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目的动态观察普伐他汀治疗前后血小板源一氧化氮(NO)系统的变化及其与动脉粥样硬化(atherosclerosis,AS)进程的关系。方法高胆固醇饲养诱导AS新西兰白兔模型30只。设普伐他汀药物干预组(A组,0周时开始服用普伐他汀10mg/d至24周)、普伐他汀药物治疗组(B组,在高胆固醇饲养(12周时开始服用普伐他汀10mg/d至24周)、无药物对照组(C组,0~24周均不用药)。采用RT-PCR方法检测A、B、C三组在0,6,12,18,24周不同时间血小板源内皮型氧化氮合酶(eNOS)基因mRNA和诱导型氧化氮合酶(iNOS)基因mRNA表达、氧化氮合酶(NOS)活性及NO含量的变化;通过大体病理形态证实不同时间大动脉AS程度及斑块形成情况。结果血小板源eNOSmRNA在0,6,12,18,24周时的表达量:A组无明显改变;B组分别是0.95±0.77,0.53±0.33,0.49±0.25,0.83±0.28,1.00±0.77(P<0.05);C组分别是0.82±0.16,0.40±0.29,0.33±0.29,0.51±0.23,0.19±0.12(P<0.05)。6,12周时B组和C组与A组比较明显降低(P<0.05);18,24周时,B组与A组无明显差异,但A组和B组较C组明显增高(P<0.01)。iNOS mRNA表达在A、B、C三组不同时期均无变化。NOS活性及NO含量在三组不同时期变化与eNOS mRNA相似。大体形态:A组未见AS形成;B组12周时见大动脉内膜粗糙,有大量脂纹,24周时有部分大动脉仍有脂纹,但内膜较光滑,未见斑块;C组24周时各大动脉均见大量斑块或脂纹。结论随着高胆固醇血症(HC)及AS的形成,血小板源eNOS mRNA表达量、NOS活性及NO含量逐渐降低;普伐他汀能上调血小板源eNOSmRNA表达,提高NOS活性,并能稳定AS病变的继续发展或使其逆转。
Objective To observe the change of platelet-derived nitric oxide (NO) system and its relationship with atherosclerosis (AS) before and after pravastatin treatment. Methods Cholesterol-fed AS-induced New Zealand white rabbits model 30. Pravastatin treatment group (group A, pravastatin 10 mg / d to 24 weeks at 0 weeks), pravastatin treatment group (group B, pravastatin administration at 12 weeks 10mg / d to 24 weeks), no drug control group (C group, 0-24 weeks were not medication.) RT-PCR method to detect A, B, C three groups at 0,6,12,18,24 weeks are different Time of platelet-derived endothelial nitric oxide synthase (eNOS) mRNA and iNOS gene mRNA expression, nitric oxide synthase (NOS) activity and NO content changes; confirmed by gross pathology at different time aortic AS level and plaque formation.Results The expressions of platelet-derived eNOS mRNA at 0, 6, 12, 18 and 24 weeks: no significant change in group A, 0.95 ± 0.77, 0.53 ± 0.33 and 0.49 ± 0.25 in group B, 0.83 ± 0.28 and 1.00 ± 0.77 respectively (P <0.05), while those in group C were 0.82 ± 0.16,0.40 ± 0.29,0.33 ± 0.29,0.51 ± 0.23,0.19 ± 0.12 (P <0.05) There was no significant difference between group A and group B at 18 and 24 weeks (P <0.05), but the level of iNOS mRNA in group A and group B was significantly higher than that of group C (P <0.01) There was no change in A, B and C groups at different time points, and NOS activity and NO content were in three The changes in different periods were similar to those of eNOS mRNA. The general morphology: no AS formation was found in group A; the aortic intima was found to be rough at 12 weeks in group B, with a large number of lipid streaks; some of the major arteries still had lipid streaks at 24 weeks, , No plaques were found.At the 24th week in group C, a large number of plaques or lipid streaks were observed in all arteries.Conclusion With the development of hypercholesterolemia (HC) and AS, the eNOS mRNA expression, NOS activity and NO content gradually increased Reduce pravastatin can upregulate eNOS mRNA expression of platelet, increase NOS activity, and can stabilize the progression of AS lesions or to reverse.