槲皮素通过抑制PI3K/Akt/GLUT1信号通路治疗咪喹莫特银屑病模型小鼠的机制研究  

Study on the mechanism of quercetin in the treatment of imiquimod-induced psoriasis model mice by inhibiting the PI3K/Akt/GLUT1 signaling pathway

作　　者：马杰 吴豆豆 王菲菲 王磊[1,2] 王英 李锘[1,2] 白彦萍 MA Jie;WU Doudou;WANG Feifei;WANG Lei;WANG Ying;LI Nuo;BAI Yanping(Department of Dermatology,China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]中日友好医院皮肤科,北京100029 [2]国家中西医结合医学中心 [3]北京中医药大学中日友好临床医学院 [4]北京中医医院顺义医院皮肤科

出　　处：《环球中医药》2025年第3期444-449,共6页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81803135、81904210)。

摘　　要：目的探讨槲皮素对咪喹莫特银屑病模型小鼠糖代谢和炎症的作用及机制。方法将47只SPF雄性BALB/c小鼠随机分为空白对照组(外用凡士林)、模型组(外用咪喹莫特)、槲皮素低剂量组(30 mg/kg)、槲皮素中剂量组(60 mg/kg)、槲皮素高剂量组(120 mg/kg)和雷公藤组(7.56 mg/kg)。外用咪喹莫特乳膏62.5 mg/天,连续7天,制备咪喹莫特银屑病小鼠模型。分别给予生理盐水、低、中、高剂量槲皮素和雷公藤灌胃,并予造模第8天取材。采用免疫组织化学技术检测小鼠皮损中葡萄糖转运蛋白1(glucose transporter 1,GLUT1)蛋白的表达;蛋白免疫印迹检测小鼠皮损中丝氨酸/苏氨酸蛋白激酶B(protein kinase B,PKB/Akt)、磷酸化Akt(pAkt,即Akt呈活化状态)和GLUT1蛋白的表达水平,流式细胞仪检测小鼠血清炎症因子的含量。结果(1)免疫组化结果:建立咪喹莫特银屑病模型小鼠后,与空白对照组相比,模型组的GLUT1蛋白相对表达量显著升高(P<0.05),槲皮素中、高剂量组的GLUT1蛋白相对表达量均显著低于模型组(P<0.05)。(2)蛋白免疫印迹检测结果:与空白对照组相比,模型组的pAkt/Akt显著升高(P<0.05),槲皮素高剂量组的pAkt/Akt显著低于模型组(P<0.05)。(3)流式结果:与空白对照组相比,模型组血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-17A、IL-6、IL-10水平均显著升高,槲皮素高剂量组血清中TNF-α、IL-6和IL-17A水平均显著低于模型组(P<0.05)。结论槲皮素可能通过抑制PI3K/Akt/GLUT1信号通路发挥对咪喹莫特银屑病模型小鼠的治疗作用。Objective To investigate the effect and mechanism of quercetin on glucose metabolism and inflammation in imiquimod-induced psoriasis model mice.Methods 47 SPF female BALB/c mice were randomly divided into the blank control group(topical Vaseline),the model group(topical imiquimod),the quercetin low-dose group(30 mg/kg),the quercetin medium-dose group(30 mg/kg),the quercetin high-dose group(30 mg/kg)and the tripterygium vine group(7.56 mg/kg).Immunohistochemistry was used to detect Glucose transporter 1(GLUT1)Protein expression in mouse skin lesions.Western Blot was used to detect the expression of serine/threonine Protein Kinase B in mouse skin lesions.The expression levels of PKB/Akt,phosphorylated Akt(pAkt,Akt is activated),and GLUT1 protein were detected by the method of flow cytometry.Results(1)After the establishment of imiquimod-induced psoriasis model mice,compared with the control group,the GLUT1 protein relative expression level in the model group was significantly increased(P<0.05).GLUT1 protein relative expression level in the quercetin medium and high dose groups was significantly lower than that in the model group(P<0.05).(2)Compared with the control group,pAkt/Akt in the model group was significantly increased(P<0.05),and pAkt/Akt in the high-dose quercetin group was significantly lower than that in the model group(P<0.05).(3)Compared with the control group,the serum levels of TNF-α,IL-17A,IL-6,and IL-10 in the model group were significantly increased,and the serum levels of TNF-α,IL-6,and IL-17A in the quercetin high-dose group were significantly lower than those in the model group(all P<0.05).Conclusion Quercetin may play a therapeutic role in imiquimod-induced psoriasis model mice by inhibiting the PI3K/Akt/GLUT1 signaling pathway.

关 键 词：银屑病 清热凉血方 槲皮素 丝氨酸/苏氨酸蛋白激酶B信号通路 葡萄糖转运蛋白1蛋白 

分 类 号：R285.5[医药卫生—中药学]