摘要
背景:目前多数研究集中于探讨骨髓间充质干细胞移植后的转分化及其调控机制,而缺少干细胞移植治疗糖尿病的方法学和功能学研究。目的:观察不同途径移植骨髓间充质干细胞对糖尿病模型鼠的治疗效果。设计、时间及地点:随机对照动物实验,于2008-03/11在深圳市人民医院临床研究中心完成。材料:1周龄雄性SD大鼠4只,用于制备骨髓间充质干细胞。8周龄雌性SD大鼠32只,随机分为胰腺包膜下移植组、静脉移植组、糖尿病对照组、正常对照组,8只/组。方法:全骨髓法体外分离培养大鼠骨髓间充质干细胞,贴壁法纯化扩增。胰腺包膜下移植组、静脉移植组、糖尿病对照组大鼠通过腹腔注射链脲佐菌素建立糖尿病模型。造模后,胰腺包膜下移植组取5×106个第3代骨髓间充质干细胞,重悬于0.2mLPBS中,多点注射至胰腺包膜下;静脉移植组经股静脉注射等量骨髓间充质干细胞悬液;糖尿病对照组及正常对照组不接受任何处理。主要观察指标:动态观察移植后血糖、胰岛素、C-肽水平变化,以及糖耐量实验结果。结果:与糖尿病对照组比较,移植后30d内胰腺包膜下移植组和静脉移植组血糖值均明显降低(P<0.05),且胰腺包膜下移植组下降幅度更为显著(P<0.05);移植后第2,4,6周胰腺包膜下移植组与静脉移植组的胰岛素、C-肽水平均明显升高(P<0.05),且胰腺包膜下移植组升高幅度更为显著(P<0.05),但仍低于正常对照组(P<0.05)。糖耐量实验中腹腔注射葡萄糖后,胰腺包膜下移植组血糖水平30min达峰值,90min降低至空腹水平,接近正常对照组的葡萄糖处理能力;静脉移植组对葡萄糖的处理能力略强于糖尿病对照组(P<0.05),但此2组在180min内均未能恢复到正常血糖水平。结论:骨髓间充质干细胞移植途径与糖尿病的治疗效果有直接关系,胰腺包膜下移植效果优于静脉移植。
BACKGROUND： Present studies explored transdifferentiation and regulatory mechanism of bone marrow mesenchymal stem cells （BMSCs） after transplantation. Studies concerning methodology and function of stem cell transplantation for treating diabetes are rare. OBJECTIVE： To study the effects of different transplantation of BMSCs in diabetic model rats. DESING, TIME AND SETTING： The randomized controlled animal study was performed at the Clinical Research Center of Shenzhen People＇s Hospital from March to November 2008. MATERIALS： Four male Sprague Dawley rats aged 1 week were used for establishing BMSCs. Thirty-two female Sprague Dawley rats aged 8 weeks were equally and randomly divided into pancreas peplos transplantation group, vein transplantation group, diabetes control group, and normal control group. METHODS： Rat BMSCs were isolated and culture by the whole bone marrow method, and then purified and amplified by adherence. Rats in the pancreas peplos transplantation group, vein transplantation group and diabetes control group were abdominally injected with streptozotocin to establish diabetes models. Following model establishment, at the third passage of BMSCs at 5×10^6 was suspended into the 0.2 mL phosphate buffered saline, and multiply injected into pancreas peplos in the pancreas peplos transplantation group. In the vein transplantation group, rats were subjected to an equal volume of BMSC suspension via the vein. Rats in the diabetes control group and normal control group were left intact. MAIN OUTCOME MEASURES： Following transplantation, blood glucose, insulin, C-peptide level changes, and glucose tolerance were observed dynamically. RESULTS： Compared with diabetic control group, blood glucose value significantly decreased in the pancreas peplos transplantation group and vein transplantation group within 30 days following transplantation （P 〈 0.05）, and the decrease range in the pancreas peplos transplantation group was mostly significant （P 〈 0.05）. At 2, 4 and 6 days following transplantation, insulin and C-peptide levels significantly increased in the pancreas peplos transplantation group and vein transplantation group （P 〈 0.05）, and the increase range was significant in the pancreas peplos transplantation group （P 〈 0.05）, but still tower than in the normal control group （P 〈 0.05）. Following intraperitoneal injection of glucose, blood glucose levels peaked at 30 minutes, decreased to fasting leveling at 90 minutes, and the glucose treatment ability was nearly to normal control group in the pancreas peplos transplantation group. The treatment ability to glucose in the vein transplantation group was slightly stronger compared with the diabetes control group （P 〈 0.05）, but the levels did not reach a normal blood glucose level within 180 minutes in this two groups. CONCLUSION： Pathway of BMSC transplantation has direct relationship with treatment of diabetes. Pancreas peplos transplantation has better effects compared with the vein transplantation.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2009年第19期3675-3679,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
国家973前期专项基金(2007CB516811)
广东省自然科学基金(6027540)
深圳市科技局重点项目(200601015)~~
