HO通过减少ROS生成抑制AngⅡ的致血管平滑肌细胞增殖肥大  

Heme oxygenase decreases the generation of ROS in AngⅡ induced proliferation and hypertrophy of cultured vascular smooth muscle cells

作　　者：庞东卫[1] 韩莉[2] 刘洁[2] 马铁民[2] 徐海[2] 

机构地区：[1]包头医学院生理教研室,内蒙古包头014010 [2]北京大学医学部生理与病理生理学系,北京100083

出　　处：《中国病理生理杂志》2009年第3期476-479,共4页Chinese Journal of Pathophysiology

摘　　要：目的:观察血红素加氧酶(HO)在AngⅡ致血管平滑肌细胞(VSMCs)增殖和肥大中的作用并探讨其可能机制。方法:(1)免疫印迹法测定平滑肌细胞HO-1蛋白表达水平;(2)β-液体闪烁记数仪测定[3H]-TdR和[3H]-亮氨酸掺入量;(3)乙酰乙酸双氯荧光素(DCFH-DA)法测定平滑肌细胞内活性氧(ROS)水平。结果:(1)Hemin组HO-1蛋白表达水平与对照组和AngⅡ组相比均明显升高(P<0.01)。(2)AngⅡ使血管平滑肌细胞[3H]-TdR和[3H]-亮氨酸掺入量较对照组分别升高20.7%和18.0%(P<0.01),而给予HO底物Hemin则抑制了[3H]-TdR和[3H]-亮氨酸掺入量的增加,给予HO的抑制剂ZnPPIX则可以促进AngⅡ所致的[3H]-TdR、[3H]-亮氨酸掺入量的增加。(3)AngⅡ组ROS水平明显高于对照组(P<0.01);Hemin组ROS水平较AngⅡ组降低了62.7%,而ZnPPIX组高于AngⅡ组39.5%。结论:HO可抑制AngⅡ所导致的VSMCs的增殖和肥大,其机制可能与减少细胞内ROS生成有关。AIM： To investigate the role of heme oxygenase （HO） in Ang Ⅱ induced proliferation and hypertrophy of cultured vascular smooth muscle cells. METHODS ： （ 1 ） Western blotting analysis was carried out to detect protein level of HO- 1 in the tissues. （2） [3H] -TdR, [3H] -leucine incorporation was measured in cultured vascular smooth muscle cells. （3） 2＇,7＇ -dichlorofluorescin diacetate （DCFH -DA） as an index was used to determine the cellular reactive oxygen species （ROS） level. RESULTS： （1） No significant difference in HO - 1 protein expression level between Ang Ⅱ - stimulated and control groups was observed, but HO - 1 protein level in Hemin - induced group was higher than that in other two groups （P 〈0. 01 ）. No significant increase in HO - 1 protein expression was found in zinc - protoporphyrin IX （ZnPPIX） group. （2） After Ang Ⅱ stimulation, [ 3 H ] - TdR and [ 3 H ] - leucine incorporations of vascular smooth muscle cells （VSMCs） were increased. Hemin inhibited this increase. The higher concentration of Heroin, the more significant was the inhibitory effect. On the contrary, ZnPPIX promoted the increase in the effect of Ang Ⅱ by inhibiting HO. （3） Fluorescence intensity in AngⅡ group was obviously higher than that in control groups （ P 〈 0. 01 ）. Compared with Ang Ⅱ group, Heroin group decreased 62. 7%, but ZnPPIX group increased 39. 5%. CONCLUSION： Hemin induces HO - 1 expression and inhibits the effect of Ang Ⅱ to stimulate proliferation and hypertrophy of VSMCs. The mechanism may be related to its inhibition of ROS production.

关 键 词：血红素加氧酶 活性氧 血管紧张素Ⅱ 血管平滑肌细胞 

分 类 号：R363[医药卫生—病理学]