土槿乙酸抑制接触性超敏反应的药效学研究及机制探讨  

Pharmacodynamic analysis and related mechanisms of pseudolaric acid B on contact hypersensitivity

作　　者：李覃[1,2] 董小青[1] 王翼腾 刘晓光[3] 王伟[4] 周欣[2,4] 陈虹[3,5] 

机构地区：[1]武警后勤学院病原生物与免疫学教研室,天津300309 [2]天津市心血管重塑与靶器官损伤重点实验室,天津300162 [3]武警后勤学院生药与药剂学教研室,天津300309 [4]武警后勤学院附属医院,天津300162 [5]天津市职业与环境危害生物标志物重点实验室,天津300309

出　　处：《中国药理学通报》2014年第11期1552-1557,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81202843);中国博士后科学基金(No 201104796;20090461498);天津市应用基础与前沿技术研究计划(No 11JCYBJC14600;14JCZDJC36700)

摘　　要：目的观察中药土槿皮主要活性成分土槿乙酸(pseudolaric acid B,PB)免疫调节作用的药效学,初步探究其可能的分子机制。方法以二硝基氟苯(2,4-dinitrofluorobenzene,DNFB)诱导小鼠接触性超敏反应(contact hypersensitivity,CHS)模型,口服不同剂量PB进行干预,检测小鼠耳肿胀度,计算脾脏指数,并以苏木精-伊红染色观察小鼠耳部皮肤炎性细胞浸润情况,综合评价PB免疫抑制作用的药效学。随后,进一步以Western blot方法检测PB对CHS小鼠Akt磷酸化活性及对PPARγ蛋白表达的影响,通过荧光素酶报告基因分析PPARγ的转录激活。结果结果显示,不同剂量PB能够明显抑制CHS小鼠耳肿胀,降低脾脏指数,减轻耳部皮肤炎症程度,其免疫抑制作用机制可能与促进PPARγ表达及其转录激活、下调Akt信号通路有关。结论 PB可能通过调节PPARγ相关的Akt信号通路发挥免疫调节作用,为研制用于炎症免疫性疾病的新型免疫调节剂奠定了基础。Aim To investigate the pharmacodynamic experiment and molecular mechanisms of a diterpenoid from cortex pseudolaricis, pseudolaric acid B （ PB ） , on immunoregulation. Methods The mouse models of contact hypersensitivity （ CHS） were induced by 2,4-dinitrofluorobenzene （ DNFB ） . Then , the ear swelling＆amp;nbsp;and spleen index were measured after administered o-rally with PB. The pathological changes such as in-flammatory cell infiltration in ear skin were observed by hematoxylin and eosin （ HE ） staining. Besides, the expression of peroxisome proliferater-activated receptorγ （ PPARγ） and the phosphorylation of Akt were ana-lyzed by Western blot. The activity of PPARγ was fur-ther detected by luciferase reporter gene assay. Results The results showed that PB could both alleviate the ear thickness, inhibit the spleen index, and reduce the inflammatory degree of their ear skin, which might be involved in inducing PPARγexpression and activation, associated with suppressing Akt signaling pathway. Conclusion It is suggested that PB might regulate PPARγ-related Akt pathway, which indicates the pos-sibility of developing PB as a novel immunoregulation agent for treating inflammatory-immune disease.

关 键 词：土槿乙酸 接触性超敏反应 药效学 炎症 PPARΓ 信号通路 PPARΓ 

分 类 号：R392.3[医药卫生—免疫学]