Protective effects of Dioscin on TNF-α-induced collagen-induced arthritis rat fibroblast-like synoviocytes involves in regulating the LTB4/BLT pathway  

作　　者：ZHIPING WEI YAJUN LIU MEIWEN YANG MENGDI LI KEXIN LI LUXI ZHENG HUIQIONG GUO FENFANG HONG SHULONG YANG 

机构地区：[1]Department of Physiology,College of Medicine,Nanchang University,Nanchang,330006,China [2]Henan Vocational College of Nursing,Anyan,455000,China [3]Nanchang University Hospital,Nanchang,330031,China [4]Department of Experimental Teaching Center,Nanchang University,Nanchang,330031,China

出　　处：《BIOCELL》2021年第4期1005-1012,共8页生物细胞（英文）

基　　金：supported by the National Natural Science Foundation of China(Nos.82060661,81660751,81660151);Jiangxi Provincial Natural Science Foundation of China(No.20171BAB205085).

摘　　要：Background and Objective:LTB4 has been shown to be involved in rheumatoid arthritis(RA)pathogenesis.The effect of Dioscin(Dio)on the LTB4 pathway of RA have not been reported yet.This study aimed at further exploring whether Dioscin’s effects on TNF-αinduced collagen-induced arthritis(CIA)rat fibroblast-like synoviocytes(FLS)connected with the LTB4 and its receptor pathway.Materials&Methods:In this experiment,control group,TNF-αgroup,and different concentrations of Dioscin groups were established.Cell viability was evaluated using MTT assay.The levels of LTB4 in the samples of above groups were measured using ELISA.The mRNA expression levels of LTA4H,BLT1,and BLT2 were detected by quantitative real time PCR,while the expression level of LTA4H proteins were detected using western blot.The distribution of LTA4H was assessed by immunofluorescence assay.Results:the LTB4 level of TNF-αgroup in sample supernatant was higher than both control group and Dioscin groups with decreased LTB4 levels(p<0.05).Compared with the control group,the expression of LTA4H was significantly increased in TNF-αgroup(p<0.05),whereas LTA4H expressions were significantly decreased in all Dioscin groups when compared to TNF-αgroup(p<0.05).The mRNA expressions of BLT1 and BLT2 were markedly higher in TNF-αgroup than those in control group while Dioscin treatment significantly inhibited the increased expressions of BLT1 and BLT2 induced by TNF-α(p<0.05).Conclusions:These results firstly demonstrate that the protective effect of Dioscin on TNF-αinduced FLS may involve in its reducing LTB4 production by down-regulating LTA4H expression,and may inhibit its downstream pathway by decreasing LTB4 receptors levels.This findings suggest that dioscin produces a potential therapeutic effects for RA via its influencing LTA4H/LTB4/BLT pathway.

关 键 词：Rheumatoid arthritis DIOSCIN Fibroblast-like synoviocytes Leukotriene B4 LTA4 hydrolase Leukotriene B4 receptor 

分 类 号：R56[医药卫生—呼吸系统]