Propofol dose-dependently reduces tumor necrosis factor-α-induced human umbilical vein endothelial cell apoptosis:: Effects on Bcl-2 and Bax expression and nitric oxide generation
Propofol dose-dependently reduces tumor necrosis factor-α-induced human umbilical vein endothelial cell apoptosis:: Effects on Bcl-2 and Bax expression and nitric oxide generation
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DOI：
10.1213/01.ane.0000150945.95254.d8
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发表时间：
2005-06-01
影响因子：
5.7
通讯作者：
Liu, XY
中科院分区：
文献类型：
--
作者：
Luo, T;Xia, ZY;Liu, XY
我们研究了异丙酚是否能抑制肿瘤坏死因子α诱导的人脐静脉内皮细胞的凋亡。分离的人脐静脉内皮细胞在添加20%小牛血清的Dulbecco‘s改良Eagle培养液中培养。未处理组和丙泊酚对照组HUVEC在37℃下培养24.5h，肿瘤坏死因子处理组的HUVECs最初分别加入肿瘤坏死因子或不同浓度的异丙酚培养30min，然后在培养液中加入40 ng/m L的肿瘤坏死因子培养24 h。用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法(TUNEL)检测细胞凋亡，并用电子显微镜证实。免疫细胞化学方法检测抗凋亡蛋白Bcl2和促凋亡蛋白Bax的表达。经肿瘤坏死因子刺激后，HUVECs中Bcl2/Bax比值降低，凋亡指数(AI：凋亡率)升高。丙泊酚浓度为12 mU/M时，可显著抑制肿瘤坏死因子诱导的心肌细胞AI升高和Bcl2/Bax比值降低(P<0.001)，且呈剂量依赖性。伴随而来的是一氧化氮产量的增加。Bcl2/Bax表达与AI呈负相关(P=0.0009)。这些结果表明，临床相关浓度的异丙酚可以减少肿瘤坏死因子诱导的HUVEC凋亡。免疫细胞化学方法检测抗凋亡蛋白Bcl2和促凋亡蛋白Bax的表达。经肿瘤坏死因子刺激后，HUVECs中Bcl2/Bax比值降低，凋亡指数(AI：凋亡率)升高。丙泊酚浓度为12mU/M时，可显著抑制肿瘤坏死因子诱导的心肌细胞AI升高和Bcl2/Bax比值降低(P<0.001)，且呈剂量依赖性。伴随而来的是一氧化氮产量的增加。Bcl2/Bax表达与AI呈负相关(P=0.0009)。这些结果表明，临床相关浓度的异丙酚可以减少肿瘤坏死因子诱导的HUVEC凋亡。
We investigated whether propofol can inhibit tumor necrosis factor (TNF)-alpha-induced apoptosis in cultured human umbilical vein endothelial cells (HUVECs). Isolated HUVECs were cultured in Dulbecco's modified Eagle medium supplemented with 20% bovine calf serum. HUVECs in untreated and propofol control groups were cultured at 37 degrees C for 24.5 h. HUVECs in the TNF treatment groups were initially cultured for 30 min in the presence of TNF or various concentrations of propofol, respectively, which were then cultured for 24 h with the addition of TNF at 40 ng/mL in the medium. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and confirmed by electron microscopy. The antiapoptotic Bcl-2 and proapoptotic Bax protein expressions were measured by immunocytochemical analysis. TNF stimulation resulted in a reduced Bcl-2/ Bax ratio and increased apoptotic index (AI: percentage of apoptotic cells) in HUVECs. Propofol, at concentrations >= 12 mu M, significantly (P < 0.001) and dose dependently attenuated TNF-induced increase in AI and decrease in Bcl-2/Bax ratio. This was accompanied by increases in nitric oxide production. There is an inverse correlation between the ratio of Bcl-2/Bax expression and AI (P = 0.0009). These results suggest that propofol, at clinical relevant concentrations, can reduce TNF-induced HUVEC apoptosis. The antiapoptotic Bcl-2 and proapoptotic Bax protein expressions were measured by immunocytochemical analysis. TNF stimulation resulted in a reduced Bcl-2/ Bax ratio and increased apoptotic index (AI: percentage of apoptotic cells) in HUVECs. Propofol, at concentrations 12 mu M, significantly (P < 0.001) and dosedependently attenuated TNF-induced increase in AI and decrease in Bcl-2/Bax ratio. This was accompanied by increases in nitric oxide production. There is an inverse correlation between the ratio of Bcl-2/Bax expression and AI (P = 0.0009). These results suggest that propofol, at clinical relevant concentrations, can reduce TNF-induced HUVEC apoptosis.