Protective Effect Of Clopidogrel On Nicotine Induced Endothelial Dysfunction In Rats

Objective To reseach the protective effect of clopidogrel on nicotine - induced endothelial dysfunction in rats.Methods 40 SD rats, Weight 180～220g, were divided into five groups:①normal control group,②nicotine control group (2 mg / kg),③low-dose clopidogrel group (nicotine 2 mg / kg + clopidogrel 3mg/kg),④middle dose clopidogrel group (nicotine 2 mg / kg + clopidogrel 10mg/kg),⑤high-dose clopidogrel group (nicotine 2 mg / kg + clopidogrel 30mg/kg). The day before and 4 weeks later of modeling, sublingual vein blood,to measure plasma SOD, ET-1 and NO levels of the rats. After the test , take each group of rat thoracic aorta to Make of paraffin sections, SABC immunohistochemical staining method ,to observed the expression of eNOS In vascular endothelial cells under light microscope . We observe the morphological changes of vascular endothelial cells by the scanning electron microscopy.Results (1) The plasma SOD levels of model group were obviously lower than the control group (p <0.01),the plasma SOD levels of three-dose treatment group were obviously higher than the model group 4 weeks after modeling(p <0.01); the plasma SOD levels of model group were obviously lower than the the pre-modeling (p <0.01); the plasma SOD levels of low,middle dose group were obviously lower than the the pre-modeling (p <0.05, p <0.01); the plasma SOD levels of high-dose group were similar to the pre-modeling(p >0.05).(2) The plasma NO levels of model group were obviously lower than the control group (p <0.01),the plasma NO levels of three-dose treatment group were obviously higher than the model group 4 weeks after modeling(p <0.05, p <0.01); the plasma NO levels of model group were obviously lower than the the pre-modeling (p <0.01); the plasma NO levels of low,middle dose group were obviously lower than the the pre-modeling (p <0.05, p <0.01); the plasma NO levels of high-dose group were similar to the pre-modeling(p >0.05). (3) The plasma ET-1 levels of model group were obviously higher lower than the control group (p <0.01),the plasma ET-1 levels of middle,high dose treatment group were obviously lower than the model group 4 weeks after modeling(p <0.05, p <0.01); the plasma ET-1 levels of model group were obviously higher than the the pre-modeling (p <0.01); the plasma ET-1 levels of three-dose treatment group were obviously higher than the the pre-modeling (p <0.05, p <0.01).(4)The eNOS immunohistochemistry shows the eNOS positive of endothelial cells expression of the control group were(86.50±5.42%). The eNOS positive of endothelial cells expression of the model group (32.75±7.086%) were lower than the control group (p < 0.01). low-dose treatment group(39.50±6.02%) were higher than the model group (p <0.05). compared with model group ,the eNOS positive of endothelial cells expression of middle and high dose group ( 49.00±5.95%), (70.25±6.62%) were significantly higher (p <0.01).(5)SEM : the thoracic aortic endothelial apparent injury in the model group. Compared with the model group, the thoracic aorta endothelial damage of three-dose treatment group were mitigation.Conclusion Clopidogrel can significantly relieve the nicotine on vascular endothelial cell damage.