中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (33): 5348-5353.doi: 10.3969/j.issn.2095-4344.2017.33.016

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

人胎盘来源间充质干细胞对糖尿病孕鼠血清及胎盘组织中相关生化指标的影响

杨作峰，王 影，裴玲玲，沈晓桐，陈梦鸽，赵 佳，张 楠，刘 伟   

  1. 沈阳医学院附属中心医院产科，辽宁省沈阳市 110024
  • 修回日期:2017-10-22 出版日期:2017-11-28 发布日期:2017-12-01
  • 通讯作者: 刘伟，主任医师，沈阳医学院附属中心医院产科，辽宁省沈阳市 110024
  • 作者简介:杨作峰，男，1990年生，山东省济宁市人，汉族，沈阳医学院在读硕士，主要从事妊娠合并症临床及基础研究。
  • 基金资助:

    辽宁省自然科学基金指导计划(201602724)

Biochemical changes in the serum and placenta of rats with gestational diabetes after transplantation of human placental mesenchymal stem cells

Yang Zuo-feng, Wang Ying, Pei Ling-ling, Shen Xiao-tong, Chen Meng-ge, Zhao Jia, Zhang Nan, Liu Wei   

  1. Department of Obstetrics, Central Hospital of Shenyang Medical University, Shenyang 110024, Liaoning Province, China
  • Revised:2017-10-22 Online:2017-11-28 Published:2017-12-01
  • Contact: Liu Wei, Chief physician, Department of Obstetrics, Central Hospital of Shenyang Medical University, Shenyang 110024, Liaoning Province, China
  • About author:Yang Zuo-feng, Studying for master’s degree, Department of Obstetrics, Central Hospital of Shenyang Medical University, Shenyang 110024, Liaoning Province, China
  • Supported by:

    Liaoning Provincial Natural Science Foundation Guidance Program, No. 201602724

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摘要：

文章快速阅读：

文题释义：
胰高血糖素：它是伴随胰岛素由脊椎动物胰脏的胰岛α细胞分泌的一种激素。与胰岛素的作用相反，胰高血糖素是一种促进分解代谢的激素。胰高血糖素具有很强的促进糖原分解和糖异生作用，使血糖明显升高，1 mol/L的激素可使3×106 mol/L的葡萄糖迅速从糖原分解出来。胰高血糖素通过cAMP-PK系统，激活肝细胞的磷酸化酶，加速糖原分解。胰高血糖素还可激活脂肪酶，促进脂肪分解，同时又能加强脂肪酸氧化，使酮体生成增多。胰高血糖素产生上述代谢效应的靶器官是肝，切除肝或阻断肝血流，这些作用便消失。
脂联素：脂肪组织主要由大量聚集成团的脂肪细胞构成，脂联素(Adiponectin/ADPN)是脂肪细胞分泌的一种内源性生物活性多肽或蛋白质。脂联素是一种胰岛素增敏激素，能改善小鼠的胰岛素抗性和动脉硬化症；对人体的研究发现，脂联素水平能预示2型糖尿病和冠心病的发展，并在临床试验中表现出抗糖尿病、抗动脉粥样和炎症的潜力。

 

摘要
背景：人胎盘来源间充质干细胞能够改善糖尿病鼠及糖尿病孕鼠的血糖水平，但对其血清及胎盘组织中胰高血糖素、脂联素、肿瘤坏死因子α等指标的影响鲜有研究。
目的：探究人胎盘来源间充质干细胞对糖尿病孕鼠血清及胎盘组织中胰高血糖素、脂联素、肿瘤坏死因子α等指标的影响。
方法：用高脂高糖饮食+低剂量链脲佐菌素注射方法制备糖尿病孕鼠模型，于妊娠第4，11天将第3代人胎盘来源间充质干细胞混悬液0.5 mL(1×1010 L-1)经尾静脉注入糖尿病孕鼠体内，对照组经尾静脉注射等量生理盐水。于妊娠第20天于腹主动脉抽血，然后行剖宫产术取出胎盘，采用ELISA法检测血清中胰高血糖素、脂联素、肿瘤坏死因子α水平；用real-time PCR检测上述指标在胎盘组织中的表达。
结果与结论：①人胎盘间充质干细胞第4天干预组与人胎盘间充质干细胞第11天干预组孕鼠血清胰高血糖素、脂联素、肿瘤坏死因子α水平差异无显著性意义(P > 0.05)，胎盘组织中胰高血糖素、脂联素、肿瘤坏死因子α mRNA表达量差异无显著性意义(P > 0.05)；②与生理盐水第4天干预组相比，人胎盘间充质干细胞第4天干预组孕鼠血清脂联素水平明显升高，差异有显著性意义(P < 0.05)；人胎盘间充质干细胞第4天干预组孕鼠胎盘组织中胰高血糖素的mRNA表达量明显降低，差异有显著性意义(P < 0.05)；③与生理盐水第11天干预组相比，人胎盘间充质干细胞第11天干预组孕鼠血清胰高血糖素水平和胎盘组织中胰高血糖素的mRNA表达量均明显降低，差异有显著性意义(P < 0.01)，而肿瘤坏死因子α水平明显升高，差异有显著性意义(P < 0.01)；④结果表明，人胎盘间充质干细胞能够影响糖尿病孕鼠脂联素、胰高血糖素水平，从而为胎盘间充质干细胞改善糖尿病孕鼠血糖的可能作用机制提供进一步研究思路。糖尿病孕鼠于妊娠早期或晚期给予胎盘间充质干细胞对上述指标无明显影响。

 

关键词: 干细胞, 人胎盘来源间充质干细胞, 培养, 糖尿病孕鼠, 胰高血糖素, 脂联素, 肿瘤坏死因子α, 辽宁省自然科学基金

Abstract:

BACKGROUND: Human placental mesenchymal stem cells can improve the blood glucose level of diabetes mellitus rats and gestational diabetes rats, but little is reported on its effect on glucagon, adiponectin, and tumor necrosis factor-α in the serum and placental tissues.
OBJECTIVE: To investigate the effects of human placental mesenchymal stem cells on the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues in gestational diabetes rats.
METHODS: A rat model of gestational diabetes was made by high-fat and high-sugar diet plus low-dose injection of streptozotocin. Passage 3 human placental mesenchymal stem cell suspension (1×1010 cells/L, 0.5 mL) was injected into gestational diabetes rats at gestational days 4 and 11 (4- and 11-day intervention groups). Meanwhile, control rats were given the same amount of normal saline. At 20 days of gestation, blood samples from the abdominal aorta were extracted, and then cesarean section was made to remove the placenta in the gestational diabetes rats. ELISA and real-time PCR were used to detect the levels of glucagon, adiponectin and tumor necrosis factor-α in the serum and placental tissues, respectively. 
RESULTS AND CONCLUSION: (1) The serum and placental levels of glucagon, adiponectin and tumor necrosis factor-α showed no differences between the 4- and 11-day intervention groups (P > 0.05). (2) Compared with the control group, significantly increased serum adiponectin level and significantly decreased placental glucagon mRNA expression were found in the 4-day intervention group (P < 0.05). (3) Compared with the control group, the serum adiponectin level and the placental glucagon level both had a significant decrease in the 11-day intervention group (P < 0.01), while the serum level of tumor necrosis factor-α was significantly decreased (P < 0.01). To conclude, transplantation of human placental mesenchymal stem cells can vary the adiponectin and glucagon levels, which provides a new research idea and basis for the further study on the possible mechanism of placental mesenchymal stem cells to improve blood glucose level in gestational diabetes rats. Additionally, it is worthy while to notice that gestational diabetes rats given placental mesenchymal stem cells in the early or late pregnancy show no effects on the above indicators.

 

Key words: Placenta, Mesenchymal Stem Cell Transplantation, Diabetes, Gestational, Glucagon, Adiponectin, Tumor Necrosis Factor-alpha, Tissue Engineering

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