The Experiment Study Of The Homocysteine Effect On Endothelial Dysfunction And Clinical Observation On Protection Of The Composite Dan Shen Pills On Endothelial Dysfunction

Vascular endothelial dysfunction is one of the most sensitive indicators for atherosclerosis, which displays prior to the changes of vascular morphology. Hyperhomocysteinemia is a new independent risk factor for cardiovascular disease, but the mechanism of the vascular injury seen in hyperhomocysteinemia is unknown. This study investigated its mechanism in endothelial dysfunction by establishing animal model of hyperhomochysteinemia. Compound danshen dripping pills could obviously decrease the reoccurance and mortality rate of cardiac attack. However there was no report on the effect of the compound danshen dripping pills on vascular endothelial function. This study is to investigate the mechanism of vascular endothelial dysfunction from basic and clinical point of view and to evaluate the significance of early intervention on vascular endothelial dysfunction in prevention and cure of coronary artery disease.Objectives: 1. Through observation of the changes of NO ET and activity ofGSH-PX> VCAM-1 in plasma of HHCY rabbits to study the effects of oxidant stress in endothelial dysfunction; 2. To evaluate the effect of antioxidant ascorbic acid(Vitc) in protecting hyperhomochysteinemia-induced endothelial dysfunction in rabbits; 3. To observe effect of the compound Dan shen dripping pills on vascular endothelium functionMaterials and methods: 1. Experiment one: Eighteen rabbits were randomized into two groups (n=9 per group), methionine group (M group) were poured L-methionine (3.3g/kg weight)into stamach. NO. ET and activity of GSH-PX. sVCAM-1 in plasma were examined at 0. 4. 8. 12. 24hour,at same time, EDD. EID were detected by high resolution ultrasound and external ilial arteries were observed by trandelectron microscope after 24 hours; 2. Experiment two: Rabbits were randomized into three groups (N=9 per group), normal control group (N group)received normal diet, methionine group(M group)received methionine-rich diet consisted of L-methioine 0.8g/kg weight day, methionine+Vitc group (MC group) received diet consisted of L-methioine 0.8g/kg weight day and Vitc 1.0g/kg weight day. Then NO, ET and activity of GSH-PX. sVCAM-1 in plasma were examined at 20. 40. 60. 80day. At same time EID. EDD were examined by transmission eleciron microscope(HRUS) after 80days; 3. Experiment three: 60 patients associating with CAD risk factors in our study. They were randomly divided into two groups, Control group(n=30)who don't use any drug, treatment group(n=30) took composite Dan Shen pill 20-pill, twice every day, for sixmonths. With high-resolution ultrasound examine EDD. EID of the brachial artery at Oday. 30day. 90day. 180day.Results 1. The changes of EDD in acute hyperhomocysteinemia. EDD of external iliac artery in M group was time-dependent reduced significantly(Ohour, 13.98+1.96%; 4hour, 3.50+1.61%; 8hour, -1.53+3.01%; 12hour, -2.49+1.83%; 24hour, -5.03+ 1.62%), compared with that in control group; but EID was not affected. 2. Biochemical changes in acute hyperhomocysteinemia (1) NO in plasma: NO in plasma of M group was reduced significantly than that of control group (N group: 208.3 l+22.45umol/L vs M group Ohour. 183.56+38.10 umol/L: 4hour: 127.13+21.23 umol/L: 8hour: 115.29+10.04 umol/L; 12hour: 102.24+15.01 umol/L; 24hour: 97.35+31.12umol/L);(2)ETin plasma: ET in plasma of M group rabbits was increased significantly (N group: 174.12+24.15pg/ml vs M group : Ohour: 190.37+46.28 pg/ml ; 4hour: 258.42+71.36 pg/ml; 8hour: 368.43+51.27 pg/ml; 12hour: 447.39+37.21 pg/ml; 24hour: 399.29+41.37 pg/ml: P<0.01). (3) Changes of GSH-PX and sVCAM-1: There was no difference in GSH-PX sVCAM-1 between M and N group. 3. Endothelian function changes in chronic hyperhomocysteinemia: EDD decreased significantly in both MC and M groups with time and EID began to decrease 60 days later. After 80 days, EDD of external iliac arteries in MC group and M group was 2.77+3.46% and -6.46+1.33% and reduced significantly compered with mat in N group (13.10+2.45%, p<0.01). EDD in M group reduced significantly than that in MC group, while...