rhPDGF-BB对糖尿病大鼠骨髓基质干细胞迁移的促进作用

doi:10.19439/j.sjos.2018.06.004

上海口腔医学 ›› 2018, Vol. 27 ›› Issue (6): 579-584.doi: 10.19439/j.sjos.2018.06.004

rhPDGF-BB对糖尿病大鼠骨髓基质干细胞迁移的促进作用

王德芳, 刘燕, 王珏

上海市口腔病防治院口腔修复科,复旦大学附属口腔医院口腔生物医学工程实验室,上海 200001

收稿日期:2018-07-02 出版日期:2018-12-25 发布日期:2019-01-11
通讯作者: 刘燕,E-mail：liuyan548@126.com
作者简介:王德芳（1962-）,女,本科,主任医师,E-mail：wangdefang6243@126.com

rhPDGF-BB promotes migration of bone marrow stromal stem cells in diabetic rats

WANG De-fang, LIU Yan, WANG Jue

Department of Prosthodontics, Shanghai Stomatological Hospital, Fudan University; Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University. Shanghai 200001, China

Received:2018-07-02 Online:2018-12-25 Published:2019-01-11
Supported by:
上海市卫生和计划生育委员会青年项目（20154Y0154）

摘要/Abstract

摘要： 目的: 体外评价不同浓度人重组血小板衍生生长因子BB（recombinant human platelet derived growth factor-BB, rhPDGF-BB）对糖尿病大鼠骨髓基质干细胞（BMSCs）迁移的影响,以及基质细胞衍生因子（stromal cell-derived factor 1,SDF-1）和其G 蛋白偶联受体CXCR4调控作用的相关机制,为rhPDGF-BB应用于临床糖尿病患者相关骨修复再生治疗提供理论基础。方法: 建立链脲佐菌素诱导的糖尿病大鼠动物模型。体外培养糖尿病大鼠BMSCs,作为对照组。采用Transwell小室趋化模型,以浓度0、10、50、100 ng/mL rhPDGF-BB作用BMSCs,检测其体外趋化作用;定时定量RCR检测BMSCs SDF-1、CXCR4 mRNA的表达变化,筛选出药物最佳作用浓度;应用PI3K/Akt抑制剂,反向证实rhPDGF-BB对BMSCs的SDF-1、CXCR4表达的调节作用。采用SPSS 17.0软件包对数据进行统计学分析。结果: 链脲佐菌素诱导的糖尿病大鼠,1周后选取大鼠尾静脉血糖浓度高于16.7 mmol/L者为建模成功大鼠。与糖尿病大鼠的BMSCs相比,rhPDGF-BB促进糖尿病大鼠BMSCs的迁移,50 ng/mL rhPDGF-BB为促进糖尿病大鼠BMSCs迁移的最佳作用浓度,PI3K/Akt抑制剂明显抑制糖尿病大鼠BMSCs的迁移。结论: rhPDGF-BB促进糖尿病大鼠BMSCs的迁移,并通过SDF-1/CXCR4轴,调节糖尿病大鼠BMSCs的迁移。

关键词: 人重组血小板衍生生长因子BB, 糖尿病大鼠骨髓基质干细胞, 迁移, 糖尿病

Abstract: PURPOSE: To evaluate the effect of different concentrations of rhPDGF-BB on bone marrow stromal stem cells(BMSCs) migration in diabetic rat, and related mechanisms of SDF-1 and its G-protein conjugated receptor regulation, provide a theoretical basis for the application of rhPDGF-BB to diabetic patients for bone regeneration therapy. METHODS: Animal model with diabetes were induced by streptozotocin in rats. BMSCs of diabetic rats were cultured in vitro as the control group. Transwell chemokinesis model was adopted to detect the chemokinesis of BMSCs in vitro with rhPDGF-BB at concentrations of 0, 10, 50, and 100 ng/mL, and real-time PCR was used to detect the expression of BMSCs SDF-1, CXCR4 mRNA, determine the optimum concentration of the drug. The regulatory effects of rhPDGF-BB on SDF-1 and CXCR4 expression of BMSCs were confirmed in reverse with PI3K/Akt inhibitor. Statistical analysis of the data was performed using SPSS 17.0 software package. RESULTS: In diabetic rats induced by streptozotocin, one week later, the rat tail vein blood glucose concentration higher than 16.7 mmol/L was selected as the successful model rats. Compared with BMSCs in diabetic rats, rhPDGF-BB promoted BMSCs migration in diabetic rats, 50 ng/mL rhPDGF-BB was the optimal concentration in diabetic rats, and PI3K/Akt inhibitors significantly inhibited the migration of BMSCs in diabetic rats. CONCLUSIONS: rhPDGF-BB promotes the migration of diabetic rat BMSCs and regulates its migration by regulating SDF-1/CXCR4 axis.

Key words: rhPDGF-BB, BMSCs, Migration, Diabetes mellitus

中图分类号:

R783.4

王德芳, 刘燕, 王珏. rhPDGF-BB对糖尿病大鼠骨髓基质干细胞迁移的促进作用[J]. 上海口腔医学, 2018, 27(6): 579-584.

WANG De-fang, LIU Yan, WANG Jue. rhPDGF-BB promotes migration of bone marrow stromal stem cells in diabetic rats[J]. Shanghai Journal of Stomatology, 2018, 27(6): 579-584.

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rhPDGF-BB对糖尿病大鼠骨髓基质干细胞迁移的促进作用

rhPDGF-BB promotes migration of bone marrow stromal stem cells in diabetic rats

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