天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (11): 1045-1049.doi: 10.11958/20200457

• 实验研究 • 上一篇    下一篇

凉血消银颗粒剂对银屑病转基因小鼠模型miR-155/SOCS1轴的影响

段紫钰，李建国，陈静，刘鸿伟，李丽娜，周武，张守民△   

  1. 河南省人民医院皮肤科、郑州大学人民医院、河南大学临床医学院（邮编450003）
  • 收稿日期:2020-03-13 修回日期:2020-08-13 出版日期:2020-11-15 发布日期:2020-11-15

The effect of Liangxue Xiaoyin granule on miR-155/SOCS1 axis in psoriasis transgenic mouse model

DUAN Zi-yu, LI Jian-guo, CHEN Jing, LIU Hong-wei, LI Li-na, ZHOU Wu, ZHANG Shou-min△   

  1. Department of Dermatology, Henan People's Hospital, People's Hospital of Zhengzhou University, Clinical Medical College of Henan University, Zhengzhou 450003, China
  • Received:2020-03-13 Revised:2020-08-13 Published:2020-11-15 Online:2020-11-15

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摘要： 目的　研究凉血消银颗粒剂对银屑病模型（K14-VEGF转基因）小鼠的治疗效果及对微小RNA-155（miR-155）/细胞因子信号转导抑制因子1（SOCS1）轴的影响。方法　未经任何处理的远交系Swiss小鼠（FVB/NJ）8只作为对照组；另将经K14-VEGF转基因小鼠（SPF级）24只按随机数字表法分为模型组、凉血消银颗粒剂组及甲氨蝶呤组，每组8只。凉血消银颗粒剂以60 g/kg剂量灌胃，甲氨蝶呤组以2 mg/kg剂量灌胃，每日均灌胃1次，对照组和模型组灌胃生理盐水；连续给药10 d后处死，观察各组小鼠银屑病皮损严重程度指数（PASI）评分；HE染色观察细胞形态学变化；酶联免疫吸附测定（ELISA）法检测小鼠血清中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-23、IL-6、IL-1表达水平；实时荧光定量逆转录聚合酶链反应（qPCR）检测miR-155表达水平；蛋白质印迹法测定SOCS1蛋白表达水平。结果　与对照组相比，模型组表现为棘层增厚、真皮浅层淋巴细胞浸润等；与模型组比较，凉血消银颗粒剂组、甲氨蝶呤组小鼠病理严重程度显著降低，细胞形态恢复。与对照组相比，模型组PASI评分、TNF-α、IL-23、IL-6、IL-1、miR-155表达水平显著升高（P＜0.05），SOCS1表达水平显著降低（P＜0.05）；与模型组相比，凉血消银颗粒剂组、甲氨蝶呤组PASI评分、TNF-α、IL-23、IL-6、IL-1、miR-155表达水平显著降低（P＜0.05），SOCS1表达水平显著升高（P＜0.05）；凉血消银颗粒剂组与甲氨蝶呤组上述指标相比差异无统计学意义（P＞0.05）。结论　凉血消银颗粒剂可能通过抑制miR-155/SOCS1轴活化，减轻炎症反应。

关键词: 银屑病, 微RNAs, 细胞因子信号转导抑制因子1, 肿瘤坏死因子α, 白细胞介素类, 凉血消银颗粒剂, 微小RNA-155

Abstract: Objective To study the therapeutic effect of Liangxue Xiaoyin granule on psoriasis transgenic mice (K14-VEGF) and its effect on the miR-155/cytokine signal transduction inhibitor 1 (SOCS1) axis. Methods　Eight untreated Swiss outbred line (FVB/NJ) mice were randomly selected as the control group. In addition, 24 SPF K14-VEGF transgenic mice were according to random number table method divided into model group, Liangxue Xiaoyin granule group and methotrexate group, 8 in each group. The control group and model group were intragastrically administered normal saline, Liangxue Xiaoyin granule group was intragastrically administered at a dose of 60 g/kg, methotrexate group was intragastrically administered at a dose of 2 mg/kg, once a day for 10 days. The severity index (PASI) score of psoriasis was observed, and the morphological changes of cells were observed by HE staining. The expression levels of serum TNF-α, IL-23, IL-6 and IL-1 were detected by enzyme-linked immunosorbent assay (ELISA). The real-time fluorescence quantitative analysis (qPCR) was used to detect the expression of miR-155, and the expression of SOCS1 protein was determined by Western blot (WB) assay. Results　Compared with the control group, the model group showed spinous layer thickening and superficial dermal lymphocyte infiltration. Compared with the model group, the pathological severity of mice decreased significantly, and the cell morphology recovered in the Liangxue Xiaoyin granule group and the methotrexate group. Compared with the control group, the PASI score, the expression levels of TNF-α, IL-23, IL-6, IL-1 and miR-155 were significantly higher, the expression level of SOCS1 was decreased significantly in the model group (P < 0.05). Compared with model group, the PASI score, the expression levels of TNF-α, IL-23, IL-6, IL-1 and miR-155 were decreased significantly in Liangxue Xiaoyin granule group and methotrexate group (P < 0.05), and the expression level of SOCS1 was significantly higher (P < 0.05). There was no significant difference between Liangxue Xiaoyin granule group and methotrexate group (P＞0.05). Conclusion　Liangxue Xiaoyin granule may alleviate the inflammatory reaction and alleviate the symptoms of psoriasis transgenic mice by inhibiting the activation of the miR-155/SOCS1 axis.

Key words: psoriasis, microRNAs, suppressor of cytokine signaling 1 protein, tumor necrosis factor-alpha, interleukins, Liangxue Xiaoyin granule, miR-155