2019 年第 4 期 第 14 卷

蒙药森登-4汤抑制胶原诱导性关节炎大鼠骨破坏作用机制及对滑膜成纤维细胞体外增殖的影响

Inhibitory effect of Mongolian medicine Sendeng-4 decoction on bone destruction in rats with collagen-induced arthritis and the effect on synovial fibroblasts in vitro culture

作者：那仁满都拉卢计平姜清秀郭彦

英文作者：

单位：010017呼和浩特，内蒙古自治区人民医院蒙医科（那仁满都拉），药剂处（卢计平），病理科（郭彦）；010010呼和浩特，内蒙古医科大学蒙医药学院（姜清秀）

英文单位：

关键词：胶原诱导性关节炎大鼠；蒙药森登-4汤；骨破坏；滑膜成纤维细胞

英文关键词：

• 摘要：

• 【摘要】目的    研究蒙药森登-4汤抑制胶原诱导性关节炎（CIA）大鼠骨破坏作用机制及对滑膜成纤维细胞（FLS）体外增殖的影响。方法    本研究首先利用牛Ⅱ型胶原建立SD大鼠CIA模型，造模成功后随机分为模型组、雷公藤多苷组和蒙药森登-4汤高、中、低剂量组，各10只；正常组10只大鼠不造模。各组大鼠给予相应药物，观察各组大鼠踝关节组织病理学改变，检测各组大鼠血清白细胞介素1（IL-1）、IL-6、IL-17、肿瘤坏死因子α（TNF-α）等细胞因子含量，检测Wnt信号通路关键因子DKK1蛋白在爪关节中的表达。随机取1只CIA大鼠分离FLS行体外培养，实验分为空白对照组、雷公藤多苷组及高、中、低剂量蒙药森登-4汤含药血清组，干预24、48、72 h后检测CIA-FLS增殖情况。结果    各用药组大鼠滑膜增生、细胞浸润及骨破坏评分较模型组均有不同程度下调，其中雷公藤多苷组和蒙药森登-4汤高剂量组下调最为明显［（1.10±0.57）、（1.20±0.42）分比（2.80±0.42）分；（1.10±0.88）、（1.10±0.32）分比（2.90±0.32）分；（0.90±0.57）、（1.30±0.48）分比（2.70±0.48）分］（均P＜0.01）。各用药组大鼠血清IL-1、IL-6、IL-17、TNF-α水平和爪关节DKK1蛋白表达水平与模型组比较均有所下降。高、中剂量蒙药森登-4汤含药血清组和雷公藤多苷组干预24、48、72 h后，以及低剂量蒙药森登-4汤含药血清组干预48、72 h后，均可明显抑制CIA-FLS增殖，与空白对照组比较差异均有统计学意义（均P＜0.05）。结论    蒙药森登-4汤对CIA大鼠具有明显的骨破坏抑制作用，对CIA-FLS体外增殖有明显抑制作用，其作用存在量效关系，蒙药森登-4汤高剂量作用优于中剂量和低剂量。

• 【Abstract】Objective    To explore the mechanism of Mongolian medicine Sendeng-4 decoction in inhibiting bone destruction in collagen-induced arthritis（CIA） rats and its effect on fibroblast-like synoviocyte（FLS） culture in vitro. Methods    CIA model of SD rats was established using bovine collagen type Ⅱ. SD rats were randomly divided into normal group, model control group, tripterygium wilfordii polyglycoside group and high, medium, low dose of Mongolian medicine Sendeng-4 decoction groups, with 10 rats in each group. Histopathological changes of ankle joint were observed. Levels of serum interleukin-1(IL-1), IL-6, IL-17 and tumor necrosis factor-α(TNF-α) were detected. Expression of DKK1 protein, the key factor of Wnt signaling pathway, in claw joint was detected. CIA-FLS was isolated from 1 rat, cultured in vitro and divided into blank control group, tripterygium wilfordii polyglycoside group and high, medium, low dose of Mongolian medicine Sendeng-4 decoction groups. Proliferation of CIA-FLS was detected 24, 48, 72 h after drug intervention. Results    Scores of synovial hyperplasia, cell infiltration and bone damage were down-regulated in drug intervention groups compared to those in model control group, especially in tripterygium wilfordii group and high dose of Sendeng-4 decoction group［（1.10±0.57）,（1.20±0.42） vs （2.80±0.42）； （1.10±0.88）,（1.10±0.32） vs （2.90±0.32）； （0.90±0.57）,（1.30±0.48） vs （2.70±0.48）］（all P＜0.01）. Levels of IL-1, IL-6, IL-17, TNF-α and expression of DKK1 protein in drug intervention groups were lower than those in model control group. Compared to blank control group, CIA-FLS proliferation was significantly inhibited in high and medium dose Sendeng-4 decoction groups at 24, 48, 72 h after intervention and in low dose Sendeng-4 decoction group at 48 and 72 h after intervention(all P＜0.01). Conclusion    Mongolian medicine Sendeng-4 decoction shows dose-dependent inhibition on bone destruction in CIA rats and vitro culture of CIA-FLS.