中国组织工程研究

中国组织工程研究 ›› 2012, Vol. 16 ›› Issue (19): 3529-3534.doi: 10.3969/j.issn.1673-8225.2012.19.023

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

异种脐血干细胞移植胶原性关节炎小鼠基质金属蛋白酶2及基质金属蛋白酶9 mRNA的表达*☆

牛广华，高玉洁，都  静，郭  鹤，王柏山，高明利   

  1. 辽宁中医药大学附属医院临床检验中心，辽宁省沈阳市  110032
  • 收稿日期:2011-12-08 修回日期:2012-04-05 出版日期:2012-05-06 发布日期:2012-05-06
  • 通讯作者: 高玉洁，主任技师，辽宁中医药大学附属医院临床检验中心，辽宁省沈阳市 110032
  • 作者简介:牛广华☆，男，1972年生，辽宁省锦州市人，满族，2010年辽宁中医药大学毕业，博士，副主任技师，主要从事自身免疫性疾病研究。
  • 基金资助:

    辽宁省自然基金资助项目(20092033)。

Matrix metalloproteinase-2 and matrix metalloproteinase-9 mRNA expression in mice with collagen-induced arthritis following heterogenous umbilical cord blood stem cell transplantation*☆

Niu Guang-hua, Gao Yu-jie, Du Jing, Guo He, Wang Bai-shan, Gao Ming-li   

  1. Center for Clinical Laboratory, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang  110032, Liaoning Province, China
  • Received:2011-12-08 Revised:2012-04-05 Online:2012-05-06 Published:2012-05-06
  • Contact: Gao Yu-jie, Chief technician, Center for Clinical Laboratory, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China jie_54@sohu.com
  • About author:Niu Guang-hua☆, M.D., Associate chief technician, Center for Clinical Laboratory, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110032, Liaoning Province, China ngh@263.net
  • Supported by:

    the Natural Science Foundation of Liaoning Province, No. 20092033*

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摘要：

背景:基质金属蛋白酶对细胞外基质的降解是类风湿关节炎患者关节破坏的必要环节，基质金属蛋白酶2，9可以作为类风湿关节炎病情评估及有无关节进行性破坏的预测指标。
目的:观察异种异基因脐血干细胞移植对Ⅱ型胶原性关节炎小鼠脾组织基质金属蛋白酶2，9表达的影响。
方法:无菌取胎儿脐血，分离脐血干细胞。将C57BL/6(H-2b)小鼠分为5组，每组10只。除正常对照组外，氟氏完全佐剂+Ⅱ型胶原诱导小鼠建立胶原性关节炎模型。甲氨喋呤组以甲氨蝶呤混悬液0.017 5 g/kg灌胃，每5 d 1 次。其余各组均采用尾静脉注射，模型组、正常对照组注射生理盐水，单、双份脐血干细胞移植组注射来源于一个或两个母体的2×106/kg的脐血干细胞。注射后第42天处死动物取踝关节进行病理组织学检测，取脾组织采用反转录-聚合酶链反应法检测基质金属蛋白酶2，9 mRNA的表达。
结果与结论:双份脐血干细胞移植能显著抑制Ⅱ型胶原性关节炎小鼠关节滑膜组织中炎性细胞浸润，修复损伤的软骨组织，修复效果优于甲氨蝶呤组及单份脐血干细胞移植组。双份脐血干细胞移植组脾组织中基质金属蛋白酶2，9 mRNA的表达水平明显低于单份移植组(P < 0.01)，提示异种异基因双份脐血干细胞移植可以通过调控基质金属蛋白酶2，9 mRNA表达，参与类风湿关节炎软骨的病理变化过程及软骨细胞外基质的合成，有效治疗类风湿关节炎。
 

关键词: 基质金属蛋白酶, 脐血干细胞, 细胞移植, 类风湿关节炎, 甲氨蝶呤

Abstract:

BACKGROUND: Matrix metalloproteinase (MMP) degrades extracellular matrix, which is a necessity of joint destruction in rheumatoid arthritis patients. MMP-2 and MMP-9 can evaluate rheumatoid arthritis and serve as an index to predict progressive destruction of the joint.
OBJECTIVE: To observe heterogenous allogeneic umbilical cord blood stem cell (UBSC) transplantation on MMP-2 and MMP-9 expression in the spleen of mice with type Ⅱ collagen-induced arthritis.
METHODS: Fetus cord blood was sterilely obtained and cord blood stem cells were separated. The C57BL/6(H-2b) mice were assigned to five groups (n=10). Except normal control group, models of collagen-induced arthritis were established using complete Freund’s adjuvant + type Ⅱ collagen. Mice from the methopterin group were intragastrically administered methopterin suspension 0.017 5 g/kg, once every 5 days. Other groups used caudal vein injection. Mice from the model and normal control groups were injected with saline. Mice from the mono-UBSCs group and double-UBSCs group were injected with 2×106/kg UBSCs from one and two parents. At 42 days following injection, animals were sacrificed and the ankle joint was obtained for histopathological detection. MMP-2 and MMP-9 mRNA expression in the spleen was examined using reverse transcription-polymerase chain reaction.
RESULTS AND CONCLUSION: Double-UBSC transplantation could significantly inhibit inflammatory cell infiltration in synovial tissue of mice with type Ⅱ collagen-induced arthritis, repaired impaired cartilage tissue. The repair effect was better than that in methopterin group and mono-UBSCs group. MMP-2 and MMP-9 mRNA expression in the spleen was significantly lower in the double-UBSCs group than the mono-UBSCs group (P < 0.01). These suggest that heterogenous allogeneic double-UBSCs transplantation participated in pathological changes in rheumatoid arthritis cartilage and in synthesis of cartilage extracellular matrix and effectively treated rheumatoid arthritis by regulating MMP-2 and MMP-9 mRNA expression.

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