摘要
目的 DZ2002是可逆型S-腺苷同型半胱氨酸水解酶抑制剂,该研究旨在探索DZ2002软膏对豚鼠银屑病样皮损的治疗作用及机制。方法以50 g·L-1盐酸普萘洛尔搽剂建立豚鼠银屑病模型,通过HE染色观察耳部皮肤病理改变、评估Baker总分和测量表皮厚度,并以免疫组化标记皮肤中性粒细胞的浸润。以DZ2002干预TNF-α/IFN-γ诱导活化后的HaCaT角质细胞,采用RT-PCR检测HaCaT细胞的趋化因子表达水平,采用ELISA法及Luminex多因子检测趋化因子分泌水平,以趋化试验检测该条件下的细胞上清对THP1和Jurkat细胞的趋化作用。结果模型豚鼠皮肤出现棘层肥厚、炎性细胞浸润、Munro微脓肿、角化过度、角化不全等病理表现,且皮肤Baker评分及表皮厚度均明显升高。与模型组相比,DZ2002软膏不仅明显改善豚鼠耳部皮肤的病理表现,而且降低皮肤的Baker评分及表皮厚度。DZ2002能明显下调TNF-α/IFN-γ诱导活化后的HaC aT细胞表达趋化因子IL-8和CXCL9,抑制THP1及Jurkat细胞的趋化运动。结论 DZ2002软膏通过抑制角质细胞分泌趋化因子和减少炎性细胞的浸润,发挥治疗银屑病的作用。
Aim To explore the therapeutic effect of DZ2002,a reversible S-adenosyl-L-homocysteine hydrolase inhibitor,on psoriasis-like skin lesions of guinea pig and its mechanism.Methods The guinea pig model of psoriasis was established with 50 g·L^-1 propranolol hydrochloride liniment.The pathological changes of the skin were determined by hematoxylin and eosin(HE).Then the Baker score and epidermal thickness were measured based on HE.The infiltration of neutrophils was marked by immunohistochemical staining.The expression of chemokines in TNF-α/IFN-γ-treated HaCa T cells in the present of DZ2002 or not were determined by real-time polymerase chain reaction(RT-PCR),and the production of chemokines from HaCa T cells were quantified by ELISA and Luminex x-MAP technology.In the same condition,supernatants were used to test the chemotaxis effect on Jurkat and THP1 cells via chemotaxis assays.Results Pathological features such as acanthosis,inflammatory cell infiltration,Munro microabscess,hyperkeratosis and parakeratasis appeared in the psoriasis-like skin lesions of guinea pigs.The Baker score and epidermal thickness of psoriasis-like guinea pig ear both increased significantly.Compared with vehicle group,DZ2002 cream not only significantly improved the pathological manifestations of guinea pig ear skin,but also reduced the skin Baker score and epidermal thickness.DZ2002 significantly down-regulated the expression of chemokines including IL-8 and CXCL9 in TNF-α/IFN-γ-treated HaCaT cells,and inhibited the chemotaxis of THP1 and Jurkat cells.Conclusions DZ2002 cream can significantly improve the psoriasis symptoms in guinea pig model of psoriasis via inhibiting the secretion of chemokines by keratinocytes and reducing the infiltration of inflammatory cells.
作者
李迁
祁青
杨晓倩
杨芳明
林泽民
陈付学
唐炜
左建平
LI Qian;QI Qing;YANG Xiao-qian;YANG Fang-ming;LIN Ze-min;CHEN Fu-xue;TANG Wei;ZUO Jian-ping(College of Life Science, Shanghai University, Shanghai 200444, China;Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;Science and Technology Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第4期501-507,共7页
Chinese Pharmacological Bulletin
基金
中国科学院战略性先导科技专项(No XDA12020113)
国家科技重大专项项目(No 2018X09711002-014-001)
国家自然科学基金资助项目(No 81273525)。
