中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2014年
11期
1552-1556,1557
,共6页
李覃%董小青%王翼腾%刘晓光%王伟%周欣%陈虹
李覃%董小青%王翼騰%劉曉光%王偉%週訢%陳虹
리담%동소청%왕익등%류효광%왕위%주흔%진홍
土槿乙酸%接触性超敏反应%药效学%炎症%PPARγ%Akt%信号通路
土槿乙痠%接觸性超敏反應%藥效學%炎癥%PPARγ%Akt%信號通路
토근을산%접촉성초민반응%약효학%염증%PPARγ%Akt%신호통로
pseudolaric acid B%contact hypersensitiv-ity%pharmacodynamics%inflammation%PPARγ%Akt%signaling pathway
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-dinitrofluoro-benzene,DNFB)诱导小鼠接触性超敏反应( contact hypersen-sitivity,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。
目的:觀察中藥土槿皮主要活性成分土槿乙痠(pseudolaric acid B,PB)免疫調節作用的藥效學,初步探究其可能的分子機製。方法以二硝基氟苯(2,4-dinitrofluoro-benzene,DNFB)誘導小鼠接觸性超敏反應( contact hypersen-sitivity,CHS)模型,口服不同劑量PB進行榦預,檢測小鼠耳腫脹度,計算脾髒指數,併以囌木精-伊紅染色觀察小鼠耳部皮膚炎性細胞浸潤情況,綜閤評價PB免疫抑製作用的藥效學。隨後,進一步以Western blot方法檢測PB對CHS小鼠Akt燐痠化活性及對PPARγ蛋白錶達的影響,通過熒光素酶報告基因分析PPARγ的轉錄激活。結果結果顯示,不同劑量PB能夠明顯抑製 CHS小鼠耳腫脹,降低脾髒指數,減輕耳部皮膚炎癥程度,其免疫抑製作用機製可能與促進PPARγ錶達及其轉錄激活、下調Akt信號通路有關。結論 PB可能通過調節PPARγ相關的Akt信號通路髮揮免疫調節作用,為研製用于炎癥免疫性疾病的新型免疫調節劑奠定瞭基礎。
목적:관찰중약토근피주요활성성분토근을산(pseudolaric acid B,PB)면역조절작용적약효학,초보탐구기가능적분자궤제。방법이이초기불분(2,4-dinitrofluoro-benzene,DNFB)유도소서접촉성초민반응( contact hypersen-sitivity,CHS)모형,구복불동제량PB진행간예,검측소서이종창도,계산비장지수,병이소목정-이홍염색관찰소서이부피부염성세포침윤정황,종합평개PB면역억제작용적약효학。수후,진일보이Western blot방법검측PB대CHS소서Akt린산화활성급대PPARγ단백표체적영향,통과형광소매보고기인분석PPARγ적전록격활。결과결과현시,불동제량PB능구명현억제 CHS소서이종창,강저비장지수,감경이부피부염증정도,기면역억제작용궤제가능여촉진PPARγ표체급기전록격활、하조Akt신호통로유관。결론 PB가능통과조절PPARγ상관적Akt신호통로발휘면역조절작용,위연제용우염증면역성질병적신형면역조절제전정료기출。
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 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.