摘要
目的观察湖北枫杨乙醇提取物对SD大鼠CIA模型的治疗作用,并对其抗炎和促凋亡的机制进行初步探索。方法构建CIA模型后,测量其体质量、足跖肿胀率、关节炎指数;通过药物灌胃治疗后,观察各组大鼠膝关节滑膜病理形态变化,血清TNF-α、IL-1β、ALT、AST、BUN、SCr变化,膝关节滑膜内NF-κB p65磷酸化(p-p65)、cleaved caspase-3、Bcl-2、Bax表达。结果不同剂量湖北枫杨乙醇提取物组及雷公藤组使大鼠体质量增加,足跖肿胀率、关节炎指数下降(P<0.05);膝关节滑膜中炎性细胞减少,凋亡滑膜细胞增多;血清TNF-α、IL-1β降低(P<0.05);滑膜内p-p65、Bcl-2表达减少,cleaved caspase-3、Bax表达增加;湖北枫杨乙醇提取物各组ALT、AST、BUN、SCr下降(P<0.05)。结论湖北枫杨乙醇提取物对SD大鼠CIA模型有很好的治疗效果,其机制可能与调控相关炎性细胞因子TNF-α和IL-1β的表达及诱导滑膜细胞凋亡有关,同时该提取物可改善CIA大鼠肝、肾损伤。
Aim To observe the therapeutic effect of Pterocarya hupehensis Skan ethanol extract(PHSEE)on CIA model of SD rats and to explore the mechanism of anti-inflammation and pro-apoptosis.Methods After the CIA model was established,the body weight,paw swelling rate,as well as arthritis index were recorded every7days.The rats were continuously fed with PHSEE or TG for28days.The pathological changes of knee joint synovial membrane were observed in each group,while the apoptotic synoviocytes were evaluated by TUNEL assay.The changes of TNF-α,IL-1β,ALT,AST,BUN and SCr in the serum were tested by ELISA.And the expressions of NF-κB p65phosphorylation(p-p65),cleaved caspase-3,Bcl-2and Bax in the synovial tissue protein of the knee joint were detected by Western blot.Results Compared with model group,the paw swelling rate and arthritis index decreased in TG and PHSEE-treated groups with statistical significance(P<0.05).The decrease of inflammatory cells and increase of the apoptotic synovial cells were observed in the synovium of the knee from either TG and PHSEE-treated groups.The inflammatory cytokines TNF-αand IL-1βin the serum from TG and PHSEE-treated rats decreased significantly(P<0.05).The expression of apoptosis-downregulating proteins p-p65and Bcl-2in the synovium of TG and PHSEE-treated rat decreased significantly,while the expression of apoptosis-upregulating markers cleaved caspase-3and Bax increased.More interestingly,the levels of ALT,AST,BUN,and SCr in the serum of PHSEE-treated groups decreased significantly(P<0.05).However,this phenomena was not found in TG group.Conclusions PHSEE has a good therapeutic efficacy on CIA rat.The mechanism may be related to down-regulating the expression of inflammatory cytokines and inducing apoptosis of synovial cells.At the same time,the extract can improve impaired liver and kidney function in CIA rats.
作者
朱健
武璐璐
张全书
王翔鹏
袁林
向阳
ZHU Jian;WU Lu-lu;ZHANG Quan-shu;WANG Xiang-peng;YUAN Lin;XIANG Yang(Medical College of Hubei University for Nationalities, Enshi Hubei 445000,China;Hubei Provincial Key Lab of Occurrence and Intervention of Rheumatic Diseases, Enshi Hubei 445000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2019年第1期117-123,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81260458
81360672)
关键词
湖北枫杨
类风湿关节炎
CIA模型
炎症
凋亡
滑膜细胞
Pterocarya hupehensis Skan
rheumatoid arthritis
CIA model
inflammation
apoptosis
synoviocytes
