粒对兔耳增生性瘢痕的抑制作用及其机制,为其临床应用提供实验依据。方法取兔建立增生性瘢痕模型,将建模成功的兔随机分为空白组、模型组、低剂量和高剂量给药组,每组4只,于手术后第21天起,给予模型组生理盐水,低、高剂量给药组相应药物,每天1次。于术后第60天取材,观察各组瘢痕组织的外观形态及病理学变化,并检测瘢痕组织中转化生长因子-β(TGF-β)、血小板衍化生长因子(PDGF-BB)、结缔组织生长因子(CTGF)、胶原蛋白Ⅰ型(CollagenⅠ)和基质金属蛋白酶-2(MMP-2)的表达水平。结果与模型组对比,低剂量给药组瘢痕指数显著降低,而高剂量给药组降低差异不明显;HE和Masson染色显示模型组瘢痕增生明显,胶原排列紊乱,呈旋满状,药物干预组胶原排列整齐,微血管数目相对较少;与空白组对比,模型组兔耳瘢痕组织中TGF-β、PDGF-BB、CTGF的含量明显升高,CollagenⅠ蛋白和mRNA的表达也显著升高,MMP-2蛋白的表达明显降低;与模型组对比,药物干预组TGF-β、CollagenⅠ蛋白的表达显著降低,MMP-2蛋白的表达明显升高。结论加味小陷胸中药配方颗粒能够抑制兔耳增生性瘢痕的形成,其作用机制可能与抑制TGF-β、PDGF-BB、CTGF的表达有关。
OBJECTIVE To study the inhibitory effects and mechanism of Jiawei Xiaoxianxiong formula granule on hypertrophic scar tissue of rabbits and to provide experimental evidence for its clinical application. METHODS The hypertrophic scar model in rabbit ears was established. The rabbits were randomly divided into 4 groups including control, model, low-dose and high-dose groups four rabbits in each group. On the 21 st day after the operation, the model group was given normal saline, and the corresponding drugs in the low-and high-dose administration groups were once a day. After 60 days, the morphological and pathological changes of the scar tissue were examined. And the levels of TGF-β, PDGF-BB, CTGF, Collagen Ⅰ and MMP-2 were detected. RESULTS Compared with the model group, hypertrophic index(HI) in low-dose group was significantly decreased, while the difference of HI in high-dose group was not significantly. HE and Masson staining showed the obvious scar hyperplasia, disordered collagenous arrangement and rotation-like appearance in the model group, while orderly collagenous arrangement and a small amount of microvessels in drug intervention groups. Compared with the control group, the contents of TGF-β, PDGF-BB and CTGF in models were increased significantly, and the expression of Collagen Ⅰprotein and mRNA were also significantly increased accompanied by significantly decreased expression of MMP-2. Compared with the model group, the expression of TGF-β and Collagen Ⅰ was significantly decreased while the expression of MMP-2 was significantly increased in drug intervention groups. CONCLUSION Jiawei Xiaoxianxiong formula granule could inhibit the formation of hypertrophic scar in rabbit ears, and its mechanism may be related to the inhibition of the expression of TGF-β, PDGF-BB and CTGF.
OBJECTIVE To study the inhibitory effects and mechanism of Jiawei Xiaoxianxiong formula granule on hypertrophic scar tissue of rabbits and to provide experimental evidence for its clinical application. METHODS The hypertrophic scar model in rabbit ears was established. The rabbits were randomly divided into 4 groups including control, model, low-dose and high-dose groups four rabbits in each group. On the 21 st day after the operation, the model group was given normal saline, and the corresponding drugs in the low-and high-dose administration groups were once a day. After 60 days, the morphological and pathological changes of the scar tissue were examined. And the levels of TGF-β, PDGF-BB, CTGF, Collagen Ⅰ and MMP-2 were detected. RESULTS Compared with the model group, hypertrophic index(HI) in low-dose group was significantly decreased, while the difference of HI in high-dose group was not significantly. HE and Masson staining showed the obvious scar hyperplasia, disordered collagenous arrangement and rotation-like appearance in the model group, while orderly collagenous arrangement and a small amount of microvessels in drug intervention groups. Compared with the control group, the contents of TGF-β, PDGF-BB and CTGF in models were increased significantly, and the expression of Collagen Ⅰprotein and mRNA were also significantly increased accompanied by significantly decreased expression of MMP-2. Compared with the model group, the expression of TGF-β and Collagen Ⅰ was significantly decreased while the expression of MMP-2 was significantly increased in drug intervention groups. CONCLUSION Jiawei Xiaoxianxiong formula granule could inhibit the formation of hypertrophic scar in rabbit ears, and its mechanism may be related to the inhibition of the expression of TGF-β, PDGF-BB and CTGF.
引文
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[10]张保国,刘庆芳.经方小陷胸汤药理学研究与临床应用[J].中成药,2012,34(11):2206-2210.
[2]SUN Y,LIAN N Q.Advance in components of traditional Chinese medicine in treatment of pathological scar[J].Chin JAesthet Med(中国美容医学杂志),2017,26(6):133-136.
[3]ZHAO J C,ZHANG B R,SHI K,et al.Lower energy radial shock wave therapy improves characteristics of hypertrophic scar in a rabbit ear model[J].Exp Ther Med,2017,15(1):933-939.
[4]CHEN F.Effect of imiquimod regulating Th1 and Th2cell-associated chemokines on wound healing and scar proliferation in rabbits[J].Chin J Aesthet Med(中国美容医学杂志),2018,27(3):101-103.
[5]NONG X L,GUO R,FENG J,et al.Research progress of natural products and compound medicines on the mechanism of skin scars inhibition[J].Nat Product Res Develop(天然产物研究与开发),2018,30(1):155-160.
[6]ZHAO J C,ZHANG B R,SHI K,et al.Lower energy radial shock wave therapy improves characteristics of hypertrophic scar in arabbit ear model[J].Exper Therapeut Med,2017,15(1):933-939.
[7]PAN S C,LEE C H,CHEN C L,et al.Angiogenin atlenuates scar formation in burn patients by reducing fibroblast proliferation and Transforming Growth Factor-β1 secretion[J].Ann plast surg,2018,80(1):S79-S83.
[8]LI Y,REN H T.Endostatin inhibits fibrosis by modulating the PDGFR/ERK signal pathway:an in vitro study[J].J Zhejiang Univ Sci B,2017,18(11):994-1001.
[9]JENSEN J,GENTZKOW G,BERMAN G,et al.Anti-CTGFoligonucleotide reduces severity of postsurgical hypertrophic scars in a randomized double-blind,within-subject,placebo-controlled study[J].Plast Reconstruct Surg,2018,142(2):192e-201e.
[10]张保国,刘庆芳.经方小陷胸汤药理学研究与临床应用[J].中成药,2012,34(11):2206-2210.