SDF-1通过PI3K/Akt和MAPK/Erk信号通路对人微血管内皮细胞功能产生影响  

SDF-1 affects human microvascular endothelial cell function by influence PI3K/Akt and MAPK/Erk signaling pathway

作　　者：高静[1] 朱红霞[1] 王敏哲[1] 苟静[1] 张丽[1] 

机构地区：[1]新疆医科大学第五附属医院内分泌科,新疆乌鲁木齐830011

出　　处：《南京医科大学学报（自然科学版）》2015年第9期1205-1210,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：新疆维吾尔自治区自然科学基金(2014211C129)

摘　　要：目的 :观察基质细胞衍生因子-1(stromal cell derived factor-1,SDF-1)对人微血管内皮细胞(human microvascular endothelial cell line-1,HMEC-1)功能的影响,并对相关机制进行初步探讨,从而明确SDF-1在糖尿病血管病变中的作用。方法:体外培养HMEC-1,分别在培养基中加入不同浓度的SDF-1(0、25、50、100μg/L),Western blot检测HMEC-1中PI3K/Akt和MAPK/Erk信号通路的活化情况,MTT和流式细胞分析检测HMEC-1增殖和凋亡能力的变化情况,划痕愈合实验检测HMEC-1迁移能力的变化情况。采用PI3K/Akt和MAPK/Erk信号通路抑制剂LY294002和U0126阻断HMEC-1中PI3K/Akt和MAPK/Erk信号通路后,再以SDF-1处理HMEC-1,MTT和流式细胞分析检测HMEC-1增殖和凋亡能力的变化情况;划痕愈合实验检测HMEC-1迁移能力的变化情况。结果:Western blot结果显示,25μg/L的SDF-1处理即可显著活化HMEC-1中的PI3K/Akt和MAPK/Erk信号通路,且随着SDF-1处理浓度的升高,PI3K/Akt和MAPK/Erk信号通路活化水平逐渐升高。同0μg/L的SDF-1处理组相比,25、50、100μg/L的SDF-1均可显著加强HMEC-1的增殖和迁移能力(P<0.01),并抑制HMEC-1的凋亡水平(P<0.01),且这种作用具有剂量依赖性。当采用LY294002和U0126阻断HMEC-1中的PI3K/Akt和MAPK/Erk信号通路后,SDF-1促HMEC-1增殖和迁移能力及抑制HMEC-1凋亡的能力均显著降低(P<0.01)。结论:SDF-1可通过活化PI3K/Akt和MAPK/Erk信号通路,进而促进HMEC-1的增殖和迁移,并抑制HMEC-1的凋亡水平,从而在糖尿病血管病变中发挥一定的作用。Objective：To observe the effect of stromal cell derived factor-1（SDF-1）on human microvascular endothelial cell line-1（HMEC-1）,and study the relevant mechanism. Methods：HMEC-1 cells were treated with SDF-1 of different concentrations（0,25,50,100 μg / L）,then the phosphorylation level of PI3 K / Akt and MAPK / Erk were detected by Western blot,and the proliferation ability and apoptosis rate of HMEC-1 cells were detected by MTT and FCM. Changes on migration ability of HMEC-1cells was detected by wound healing assay. MCF-7 cells were pretreated with PI3 K / Akt and MAPK / Erk signaling pathway inhibitor to observe the effect of PI3 K / Akt and MAPK / Erk signaling pathway on SDF-1 induced proliferation,apoptosis and migration in HMEC-1 cells. Results：Compared with 0 μg / L SDF-1 treated group,25,50 and 100 μg / L SDF-1 treatment actived PI3 K / Akt and MAPK / Erk signaling pathway,promoted proliferation and migration ability,and induced HMEC-1 cells apoptosis（P〈0.01）,and those effects were concentration-dependent. When pretreated with PI3 K / Akt and MAPK / Erk signaling pathway inhibitor,the effect of SDF-1 on promoting proliferation and migration ability,and inducing HMEC-1 cells apoptosis ability were significantly blocked. Conclusion：By activation PI3 K / Akt and MAPK / Erk signaling pathway,SDF-1 can promote proliferation and migration ability,and induce HMEC-1cells apoptosis,thus plays a role in diabetic angiopathy.

关 键 词：基质细胞衍生因子-1 信号通路 糖尿病 人微血管内皮细胞 PI3K/AKT MAPK/ERK 

分 类 号：R587.1[医药卫生—内分泌]