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丹皮酚对强直性脊柱炎模型小鼠Wnt和BMP/Smad信号转导通路的影响
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| 篇名： | 丹皮酚对强直性脊柱炎模型小鼠Wnt和BMP/Smad信号转导通路的影响 |
| TITLE： | |
| 摘要： | 目的：研究丹皮酚对强直性脊柱炎（AS）模型小鼠分泌型糖蛋白（Wnt）和骨形态发生蛋白（BMP）/细胞信号转导分子（Smad）通路的影响，探讨丹皮酚防治AS的机制。方法：将40只小鼠随机分为正常组、模型组、柳氮磺吡啶组（阳性对照，9 mg/kg）和丹皮酚组（3 mg/kg），每组10只。除正常组外的其余各组小鼠均采用完全弗氏佐剂+蛋白聚糖腹腔注射法复制AS模型。各给药组小鼠在成模后灌胃相应药物，正常组和模型组小鼠灌胃等体积蒸馏水，每天给药1次，连续20 d。末次给药后处死小鼠，透射电镜下观察各组小鼠骶髂关节滑膜细胞超微病理结构变化，采用酶联免疫吸附法检测小鼠血清中肿瘤坏死因子α（TNF-α）、Wnt信号通路病理性骨化相关因子（DKK-1）含量，实时荧光定量聚合酶链式反应法检测小鼠滑膜组织中骨形态发生蛋白2（BMP-2）、细胞内核心结合因子α1（Cbfα1）、Smad1 mRNA表达。结果：与正常组比较，模型组小鼠血清中TNF-α含量明显增加、DKK-1含量明显减少，滑膜组织中BMP-2、Cbfα1和Smad1 mRNA表达水平明显升高，差异均有统计学意义（P＜0.05或P＜0.01）；电镜下可见模型组小鼠滑膜细胞增生，排列紊乱，分泌活性细胞器分泌亢进，细胞间隙增宽。与模型组比较，柳氮磺吡啶组和丹皮酚组小鼠血清中TNF-α含量均明显减少，丹皮酚组小鼠血清中DKK-1含量明显增加，滑膜组织中BMP-2、Cbfα1和Smad1 mRNA表达水平明显降低，差异均有统计学意义（P＜0.05或P＜0.01）；电镜下可见丹皮酚组小鼠滑膜细胞线粒体、溶酶体、粗面内质网的形态明显改善。结论：丹皮酚防治AS的机制可能与降低血清中TNF-α含量、升高血清中DKK-1含量，下调滑膜细胞中BMP-2、Cbfα1和Smad1 mRNA表达，抑制Wnt和BMP/Smad骨化相关信号转导通路逆转滑膜细胞成骨分化有关。 |
| ABSTRACT： | OBJECTIVE： To study the effects of paeonol on Wnt and BMP/Smad pathway in ankylosing spondylitis （AS） model mice， and to investigate prevention and treatment mechanism of paeonol for AS. METHODS： 40 mice were randomly divided into normal group， model group， sulfasalazine group （positive control， 9 mg/kg） and paeonol group （3 mg/kg）， with 10 mice in each group. In addition to the normal group， Freund’s adjuvant and proteoglycan were used to establish AS model in each group. After modeling， mice in each administration group were given relevant medicine intragastrically； normal group and model group were given constant volume of distilled water intragastrically， once a day， for consecutive 20 d. After last administration， the mice were killed， TEM was used to observe the ultrastructural pathologic change of synovial cells in articulationes sacroiliaca. The serum contents of TNF-α and DKK-1 were determined by ELISA， and the mRNA expressions of BMP-2， Cbfα1 and Smad1 in synovial tissue were detected by real-time fluorescent quantitative PCR. RESULTS： Compared with normal group， serum content of TNF-α in model group was increased significantly， while serum content of DKK-1 was decreased significantly； mRNA expressions of BMP-2， Cbfα1 and Smad1 in synovial tissue were increased significantly， with statistical significance （P＜0.05 or P＜0.01）. Under the electron microscope， the synoviocytes of mice in model group were proliferated and arranged in disorder， and the secretory activity of active organelles were hyperactivity and the gap among cells became widened. Compared with model group， serum content of TNF-α in sulfasalazine group and paeonol group were decreased significantly； serum content of DKK-1 was increased significantly and mRNA expressions of BMP-2， Cbfα1 and Smad1 in synovial tissue were decreased significantly in paeonol group， with statistical significance （P＜0.05 or P＜0.01）. Electron microscopy showed that mitochondria， lysosome and rough endoplasmic reticulum structure of synovial cell were improved significantly in paeonol group. CONCLUSIONS： The mechanism prevention and treatment of paeonol on AS may be associated with reducing serum content of TNF-α， increasing serum content of DKK-1， down-regulating mRNA expressions of BMP-2， Cbfα1 and Smad1 in synovial cells， inhibiting Wnt and BMP/Smad ossification related signal transduction pathway and reversing osteogenic differentiation of synovial cells. |
| 期刊： | 2018年第29卷第11期 |
| 作者： | 吴琪，吴倩，周晓红，吴玲慧 |
| AUTHORS： | WU Qi，WU Qian，ZHOU Xiaohong，WU Linghui |
| 关键字： | 丹皮酚；强直性脊柱炎；分泌型糖蛋白；骨形态发生蛋白/细胞信号转导分子；小鼠 |
| KEYWORDS： | Paeonol； Ankylosing spondylitis； Wnt； BMP/Smad； Mice |
| 阅读数： | 297 次 |
| 本月下载数： | 7 次 |
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