利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其机制研究

发布时间：2019-05-05 15:39

【摘要】：目的:研究利拉鲁肽对离体大鼠胸主动脉环的血管舒张效应及其作用机制。方法:分离32只SD雄性大鼠的胸主动脉环,分成去内皮组(n=16)和内皮完整组(n=16)。采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察利拉鲁肽(1×10-5 mol/L)对去甲肾上腺素(1×10-6 mol/L)预收缩的胸主动脉环的舒张作用。随后内皮完整组又分为左旋硝基精氨酸甲酯干预亚组(n=8)和格列苯脲干预亚组(n=8),分别接受一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(1×10-4 mol/L)和非特异性ATP敏感性钾通道(KATP)抑制剂格列苯脲(1×10-5 mol/L)的预处理,预处理后利拉鲁肽分别作用于预处理过的去甲肾上腺素预收缩的胸主动脉环,观察利拉鲁肽对离体大鼠胸主动脉环作用的影响。结果:利拉鲁肽对基础状态的胸主动脉环无作用。去甲肾上腺素预收缩胸主动脉环后,当利拉鲁肽浓度达到1×10-5 mol/L时,利拉鲁肽对去内皮组和内皮完整组胸主动脉环均有舒张作用,但对内皮完整组舒张作用更强,胸主动脉环最大舒张幅度达17%(P0.05),差异有统计学意义。经左旋硝基精氨酸甲酯和格列苯脲预处理后,左旋硝基精氨酸甲酯干预亚组利拉鲁肽对胸主动脉环舒张幅度为4%(P0.05),与预处理前相比差异有统计学意义。格列苯脲干预亚组利拉鲁肽对胸主动脉环舒张幅度为14%(P0.05),与预处理前相比差异无统计学意义。结论:利拉鲁肽对去甲肾上腺素预收缩的胸主动脉环有明显的舒张作用,其机制与内皮细胞一氧化氮合酶有关。而KATP未能阻断利拉鲁肽的血管舒张作用。
[Abstract]:Aim: to study the vasodilation effect of Lilarupeptide on isolated rat thoracic aortic rings and its mechanism. Methods: the thoracic aortic rings of 32 male SD rats were isolated and divided into two groups: endothelium-free group (n = 16) and endothelium-intact group (n = 16). The changes of tension of vascular rings were measured by biological signal acquisition and analysis system in vitro. The vasodilation of noradrenaline (1 脳 10 ~ 6 mol/L) precontracted thoracic aortic rings was observed in rats with Lilaruin (1 脳 10 脳 10 ~ 5 mol/L). Then the endothelium intact group was divided into L-nitro-arginine methyl ester intervention subgroup (n = 8) and glibenclamide intervention subgroup (n = 8). They were pretreated with nitric oxide synthase inhibitor L-nitro-arginine methyl ester (1 脳 10 渭 4 mol/L) and non-specific ATP-sensitive potassium channel (KATP) inhibitor glibenclamide (1 脳 10 渭 5 mol/L), respectively. The preconditioned thoracic aortic rings precontracted by noradrenalin were treated with Lilalu peptide, and the effects of Lilaruin on isolated rat thoracic aortic rings were observed. Results: Lilarutide had no effect on the basic thoracic aortic rings. After noradrenalin precontracted the thoracic aortic rings, when the concentration of Lilaruin reached 1 脳 10? 5 mol/L, Lilalu peptide had a relaxing effect on the thoracic aortic rings in both endothelium-free and endothelium-intact groups, but it was stronger in the endothelium-intact group than that in the endothelium-intact group, but the vasodilation effect was stronger in the endothelium-intact group than that in the control group. The maximal relaxation amplitude of thoracic aortic rings was 17% (P0.05), the difference was statistically significant. After pretreatment with L-nitro-arginine methyl ester and glibenclamide, the relaxation amplitude of L-nitro-L-arginine methyl ester on thoracic aortic rings was 4% (P0.05), which was significantly different from that before pretreatment. The relaxation amplitude of glibenclamide on thoracic aortic rings was 14% (P0.05), and there was no significant difference compared with pre-pretreatment. Conclusion: Lilarutide has an obvious relaxation effect on noradrenaline-precontracted thoracic aortic rings, and its mechanism is related to endothelial nitric oxide synthase. However, KATP failed to block the vasodilation effect of LilaluPeptide.
【作者单位】：山西医科大学第一临床医院心血管内科;
【基金】：山西省回国留学人员科研资助项目(项目编号2012-050)
【分类号】：R965

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