3TSR体内外诱导内皮细胞凋亡的研究  

Induction of apoptosis of vascular endothelial cells by 3TSR in vitro and in vivo

作　　者：金洲祥[1] 朱少俊[1] 张雪峰[2] 徐鲁白[1] 王继生[1] 

机构地区：[1]温州医学院附属第二医院普通外科,325027 [2]美国哈佛医学院Beth Isreal Deaconess 医学中心外科系

出　　处：《中华实验外科杂志》2007年第5期585-587,642,共4页Chinese Journal of Experimental Surgery

基　　金：浙江省教育厅自然科学基金(20051188)

摘　　要：目的观察血管形成抑制剂3TSR体内外对内皮细胞的影响,并探讨与细胞凋亡蛋白酶-3(Caspase-3)的关系。方法在体外培养条件下比较对照组、不同剂量3TSR(1～3μmol/L)作用48h对人脐静脉血管内皮细胞增殖及凋亡的影响,并用逆转录-聚合酶链反应(RT-PCR)法检测各组Caspase-3 mRNA转录水平。建立裸鼠原位胰腺癌模型,进行随机干预实验,比较对照组(每日0.2ml生理盐水腹腔注射)、3TSR1组(每日1mg/kg体重腹腔注射)、3TSR2组(每日2mg/kg体重腹腔注射)及3TSR3组(每日3mg/kg体重腹腔注射),每组6只,3周后检测胰腺癌原位肿瘤血管内皮细胞凋亡率。结果体外培养时3TSR对人脐静脉内皮细胞有显著增殖抑制及凋亡诱导作用,作用48h后其凋亡率分别为(10.3±3.2)%,(12.4±4.1)%和(20.1±5.4)%,均显著高于对照组(P<0.05)。3TSR1组、3TSR2组和3TSR3组Caspase-3 mRNA转录水平相对强度分别(0.76±0.11),(0.79±0.21)和(0.89±0.19),均显著高于对照组(P<0.05),且随浓度增加而增强。体内实验时3TSR能显著诱导胰腺癌血管内皮细胞凋亡,3TSR1组、3TSR2组及3TSR3组凋亡率分别为(7.8±3.0)%,(14.6±4.9)%和(15.9±3.2)%,均显著高于对照组(P<0.05)。结论3TSR体内外均能诱导内皮细胞的凋亡,且呈一定的浓度依赖性,其作用机制可能与促进Caspase-3基因转录有关。Objective To investigate the effects of angiogenie inhibitor 3TSR on vascular endothelial cells in vitro and in invo, and explore its relationship with the expression of Caspase-3 mRNA. Methods Methyl thiazolyl tetrazolium method （MTT） and Annexin V-FITC method were used to detect the cell growth and apoptesis rate of human umbilical vein endothelial cells （HUVEC） after treatment with 3TSR at different dosages （1-3μmoL/L）. The expression of Caspase-3 mRNA was detected by RT-PCR. Human pancreatic carcinoma cells were inoculated in pancreas of immunodefieieney mice, and then the mice were divided into 4 groups：control group,3TSR1 （1 mg/kg） group,3TSR2 （2 mg/kg） group and 3TSR3 （3 mg/kg） group, with 6 mice each group. The apoptosis rate of VECs treated with 3TSR for 3 weeks was detected. Results 3TSR inhibited the proliferation of HUVECs in a concentration-dependent manner. The apoptosis rates in 3TSR-treated groups after treatment for 48 h were （10.3 ± 3.2）%, （12.4 ±4.1）% and （20.1 ±5.4）% ,respectively,significantly higher than those in control group （P〈 0.05 ）. The relative values of the expression of Caspase-3 mRNA in treated groups were （ 0.76 ± 0.11 ）, （0.79 ± 0.21 ） and （0.89 ± 0.19 ）, respectively, significantly higher than in control group. In vivo the apoptosis rates of VECs in 3TSR1 group,3TSR2 group and 3TSR3 group were （7.8 ± 3.0）%, （14.6 ± 4.9） % and （15.9 ± 3.2）%, respectively, significantly higher than in control group. Conclusion 3TSR may inhibit the proliferation and induce apoptesis of VECs in vitro and in vivo, the mechanisms of which may be related to the elevated expression of Caspase-3 mRNA.

关 键 词：内皮细胞 胰腺细胞 脱噬作用 增殖 

分 类 号：R735.9[医药卫生—肿瘤]