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目的观察全反式维甲酸(ATRA)对阻力血管的舒张效应并探讨其相关机制。方法采用离体微血管张力测定系统,取健康雄性SpragueDawley(SD)大鼠肠系膜动脉随机分为:内皮完整ATRA处理组(n=8)、内皮去除后ATRA处理组(n=5)以及溶剂对照组(n=8),观察ATRA(1×10-8至3×10-6mol/L)对苯肾上腺素(PE,1×10-5mol/L)预收缩血管的影响。分别以左旋单甲基精氨酸(l-NMMA,1×10-5mol/L,n=4)、可溶性鸟苷酸环化酶(sGC)特异性拮抗剂(ODQ,1×10-5mol/L,n=5)及钾离子通道拮抗剂[4氨基吡啶(1×10-4mol/L)、格列苯脲(1×10-5mol/L)、蜂毒明肽+蝎毒素(1×10-5mol/L),n=6]孵育血管环30min,观察ATRA对血管的反应以进一步探讨其作用机制。结果在内皮完整肠系膜动脉上,ATRA呈浓度依赖性地降低PE(1×10-5mol/L)预收缩的肠系膜动脉环的张力;与内皮完整ATRA处理组比较,去内皮后ATRA最大舒张效应明显减弱[(17.1±6.7)%比(65.5±10.9)%,P<0.05]。l-NMMA、ODQ或蜂毒明肽+蝎毒素孵育后明显降低ATRA的舒血管作用,而4氨基吡啶和格列苯脲对ATRA舒血管作用影响不大。结论 ATRA能舒张由PE引起的血管收缩。其舒张机制可能是通过血管内皮细胞产生一氧化氮,进而活化下游的sGC,促使环磷酸鸟苷合成增加而激活平滑肌细胞上的KCa通道,导致细胞膜超极化从而抑制平滑肌细胞中游离Ca2+浓度的升高。
Objective To observe the vasodilatory effect of all-trans retinoic acid (ATRA) on vascular resistance and to explore its related mechanism. Methods Mesenteric arteries of healthy male Sprague Dawley (SD) rats were randomly divided into three groups: the intact endothelium ATRA group (n = 8), the ATRA group (n = 5) after endothelium removal and the solvent control group (n = 8). The effects of ATRA (1 × 10-8 to 3 × 10-6mol / L) on pre-contracted blood vessels of phenylephrine (PE, 1 × 10-5mol / L) were observed. L-monomethyl-arginine (l-NMMA, 1 × 10-5mol / L, n = 4), soluble guanylate cyclase (sGC) specific antagonist L, n = 5) and potassium channel antagonists [4 aminopyridine (1 × 10-4mol / L), glibenclamide (1 × 10-5mol / L) 10-5mol / L), n = 6] for 30min. The response of ATRA to blood vessels was observed to further explore its mechanism. Results ATRA reduced the tension of precontracted mesenteric artery rings of PE (1 × 10-5mol / L) in a concentration-dependent manner on the intact mesenteric artery of the endothelium. Compared with the intact endothelial ATRA-treated group, the maximal relaxation effect of ATRA was significantly (17.1 ± 6.7)% (65.5 ± 10.9)%, P <0.05]. L-NMMA, ODQ or beeintomycin + scorpion toxin significantly reduced the vasodilatation of ATRA, while 4-aminopyridine and glibenclamide had little effect on the vasodilatation of ATRA. Conclusion ATRA can relax vasoconstriction induced by PE. Its diastolic mechanism may be nitric oxide production by vascular endothelial cells, which in turn activate the downstream sGC, promote the synthesis of cyclic guanosine monophosphate and activate KCa channels on smooth muscle cells, resulting in hyperpolarization of the cell membrane and thus inhibit the concentration of free Ca2 + in smooth muscle cells Rise.