摘要
目的:研究补骨脂素减少炎症和抑制Ras/Raf1表达保护类风湿关节炎大鼠的机制。方法:将SD大鼠分成对照组、模型组(类风湿关节炎大鼠模型)、补骨脂素低剂量组(22 mg/kg补骨脂素处理)、补骨脂素中剂量组(44 mg/kg补骨脂素处理)、补骨脂素高剂量组(88 mg/kg补骨脂素处理)、补骨脂素高剂量+NC组(88 mg/kg补骨脂素+阴性对照慢病毒载体处理)、补骨脂素高剂量+Ras组(88 mg/kg补骨脂素+Ras过表达慢病毒载体处理);采用Western Blotting检测大鼠的肾素-血管紧张素系统(RAS)、原癌基因丝苏氨酸蛋白激酶-1(Raf1)、成骨细胞特异性转录因子(Osx)、Ⅰ型胶原蛋白α1链(COL1A1)、骨钙素(OC)、基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-13(MMP-13)蛋白表达;检测关节肿胀度,HE染色对关节组织病理评分,ELISA法检测炎症介质白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平。结果:与对照组比较,模型组大鼠关节组织中Ras、Raf1、MMP-3、MMP-13蛋白表达以及关节肿胀度、关节组织病理评分和IL-2、TNF-α、IL-6水平均升高,Osx、COL1A1、OC蛋白表达均降低(均P<0.05);与模型组比较,补骨脂素低、中、高剂量组大鼠关节组织中除Osx、COL1A1、OC蛋白表达均升高外,其他指标均显著降低(均P<0.05);与补骨脂素高剂量+NC组比较,补骨脂素高剂量+Ras组大鼠关节组织中Osx、COL1A1、OC蛋白表达均降低,而其他指标均显著升高(均P<0.05)。结论:补骨脂素通过减少炎症和抑制Ras/Raf1表达减轻类风湿关节炎大鼠关节损伤,促进软骨修复。
Objective:To study the mechanism of psoralen in reducing inflammation and inhibiting the expression of Ras/Raf1 to protect rheumatoid arthritis rats.Methods:The SD rats were divided into a control group,a model group(rheumatoid arthritis rat model),a low-dose psoralen group(22 mg/kg psoralen treatment),and a middle-dose psoralen group(44 mg/kg psoralen treatment),a high-dose psoralen group(88 mg/kg psoralen treatment+negative control lentiviral vector treatment),a psoralen high-dose+Ras group(88 mg/kg psoralen+Ras overexpression lentiviral vector treatment).Western Blotting was used to detect Ras,Raf1,Osx,COL1A1,OC,MMP-3,MMP-13 protein expression,detection of joint swelling,HE staining joint histopathology score.ELISA method was used to detect IL-2,TNF-α,IL-6 level.Results:Compared with the control group,the expression of Ras,Raf1,MMP-3,and MMP-13 protein in the joint tissues of the model group increased,and the degree of joint swelling,joint histopathological score and IL-2,TNF-α,IL-6 level increased,and the protein expression of Osx,COL1A1,and OC decreased(P s<0.05);compared with the model group,the low,middle,high dose psoralen group the protein expressions of Osx,COL1A1 and OC were all increased,and other indexes were significantly decreased in the joint tissue of rats(P s<0.05);compared with the high-dose psoralen+NC group,Osx,COL1A1,and OC protein expression decreased,while other indicators were significantly increased(P s<0.05).Conclusion:Psoralen reduces inflammation and inhibits the expression of Ras/Raf1,reduces joint damage in rheumatoid arthritis rats and promotes cartilage repair.
作者
苏清君
李鹏
边朝辉
宋广明
马文明
张杰
SU Qingjun;LI Peng;BIAN Zhaohui;SONG Guangming;MA Wenming;ZHANG Jie(Joint Second Department,Wangjing Hospital,China Academy of Chinese Medical Sciences,Beijing 100102,China;Department of Orthopaedics,Fangshan Hospital,Beijing University of Chinese Medicine,Beijing 102400,China;Department of Clinical Medicine,Guangzhou Medical University,Guangzhou 511400,China)
出处
《世界中医药》
CAS
2021年第21期3180-3184,3190,共6页
World Chinese Medicine
基金
国家自然科学基金项目(82275433)
中国管理科学研究院教育科学研究所科教创新研究中心重点项目(KJCX4564)。
