胎盘间充质干细胞移植对类风湿关节炎 大鼠炎症因子及软骨破坏的影响

Therapeutic effect of placenta mesenchymal stem cell transplantation on inflammatory factors and cartilage destruction in rheumatoid arthritis rats

摘要:

目的 分析胎盘间充质干细胞移植对类风湿关节炎大鼠炎症因子及软骨破坏的改善作用。方法 将32 只SD 大鼠随机分为4 组，实验组、对照组、模型组及对照组，每组8 只。实验组、对照组和模型组为 复制类风湿关节炎动物模型，正常组不做任何处理（n =8）。造模后12 h，实验组尾静脉注射胎盘间充质干细胞， 对照组注射等量鼠成纤维细胞，模型组不干预。干预3 周后，处死所有大鼠，酶联免疫吸附实验与qRT-PCR 检测。结果 ①模型组、对照组与正常组比较，TNF-α、IL-1β 及IL-6 水平均升高，差异有统计学意义（P <0.05）； 实验组与模型组及对照组比较，TNF-α、IL-1β 及IL-6 水平降低，差异有统计学意义（P <0.05）；实验组转 化生长因子β（TGF-β）水平高于其余各组，差异有统计学意义（P <0.05）；②模型组、对照组与正常组比 较，滑膜组织基质金属蛋白酶1（MMP-1）、基质金属蛋白酶3（MMP-3）及基质金属蛋白酶13（MMP-13） mRNA 升高，差异有统计学意义（P <0.05）；实验组与对照组及模型组比较，MMP-1、MMP-3 及MMP-13 mRNA 水平降低，差异有统计学意义（P <0.05）。实验组、对照组、模型组与正常组比较，基质金属蛋白酶抑 制物3 mRNA 降低，差异有统计学意义（P <0.05）。模型组、对照组与正常组比较，钙黏素11 mRNA 升高， 差异有统计学意义（P <0.05）；实验组与模型组、对照组比较，钙黏素11 水平降低，差异有统计学意义（P <0.05）。 结论 胎盘间充质干细胞可能通过抑制TNF-α、IL-1β、IL-6 水平及MMP 分泌与钙黏素11 表达，上调 TGF-β 水平，来减轻类风湿关节炎大鼠的关节炎症与软骨破坏。

Abstract:

Objective To investigate the therapeutic effect of placenta mesenchymal stem cells (PMSC) transplantation on inflammatory factors and cartilage destruction in rheumatoid arthritis rats. Methods Totally 32 SD rats were randomly divided into experimental group (RA rats receiving PMSC) (n = 8), control group (RA rats receiving fibroblast cells) (n = 8), model group (RA rats without any treatments) (n = 8), and normal group(normalrats without any treatments) (n = 8). Rats received intravenous injection of cells 12 h after modeling. All rats were sacrificed 3 weeks after intervention. ELISA and PT-PCR were performed for further analysis. Results Levels of TNF-α, IL-1β and IL-6 were elevated in model group and control group when compared with normal control group (P < 0.05) while rats in experimental group experienced significantly lower levels of TNF-α, IL-1β and IL-6 when compared with model group. Expression of TGF-β was dramatically increased in experimental group when compared with remaining groups (P < 0.05). Levels of MMP-1, MMP-3 and MMP-13 were upregulated in model group and control group when compared with normal control group (P < 0.05) while rats in experimental group experienced significantly lower levels of MMP-1, MMP-3 and MMP-13 when compared with model group (P < 0.05). Levels of synovial cadherin-11 were upregulated in model group and control group when compared with normal control group (P < 0.05), while rats in experimental group experienced significantly lower levels of synovial cadherin-11 when compared with model group (P < 0.05). Conclusions Placenta derived mesenchymal stem cells reduce joint inflammation and cartilage destruction through reduction of TNF-α, interleukin 1, interleukin 6, MMPs, and cadherin-11 as well as upregulation of TGF-β in rats with rheumatoid arthritis.