雷公藤多苷抑制二肽肽酶I活性及其调节机制的研究  

Study on inhibitory effects of Triperygium Wilfordii Polyglucoside on Dipeptidyl peptidase I and regulatory mechanism

作　　者：王晶晶[1] 蒋媛[1] 储奕[1] 柳丽[1] 周晓鹰[1] 

机构地区：[1]常州大学制药与生命科学学院,常州213164

出　　处：《中国免疫学杂志》2017年第4期537-541,共5页Chinese Journal of Immunology

基　　金：常州大学高层次人才引进启动基金(ZMF14020066);常州科技局国际交流研究基金(KYJ1520305)

摘　　要：目的:二肽肽酶I(DPPI)是一种溶酶体半胱氨酸蛋白酶,高表达于颗粒免疫细胞包括肥大细胞,有激活炎症介质丝氨酸蛋白酶的功能。本研究用胶原诱导类风湿关节炎(Collagen-induced arthritis,CIA)大鼠模型,探讨雷公藤多苷对DPPI的作用以揭示其治疗类风湿的药理机制。方法:Wistar大鼠随机分为正常组、模型组和雷公藤多苷治疗组(低剂量组2.5 mg/100 g体重,高剂量组5 mg/100 g体重);用牛Ⅱ型胶原加完全弗氏佐剂诱导大鼠类风湿关节炎,两次免疫后第12天开始灌胃给药,连续2周后处死,收集血液和滑膜。关节切片HE染色和细胞计数,荧光底物法检测DPPI在大鼠血清和滑膜中的表达和活性,明胶酶谱法检测滑膜液中MMP-2/9表达水平,BCA法测定样品总蛋白含量。结果:和模型组相比,雷公藤多苷能降低CIA大鼠关节滑膜组织中肥大细胞的数量,并抑制滑膜液和血清DPPI的活性;滑膜总蛋白和MMP-2/9活性也有所降低。结论:雷公藤多苷对DPPI活性的抑制作用可能是其治疗类风湿药理学机制之一。Objective： Dipeptidyl peptidase I （DPPI）, a lysosomal cysteine protease for serine proteases activation, highly expressed in granule immune cells. This study used collagen induced arthritis（CIA） rat model to investigate the effects of Triperygium Wilfordii Polyglucoside（TWP） on DPPI activity and the pharmacological mechanism in RA treatment. Methods ：Rats were divided into four groups randomly, the blank control group, the CIA model group, the high dose （5.0 mg/100 g body-weight） and low dose （2. 5 mg/100 g body-weight）treatment group. Bovine collagen-II plus complete Freund＇s adjuvant injected twice in rats. Physical as sessments were carried out. 12 days post-injections ,the rats of treatment group were intragastric administered with TWP every day. The rats were killed after two week administrations. Serum and synovial membrane homogenates were collected and DPPI activity was detected by fluorescence substrate. Joint HE staining and cell counting were carried out, Zymography was used to detect the MMP-2/9 activity in synovial fluids. Total protein in synovial membrane homogenates were measured by BCA method. Results：TWP could reduce the number of CIA synovial tissue mast cells, inhibited DPPI activity in the synovial fluids and in Serum. The expression levels of MMP-2/9 activity and synovium total protein content were also reduced by TWP. Conelusion：Triperygium Wilfordii Polyglucoside has inhibitory effects on DPPI activity on CIA rats,which might be the one of the oharmacologieal mechanisms in RA treatment.

关 键 词：雷公藤多苷 CIA大鼠 二肽肽酶I 类风湿关节 基质金属蛋白酶 

分 类 号：R730.5[医药卫生—肿瘤]