摘要
目的探究高良姜素(Gal)对银屑病大鼠皮肤损伤及磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的影响。方法将60只大鼠随机分为6组,即对照组、咪喹莫特乳膏(IMQ)组、Gal低、中、高剂量组和740Y-P组,每组10只。除对照组外,其余5组采用IMQ构建银屑病大鼠模型。造模成功后,Gal低、中、高剂量组大鼠分别在皮损处涂抹0.5%、1%、2%的Gal乳膏,740Y-P组大鼠在皮损处涂抹2%Gal乳膏+740Y-P 10 mg/kg腹腔注射,对照组和IMQ组同时予等量凡士林外涂+0.9%氯化钠注射液静脉注射。比较各组大鼠银屑病面积和严重程度指数(PASI)、脾脏指数、背部皮损组织病理学评分,血清肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-17、IL-22水平,微管相关蛋白轻链3-B(LC3-B)表达,自噬及PI3K/Akt/mTOR信号通路蛋白表达。结果与对照组相比,IMQ组大鼠背部皮肤表皮增厚,出现红斑和严重角化病,炎症细胞浸润,PASI评分、脾脏指数、背部皮损组织病理评分、TNF-α、IL-17、IL-22、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR、p62表达均升高,B细胞淋巴瘤(Bcl-2)同源结构域蛋白抗体-1(Beclin-1)、LC3-B表达降低(均P<0.05);与IMQ组相比,Gal低、中、高剂量组皮肤损伤程度和病理学变化减轻,PASI评分、脾脏指数、背部皮损组织病理评分、TNF-α、IL-17、IL-22、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR、p62表达均降低,Beclin-1、LC3-B表达升高(均P<0.05);与Gal高剂量组相比,740Y-P组大鼠皮肤损伤加重,PASI评分、脾脏指数、背部皮损组织病理评分、TNF-α、IL-17、IL-22、p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR、p62表达均升高,Beclin-1、LC3-B表达均降低(均P<0.05)。结论Gal能够减轻银屑病大鼠皮肤损伤,抑制炎症反应,促进自噬,作用机制可能与抑制PI3K/Akt/mTOR信号通路有关。
Objective To investigate the effect of galangin(GAL)on skin damage in psoriasis rats and analyze its relationship with the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods Sixty rats were equally randomly separated into a control group(external application of Vaseline+intrathecal injection of 0.9%sodium chloride,qd),imiquimod(IMQ,external application of Vaseline+intrathecal injection of 0.9%sodium chloride,qd)group,low,medium,and high-dose GAL groups(respective 0.5%,1%and 2%Gal cream at the skin lesions,qb),and 740Y-P(activator)group(high-dose GAL plus 740Y-P,10 mg/kg,qb),10 per group.A psoriasis rat model was constructed using imiquimod cream except for the control group.After successful modeling,the rats in each group were evaluated for Psoriasis Area and Severity Index(PASI)and measured for Spleen Index.The serum levels of tumor necrosis factor-α(TNF-α),interleukin-17(IL-17),and IL-22 and the expression of light chain 3B(LC3-B),cell autophagy,the expression proteins of PI3K/Akt/mTOR signaling pathway were detected.Results Compared with the control group,the rats of the IMQ group showed thickened the skin epidermis on the back,with erythema and severe keratosis,and infiltration of inflammatory cells;the PASI score,spleen index,histopathological score,the expression of TNF-α,IL-17,IL-22,p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,and p62 were significantly increased,the expression of Beclin-1 and LC3-B were significantly decreased(P<0.05).Compared to the IMQ group,the degree of skin damage and pathological changes were significantly reduced in the low,medium,and high-dose GAL groups,the PASI score,spleen index,histopathological score,the expression of TNF-α,IL-17,IL-22,p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,and p62 were significantly decreased,the expression of Beclin-1 and LC3-B were significantly increased(P<0.05).Compared to the high-dose GAL group,the skin damage of rats in the 740Y-P group worsened,the PASI score,spleen index,histopathological score,the expression of TNF-α,IL-17,IL-22,p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,and p62 were significantly increased,the expression of Beclin-1 and LC3-B were significantly decreased(P<0.05).Conclusion GAL can alleviate skin damage in psoriasis rats,inhibit inflammatory response,promote autophagy by the inhibition of the PI3K/Akt/mTOR signaling pathway.
作者
薛雯
聂堂政
狄伟
XUE Wen;NIE Tangzheng;DI Wei(Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550000;The First Clinical Medical College,Heilongjiang University of Chinese Medicine,Harbin 150006;Department of Dermatology,the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550001)
出处
《河北中医》
2025年第6期970-975,981,共7页
Hebei Journal of Traditional Chinese Medicine
基金
贵州省中医药管理局中医药、民族医药科学技术研究课题(编号:QZYY-2021-099)。
