金雀异黄酮、波生坦、他达拉非治疗野百合碱诱导的大鼠肺动脉高压疗效的比较

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目的比较金雀异黄酮、波生坦、他达拉非治疗野百合碱诱导大鼠肺动脉高压的疗效。方法 SD大鼠一次性腹腔注射野百合碱(50mg/kg)诱导肺动脉高压模型(n=48),对照组大鼠(n=8)给予腹腔注射生理盐水。3周成功建模后分为肺动脉高压组(生理盐水灌胃)、金雀异黄酮不同剂量组[G30、G60、G120组,分别给予金雀异黄酮30、60、120mg/(kg·d)剂量灌胃]、波生坦组[波生坦5mg/(kg·d)灌胃]、他达拉非组[他达拉非0.5mg/(kg·d)灌胃],每组8只。对照组大鼠予以生理盐水灌胃。干预2周后,比较各组生存率、右房室瓣反流速度、肺动脉内径、平均肺动脉压力、血管舒张功能、右心室肥厚指数、肺组织病理情况。结果与对照组相比,肺动脉高压组大鼠右房室瓣反流速度增快,肺动脉内径增宽,平均肺动脉压升高、右心室肥厚指数升高,差异均有统计学意义(P<0.05)。而与肺动脉高压组相比,金雀异黄酮能降低野百合碱诱导的肺动脉高压大鼠的右房室瓣反流速度(G60、G120)、肺动脉内径(G120)、平均肺动脉压(G30、G60、G120)、右心室肥厚指数(G60、G120),提高大鼠生存率(G120)及内皮依赖性舒张功能(G30、G60、G120),改善肺血管管腔狭窄、管壁增厚、血管平滑肌细胞增殖(G30、G60、G120),差异均有统计学意义(P<0.05),但上述作用均次于波生坦、他达拉非组(P<0.05)。结论金雀异黄酮对野百合碱诱导的大鼠肺动脉高压有一定治疗效果,虽其疗效不及波生坦、他达拉非,但金雀异黄酮价格低廉、容易获得、不良反应少,有望成为治疗肺动脉高压的新型辅助药物。 Objective To compare the curative effect of genistein, bosentan and tadalafil on monocrotaline-induced pulmonary hypertension in rats. Methods SD rats were injected intraperitoneally with monocrotaline (50mg / kg) to induce pulmonary hypertension (n = 48), and control rats (n = 8) were injected intraperitoneally with saline. After 3 weeks of successful modeling, the rats were divided into three groups: pulmonary hypertension group (normal saline group), genistein group (G30, G60, G120 group), genistein 30,60,120mg / (kg · d) Dose gavage], bosentan group [bosentan 5mg / (kg · d) gavage], tadalafil group [tadalafil 0.5mg / (kg · d) gavage], each group of 8 . Rats in control group were given normal saline. Two weeks after the intervention, survival rate, right atrioventricular valve regurgitation velocity, pulmonary artery diameter, mean pulmonary artery pressure, vasodilation, right ventricular hypertrophy index and pathological changes of lung tissue were compared. Results Compared with the control group, pulmonary hypertension in the right ventricular valve regurgitation faster, pulmonary artery diameter widening, mean pulmonary hypertension, right ventricular hypertrophy index increased, the difference was statistically significant (P <0.05 ). Compared with the pulmonary hypertension group, genistein could reduce the RVF-induced right atrial valve regurgitation (G60, G120), pulmonary artery diameter (G120), mean pulmonary artery pressure (G30, G60 , G120), right ventricular hypertrophy index (G60, G120), increase of rat survival rate (G120) and endothelium-dependent diastolic function (G30, G60, G120), improve pulmonary vascular stenosis, wall thickening, vascular smooth muscle The cell proliferation (G30, G60, G120) was significantly different between the two groups (P <0.05). However, the above effects were all secondary to bosentan and tadalafil (P <0.05). Conclusions Genistein may have a therapeutic effect on monocrotaline-induced pulmonary hypertension in rats. Although its efficacy is less than that of bosentan and tadalafil, genistein is inexpensive, readily available and has few side effects and is expected to become New Auxiliary Drugs for Pulmonary Hypertension.
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