羟基红花黄色素A对骨性关节炎模型大鼠炎症因子水平及Notch信号通路的影响  

Effects of hydroxysafflor yellow A on inflammatory factors levels and Notch signaling pathway in osteoarthritis model rats

作　　者：姚弘毅[1] 程凯[1] 王琳[1] 李媛媛[1] 谢钢 Yao Hongyi;Cheng Kai;Wang Lin;Li Yuanyuan;Xie Gang(Department of Rehabilitation Medicine,Liyuan Hospital Affiliated to Tongji Medical College Huazhong University of Science and Technology,Wuhan 430077,China)

机构地区：[1]华中科技大学同济医学院附属梨园医院康复医学科,武汉430077

出　　处：《中国医药》2020年第6期927-931,共5页China Medicine

基　　金：湖北省中医药科研立项项目(ZY2019F039)。

摘　　要：目的探讨羟基红花黄色素A(HSYA)对骨性关节炎(OA)模型大鼠血清及滑膜中炎症因子水平及Notch信号通路的影响。方法选取60只无特定病原体级雄性大鼠,按照随机数字表法分为空白对照组、模型对照组和HSYA 2.5、5、10 mg/kg组,每组12只。采用Mankin's评分与关节炎指数(AI)评分评估造模是否成功。收集血清并分离关节滑膜,检测膝关节活动度、关节滑膜肿胀厚度及软骨含水率。采用酶联免疫吸附法检测血清及滑膜中肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、γ干扰素、IL-6、IL-17水平。实时荧光定量聚合酶链反应检测软骨组织Notch1 mRNA表达量。蛋白质印迹法检测软骨组织Notch信号通路相关蛋白Notch1、Hes1、Hes5、Jagged1的表达。结果与空白对照组比较,模型对照组大鼠软骨组织Mankin's评分及AI评分均明显增加[(8.16±0.59)分比(1.03±0.08)分、(5.12±1.32)分比0分],膝关节活动度明显缩窄[(102±10)°比(157±7)°],关节滑膜肿胀厚度和关节软骨含水率明显增加[(0.41±0.06)mm比(0.23±0.08)mm、(45.2±2.2)%比(36.8±3.1)%](均P<0.05);与模型对照组比较,HSYA 2.5、5、10 mg/kg组大鼠软骨组织Mankin's评分及AI评分均明显减少,膝关节活动度明显扩大,关节滑膜肿胀厚度和关节软骨含水率均明显降低(均P<0.05)。与空白对照组比较,模型对照组大鼠血清及滑膜中TNF-α、IL-1β、γ干扰素、IL-6、IL-17含量,关节软骨组织中Notch1 mRNA及Notch1、Hes1、Hes5、Jagged1蛋白表达水平均明显升高(均P<0.05);与模型对照组比较,HSYA 2.5、5、10 mg/kg组大鼠血清及滑膜中TNF-α、IL-1β、γ干扰素、IL-6、IL-17含量,关节软骨组织中Notch1 mRNA及Notch1、Hes1、Hes5、Jagged1蛋白表达水平均明显降低(均P<0.05)。结论HSYA能够明显降低OA大鼠体内炎症因子含量而减轻软骨损伤,这种作用可能是通过抑制Notch信号通路实现的。Objective To investigate the effects of hydroxysafflor yellow A(HSYA)on inflammatory factor levels and Notch signaling pathway in serum and synovium of osteoarthritis(OA)model rats.Methods Sixty healthy rats were randomly divided into a blank control group,a model group(OA model rat),HSYA 2.5 mg/kg group,HSYA 5 mg/kg group and HSYA 10 mg/kg group.There were 12 rats in each group.Mankin's score and arthritis index(AI)were used to assess the success of the model.After the rats were sacrificed,serum was collected and the synovial membrane was separated;the knee joint activity,joint synovial thickness and cartilage water content were measured.The levels of tumor necrosis factor(TNF-α),interleukin 1β(IL-1β),IL-6,interferonγ(IFN-γ)and IL-17 in serum and synovium were detected by enzyme-linked immunosorbent assay(ELISA).Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of Notch1 mRNA in cartilage tissue.Western blot was used to detect the expression of Notch signaling pathway-related proteins Notch1,Hes1,Hes5 and Jagged1 in cartilage.Results The Mankin's score and ar-thritis index(AI)of the cartilage tissue of the model group OA rats were significantly higher[(8.16±0.59)vs(1.03±0.08),(5.12±1.32)vs 0];the range of motion of the knee joint was significantly narrower[(102±10)°vs(157±7)°];the thickness of joint synovial swelling was significantly higher[(0.41±0.06)mm vs(0.23±0.08)mm];the water content of articular cartilage was higher than those of blank control group[(45.2±2.2)%vs(36.8±3.1)%](all P<0.05).The Mankin's score and AI score of cartilage tissue of HSYA rats in different dose groups were significantly lower;the range of motion of knee joint were significantly higher;the thickness of joint synovial swelling were significantly lower;the water content of articular cartilage were significantly lower than those of the model group(all P<0.05).The levels of TNF-α,IL-1β,IFN-γ,IL-6 and IL-17 in the serum and synovium and the expression levels of Notch1 mRNA and N

关 键 词：骨性关节炎 羟基红花黄色素A NOTCH信号通路 炎症因子 

分 类 号：R684.3[医药卫生—骨科学]