静脉注射间充质干细胞对兔颈动脉易损斑块的影响

Effect of intravenous mesenchymal stem cells infusion on vulnerable plaques in carotid of rabbits

目的探讨静脉注射骨髓间充质干细胞(MSC)对动脉粥样硬化易损斑块(VP)稳定性的影响。方法选择雄性新西兰大白兔30只,随机分为MSC组,VP组,稳定斑块(SP)组,每组10只。分别于细胞移植后3d、1周、2周采集兔血清,ELISA法检测血清高敏C反应蛋白(hs-CRP)、TNF-α、白细胞介素6(IL-6),白细胞介素10(IL-10)水平。10周末处死所有动物,取右侧颈总动脉分别行HE染色观察镜下病变,并测量纤维帽/脂核横截面厚度的比值。结果 SP组粥样硬化斑块形态结构完整,纤维帽较厚,斑块内炎性细胞较少,未见斑块破裂。VP组斑块中心可见大量脂核,表面覆盖较薄纤维帽,肩部可见残存泡沫细胞和大量炎性细胞浸润,部分斑块可见破裂和(或)血栓形成。MSC组形态介于之间。MSC组和SP组纤维帽/脂核比值明显高于VP组(P<0.01)。与VP组比较,MSC组各时间点hs-CRP、TNF-α和IL-6水平明显降低,IL-10水平明显升高(P<0.05,P<0.01);与SP组比较,MSC组和VP组各时间点hs-CRP、TNF-α、IL-6和IL-10水平明显升高(P<0.05,P<0.01)。结论 MSC可降低斑块不稳定性,其机制可能与降低机体炎性因子水平、增加抑炎因子及减轻炎性反应有关。

Objective To study the effect of intravenous bone mesenchymal stem cells （MSC） infu- sion on vulnerable plaques （VP） in atherosclerotic rabbits. Methods Thirty healthy male New Zealand white rabbits were randomly divided into MSC group, VP group, stable plaque （SP） group （10 in each group）. Serum was collected 3 days,1 and 2 weeks after MSC transplantation. Serum levels of hs-CRP, TNF-α, IL-6, IL-10 were measured by ELISA. The animals were sacrificed at week 10. Lesions in right common carotid were observed with HE staining. The fibroous cap/lipid core ratio of atherosclerotic plaques was calcultedd. Results The following were observed in VP group,including intact morphological structure of athroslerotic plaues, thick fibrous cap, a small number of inflammatory cells, no ruptured plaques, massive lipid cores in the center of plaques covered by thin fibrous cap, residual foam cells with infiltration of a large number of inflammatory cells in the shoulder with ruptured plaques and/or thrombosis. The fibrous cap/lipid core ratio of atherosclerotic plaques was higher in MSC group and SP group than in VP group （P〈0.01）. The serum levels of hs-CRP,TNF-α,and IL-6 were significantly lower whereas the serum IL-10 level was significantly higher in MSC group and SP group than in VP group at different time points （P〈0.05,P〈0. 01）. Conclusion MSC reduce unstable plaques by down-regulaing inflammatory reactions and up-regulating anti-inflammatory cytokine level.