紫花牡荆素对浅Ⅱ度烧伤大鼠创面愈合的影响及机制研究-中国药房

紫花牡荆素对浅Ⅱ度烧伤大鼠创面愈合的影响及机制研究

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篇名：	紫花牡荆素对浅Ⅱ度烧伤大鼠创面愈合的影响及机制研究
TITLE：	Effect and mechanism of casticin on wound healing in rats with superficial second-degree burn
摘要：	目的基于磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路探究紫花牡荆素（CAS）促进大鼠浅Ⅱ度烧伤创面愈合的作用机制。方法将大鼠随机分为对照组（生理盐水），模型组（5%羧甲基纤维素钠空白基质），CAS低、高剂量组（15mL浓度为30、60mmol/L的CAS药液），CAS高剂量+LY294002组[15mLCAS药液（60mmol/L）和PI3K抑制剂LY294002溶液（20μmmol/L）的混合溶液]和阳性对照组（厚涂京万红软膏0.5～1.0cm），每组15只。除对照组外，其余各组均通过点燃皮肤表面混合烧伤燃料来构建浅Ⅱ度烧伤大鼠模型，并于烧伤后2h内涂抹给药。给药28d后，计算大鼠烧伤创面愈合率，观察大鼠烧伤创面中央组织病理变化，检测大鼠血清中肿瘤坏死因子α（TNF-α）、白细胞介素1β（IL-1β）、IL-6和基质金属蛋白酶2（MMP-2）、MMP-9、血管内皮生长因子（VEGF）水平，检测大鼠烧伤组织中PI3K/AKT/mTOR信号通路相关蛋白的磷酸化水平。结果与对照组比较，模型组大鼠皮肤组织表皮层和真皮浅层损伤、愈合状态较差，存在炎症细胞浸润且组织结构不完整等情况；血清中IL-6、IL-1β、TNF-α、MMP-2、MMP-9水平均显著升高（P＜0.05），血清中VEGF水平和烧伤创面中央组织中PI3K、AKT、mTOR蛋白的磷酸化水平均显著降低（P＜0.05）；与模型组比较，CAS低、高剂量组大鼠上述病理变化及血清和烧伤创面中央组织中上述指标水平均显著逆转（P＜0.05），且CAS高剂量组上述指标的变化较CAS低剂量组更明显（P＜0.05）；PI3K抑制剂LY294002的加入可逆转CAS对大鼠浅Ⅱ度烧伤创面愈合的促进作用（P＜0.05）。结论CAS可促进大鼠浅Ⅱ度烧伤创面的愈合，其作用机制可能与激活PI3K/AKT/mTOR信号通路有关。
ABSTRACT：	OBJECTIVE To explore the mechanism by which casticin （CAS） promotes wound healing in superficial second- degree burned rats through phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. METHODS Rats were randomly assigned to a control group （physiological saline）， a model group （5% sodium carboxymethyl cellulose blank matrix）， low- and high-dose CAS groups （15 mL of CAS solution at concentrations of 30 and 60 mmol/L， respectively）， a high dose CAS plus LY294002 group [a mixture of 15 mL CAS solution （60 mmol/L） and PI3K inhibitor LY294002 solution （20 μmmol/L）]， and a positive control group （thick application of Jingwanhong ointment 0.5-1.0 cm）， with 15 rats in each group. Except for the control group， the other groups were subjected to a superficial second-degree burn rat model by igniting a mixture of burn fuel on the skin surface， and the administration was applied topically within two hours after the burn. After 28 days of administration， the wound healing rate of the burned rats was calculated， the histopathological changes in the central tissue of the rat’s burned wound were observed， and the levels of tumor necrosis factor α （TNF-α）， interleukin-1β （IL- 1β）， IL-6， matrix metalloproteinase-2 （MMP-2）， MMP-9 and vascular endothelial growth factor （VEGF） in the serum of rat were detected. The phosphorylation levels of related proteins in the PI3K/AKT/mTOR signaling pathway in the burned tissue of the rats were also detected. RESULTS Compared with the control group， the rats in the model group showed epidermal and superficial dermal damage in skin tissue， poor healing status， inflammatory cell infiltration， and incomplete tissue structure. The levels of IL-6， IL-1β， TNF-α， MMP-2 and MMP-9 in the serum were significantly increased （P＜0.05）， and the levels of VEGF in the serum and the phosphorylation levels of E-mail：caodongsheng@ahmu.edu.cn PI3K， AKT， mTOR proteins in the central tissue of the burned wound were significantly decreased （P＜0.05）. Compared with the model group， the pathological changes and the levels of the above indicators in the serum and central tissue of the burned wound in the CAS low- and high-dose groups were significantly reversed （P＜0.05）， and the changes in the CAS high-dose group were significantly more pronounced than those in the CAS low- dose group （P＜0.05）. The addition of the PI3K inhibitor LY294002 could reverse the promoting effect of CAS on the wound healing of superficial second-degree burned rats （P＜0.05）. CONCLUSIONS CAS can promote the healing of superficial second- degree burned wounds in rats， and its mechanism of action may be related to the activation of the PI3K/AKT/mTOR signaling pathway.
期刊：	2024年第35卷第21期
作者：	张国辉；张海博；曹东升
AUTHORS：	ZHANG Guohui，ZHANG Haibo，CAO Dongsheng
关键字：	紫花牡荆素；浅Ⅱ度烧伤；创面愈合；PI3K/AKT/mTOR信号通路
KEYWORDS：	casticin； superficial second-degree burn； wound healing； PI3K/AKT/mTOR signaling pathway
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