摘要
目的:研究脑心通对氧化低密度脂蛋白(ox-LDL)损伤血管内皮的保护作用及其分子机制.方法:在建立人脐静脉内皮细胞(HUVEC)ox-LDL(50mg/L)损伤模型的基础上,以阿托伐他汀(1μmol/L)作为阳性对照,并给予0.2,0.4,0.6,0.8g/kg不同剂量脑心通含药血清预先干预.采用硝酸还原酶法、放免法、分光光度计比色法、流式细胞技术等检测HUVECNO,ET-1,LDH释放量,细胞内Caspase-3活性和早期凋亡率.结果:HUVEC损伤后,ox-LDL组(4.74±1.61)μmol/L与对照组(9.96±1.57)μmol/L相比较,NO的合成显著减少,而ET-1释放明显增加[(44.72±2.01)ng/Lvs(21.42±2.84)ng/L,P<0.01].与ox-LDL组(4.74±1.61)μmol/L相比较,ox-LDL+脑心通0.2,0.4,0.6,0.8g/kg组[(8.33±1.78),(11.35±2.14),(14.80±2.40),(17.82±2.02)μmol/L,P<0.05)]呈剂量依赖性,并可促进NO合成,但对ET-1释放无明显影响.而ox-LDL+阿托伐他汀组不仅可以促进NO合成,且能抑制ET-1释放(P<0.01);ox-LDL可显著提高HUVEC的Caspase-3酶活性,促进LDH释放(P<0.05),与ox-LDL组比较,ox-LDL+脑心通组对此呈剂量依赖性抑制作用[(193.00±16.81)μmol/Lvs(168.00±11.51),(135.00±11.18),(117.00±10.37),(99.00±9.62)μmol/L,P<0.05],[(470.28±23.34)μmol/Lvs412.14±25.67),(311.37±28.34),(294.57±20.22),(276.49±25.32)μmol/L,P<0.05],但阿托伐他汀对LDH释放无明显影响.脑心通、阿托伐他汀均能明显抑制ox-LDL诱导的内皮细胞凋亡(P<0.01).结论:中药脑心通可促进内皮细胞NO释放,减轻内皮细胞的损伤与凋亡,是其保护血管内皮的可能机制.
AIM： To investigate the protective effect of NaoXin- Tong（NXT） on vascular endothelial cell （ HUVEC ） from injury induced by ox-LDL and the possibly molecular mechanism. METHODS ： ox-LDL of 50 mg/L was used and co-incubated with HUVECs to establish injured model of HUVEC. Atorvastatin （1μmol/L）was used as positive control and different doses （0.2, 0.4, 0.6 and 0.8 g）of NXT containing serum were used to intervene in advance. The contents of NO, ET-1 and LDH in the supernatant of HUVEC, the activity of intracellular Caspase-3 and the apoptosis of the HUVEC were examined by enzyme method, radio-immune method and Flow cytometry. RESULTS： Compared with those in normal control group, the contents of NO in the supernatant of ox-LDL-injured HUVECs significantly decreased [ （9.96 ± 1.57） μmol/L vs （4.74 ± 1.61 ） μmol/L） ], whereas the secretion of ET-1 significantly increased [ （ 21.42 ± 2.84） ng/L vs （44.72 ±2.01） ng/L, P 〈0, 05]. Compared with those in ox-LDL group, NXT promoted the contents of NO of ox-LDL-injured HUVECs in a dose dependent manner [ （ 8.33 ± 1.78）, （11.35 ±2.14）, （14.80 ±2.40）, （17.82 ±2.02） txmol/L vs （4.74 ± 1.61 ） μmol/L, P 〈0.05] , but the secretion of ET-1 was not affected. Atorvastatin not only promoted the release of NO of HUVECs but also inhibited the secretion of ET-1 （P 〈0.01 ）. The activity of intracellular Caspase-3 and the contents of LDH in the supernatant of ox-LDL-injured HUVEC significantly increased and NXT inhibited the effect in a dose dependent manner [（193.00 ± 16. 81） μmol/L vs （168.00 ± 11.51）, （135.00 ±11.18）, （117.00±10.37）, （99.00 ±9.62） μmol/L, P 〈 0. 05 ], [ （470.28 ± 23.34 ） μmol/L vs （412.14 ± 25.67 ）, （311.37 ± 28.34）, （294.57 ± 20.22）, （276.49 ± 25. 32）μmol/L, P 〈 0.05 ]. But atorvastatin had no effect on the release of LDH of HUVECs. NXT and atorvastatin both significantly inhibited the apoptosis of the ox-LDL-induced HUVECs （P
出处
《第四军医大学学报》
CAS
北大核心
2009年第9期856-859,共4页
Journal of the Fourth Military Medical University
关键词
脑心通
血管内皮细胞
氧化低密度脂蛋白
一氧化氮
内皮素-1
乳酸脱氢酶
CASPASE-3
调亡
NaoXinTong（NXT）
human umbilical vascular endothelial cells （ HUVEC ）
ox-LDL
nitric oxide（NO）
endothelin-1 （ET-1）
Lactate dehydrogenase（LDH）
Caspase-3
apoptosis
