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

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

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 m L(1×10^(10) 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αm RNA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m RNA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m RNA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。

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-αin 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-αin 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.Passage3human placental mesenchymal stem cell suspension(1×1010cells/L,0.5mL)was injected into gestational diabetes rats at gestational days4and11(4-and11-day intervention groups).Meanwhile,control rats were given the same amount of normal saline.At20days 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-αin the serum and placental tissues,respectively.RESULTS AND CONCLUSION:(1)The serum and placental levels of glucagon,adiponectin and tumor necrosis factor-αshowed no differences between the4-and11-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 the4-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 the11-day intervention group(P<0.01),while the serum level of tumor necrosis factor-αwas 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.