外周血间充质干细胞移植防治兔血管成形术后再狭窄的探讨

Research on PBMSCs transplantation for prevention and treatment of postangioplasty restenosis in rabbits

目的探讨外周血间充质干细胞(MSCs)移植对模型兔颈动脉血管成形术后再狭窄的防治作用。方法新西兰大白兔65只,5只作为产生MSCs的种兔,60只随机分为MSCs移植组和对照组,每组30只,术后7、14、28天处死兔,取颈动脉血管标本通过Weiger弹力纤维染色及免疫组织化学染色进行形态学分析、内皮化程度分析、归巢MSCs的鉴定和分化跟踪等。结果 MSCs移植组术后7、14、28天内膜面积、内膜面积/中膜面积及再狭窄率明显低于对照组(P<0.01):内皮化程度分忻显示,MSCs移植组明显优于对照组(P<0.01)。MSCs移植组术后7、14、28天血管组织中有绿色荧光蛋白(GFP)阳性细胞分布,且部分细胞同时为GFP和CD31阳性,但在未损伤血管及对照组则无。结论静脉移植外周血MSCs能促进模型兔颈动脉球囊成形术后损伤血管的快速内皮化,抑制内膜增生和减少术后再狭窄:这一有益作用可能与MSCs归巢到损伤血管局部并部分分化为内皮细胞有关。

Objective To investigate the possible mechanism of PBMSCs from bone marrow cells mobilization in prevention and cure restenosis after carotid angioplasty in model rabbits . Methods MSCs were collected from 5 rabbits,and other 60 New Zealand white male rabbits undergoing carotid atherosclerotic stenosis were randomly divided into two groups,MSCs transplanted group （n = 30） and control group （n = 30）. The animals were sacrificed 7,14,28 days after operation and the blood vessel specimens were taken for morphometric analysis of injured carotid artery neointima formation,immunohistochemical analysis of the transplanted cells homing and differen- tiation,and injured carotid artery reendothelialization. Results Neointimal thickening was observed in all balloon-injured vessels. Seven, 14,28 days after operation, neointimal area,neointimal area/media area and restenosis rate significantly reduced,and the injured carotid artery reendothe-lialization significantly increased in MSCs transplanted group as compared with the control group. GFP-positive cells in the injused carotid artery area were obsered only in the MSCs transplanted group and some GFP-positive cells were CD31-positive （endotheliocytes）. Conclusions Intravenous transplantation of PBMSCs accelerates reendothelialization and attenuates neointimal thickening and restenosis in rabbit carolid balloon-induced injury model. The beneficial effects may be ascribed to MSCs homing to the injured vessel and differentiating into endotheliocytes.