【摘要】 目的 探讨人脐带间充质干细胞(hUC-MSCs)不同移植方式对大鼠糖尿病足(DF)的影响。方法 37只Wistar雄性大鼠随机分为实验组(n=32)和对照组(Con,n=5)。实验组高脂饲料喂养两个月后造模成功,腹腔注射STZ 30mg/kg,重复2~3次直至出现高血糖,Con组注射等体积、等次数的缓冲液。造模成功后将造模组(Mod)随机分为模型组(DM)、局部低剂量组(LD,0.5×106/0.2ml)、局部高剂量组(HD,1.0×106/0.2ml)和静脉组(VI,2.0×106/0.2 ml),每组各5只。各组足背部切除1块约3mm×7mm矩形全层皮肤组织,第2天按分组移植干细胞,比较各组溃疡愈合时间和溃疡面积。结果 hUC-MSCs表面标记为CD 29、CD 44、CD 90和CD l105高表达;20只大鼠造模成功,STZ注射后14d血糖为(21.54±2.71)mmol/L,伴多饮、多尿、消瘦等症状,注射后7d体重低于Con组[(519.08±68.79)vs(577.50±47.86)g,P<0.05]。细胞移植8d后比较各组间皮肤溃疡面积,结果显示,与细胞移植时的溃疡面积比较,DM组溃疡面积为33.1%,HD组、VI组及Con组皮肤溃疡面积分别为26.6%、23.0%和21%,溃疡面积缩小(P<0.05);LD组溃疡面积为33.5%;伤口痊愈时检测血清中VEGF,结果显示,与DM组[(25.17±9.88)pg/ml]比较,Con组[(83.12±19.13)pg/ml]及LD组[(75.15±37.59)pg/ml]含量差异有统计学意义(P<0.01);与DM组比较,VI组TG、TC降低,C-P水平升高。结论 两种hUC-MSCs移植方法在促进糖尿病伤口愈合方面机制不同,静脉移植有利于改善糖尿病整体代谢情况。更多还原

【Abstract】 Objective To observe the effects of different transplant approaches of humam umbilicial cord derived mesenchymal stem cells(hUC-MSCs)on the recovery of diabetic foot(DF)in rats.Methods 37 male Wistar rats were randomly divided into experimental group(n=32)and control group(Con,n=5).Rats in experimental group have been feed with high lipid fodder for two months.Then,STZ(30 mg/kg)was intraperitoneally injected for 2~3 times to establish the experimental model.The control group was injected with equal volume of the buffer.After modeling,the rats were randomly divided into 4 groups:model group(DM),local low dose group(LD,0.5×106 cells/0.2 ml),local high dose group(HD,1.0×106 cells/0.2 ml)and venous group(VI,2×106 cells/0.2 ml),5 in each group.A full-thickness 3 mm×7 mm rectangular skin tissue was removed from foot back to create a skin wound in each rat.Stem cell transplantation was performed according to different groups on the second day.The ulcer healing time and ulcer area were compared. Results Markers CD 44,CD 90,CD 29 and CD 105 had high expression on hUC-MSCs.20 rats were successfully modeled,accompanied by symptoms such as polydipsia,polyuria,and weight loss.The blood glucose was(21.54±2.71)mmol/L at 14 days after STZ injection.At 7 days after STZ injection,the body weight was lower than that of the Con group[(519.08±68.79)vs(577.50±47.86)g,P<0.05].After 8 days of transplantation,the proportion of unhealed ulcer area was 33.1%,26.6%,23.0% and 21% in DM,HD,VI and Con group,respectively(P<0.05).The ulcer area was33.5%left in LD group.Compared with model group,the vascular endothelial growth factor(VEGF)when the wound is healed was higher in LD group [(75.15±37.59)vs(25.17±9.88)pg/ml];serum triglyceride(TG)and total cholesterol(TC)decreased and serum C peptide increased significantly in venous group. Conclusion Local or intravenous administration of hUC-MSCs promote the wound healing of DF in rats by different mechanisms.Intravenous transplantation is more beneficial for improving the overall metabolism.更多还原