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目的研究金丝桃苷(hyperoside,Hyp)对全脑缺血再灌注(cerebral ischemia-reperfusion,CIR)大鼠离体大脑中动脉(middle cerebral artery,MCA)的舒张作用及其机制。方法采用动脉加压灌注法、细胞膜电位记录法分别观察(1×10-6~1×10-4)mol·L-1金丝桃苷对1×10-7mol·L-1U46619预收缩全脑缺血再灌注大鼠大脑中动脉的舒张作用和平滑肌细胞膜静息电位超极化反应;采用全自动酶标仪、硝酸还原酶法分别测定全脑缺血再灌注大鼠大脑组织硫化氢(H2S)和一氧化氮(NO)含量及金丝桃苷对其的影响。结果金丝桃苷能诱导U46619预收缩全脑缺血再灌注大鼠大脑中动脉产生明显的血管舒张反应和超极化现象(P<0.01),去除内皮细胞后,其效应显著减弱(P<0.01);单用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(3×10-5mol·L-1)或合用左旋硝基精氨酸甲酯(3×10-5mol·L-1)和前列环素合成酶抑制剂吲哚美辛(1×10-5mol·L-1)后,金丝桃苷介导大脑中动脉产生的舒张效应和超极化反应明显减弱,且全脑缺血再灌注组剩留的作用显著强于假手术(sham)组(P<0.05,P<0.01);1×10-3mol·L-1KCa通道阻断剂四乙胺或1×10-4mol·L-1胱硫醚-γ-裂解酶抑制剂炔丙基甘氨酸(PPG)能明显减弱金丝桃苷诱导全脑缺血再灌注组大脑中动脉产生的非一氧化氮非前列环素样效应;与全脑缺血再灌注组比较,金丝桃苷组能显著降低一氧化氮含量,提高硫化氢含量。结论金丝桃苷能介导全脑缺血再灌注大鼠大脑中动脉产生内皮依赖性与内皮非依赖性血管舒张效应和超极化反应;在内皮依赖性舒张效应中,一氧化氮功能是下调的,而血管内皮依赖性超极化因子(endothelium-derived hyperpolarizing factor,EDHF)是上调的,即内源性硫化氢是上调的;金丝桃苷能升高全脑缺血再灌注大鼠脑组织中硫化氢含量,降低一氧化氮含量,产生对抗脑缺血损伤的保护作用。
Objective To investigate the diastolic function and mechanism of hyperoside (Hyp) on isolated rat middle cerebral artery (MCA) after global cerebral ischemia-reperfusion (CIR). Methods Hyperbaric perfusion and arterial pressure perfusion were used to observe the effect of hyperoside (1 × 10-6 ~ 1 × 10-4) mol·L-1 hyperoside on 1 × 10-7mol·L-1U46619 precontracted whole brain The diastolic function of middle cerebral artery and the resting potential hyperpolarization of smooth muscle cell membrane were observed in ischemia-reperfusion rats. Hydrogen sulfide (H2S ) And nitric oxide (NO) content and hyperoside on its impact. Results Hyperin could induce vasorelaxation and hyperpolarization in the middle cerebral artery of pretreated rats with U46619 precontracted global cerebral ischemia and reperfusion (P <0.01). After removing endothelial cells, the effect of hyperoside was significantly weakened (P < 0.01). Nitric oxide synthase inhibitor L-NAME (3 × 10-5mol·L-1) or L-NAME (3 × 10-5mol·L- 1) and prostacyclin synthase inhibitor indomethacin (1 × 10-5mol·L-1), hyperin induced diastolic and hyperpolarization reactions of middle cerebral artery were significantly weakened, and all The residual effect of cerebral ischemia-reperfusion group was significantly stronger than that of sham group (P <0.05, P <0.01). The protective effect of 1 × 10-3 mol·L-1 KCa channel blocker tetraethylamine or 1 × 10- 4mol·L-1 cystathionine-γ-lyase inhibitor propargylglycine (PPG) can significantly reduce the non-nitric oxide non-nitric oxide non-prostacyclin Like effect; Compared with the global ischemia reperfusion group, hyperoside group can significantly reduce the content of nitric oxide and increase the content of hydrogen sulfide. Conclusion Hyperin can mediate endothelium-dependent and endothelium-independent vasodilatation and hyperpolarization in the middle cerebral artery during global cerebral ischemia-reperfusion in rats. In endothelium-dependent relaxation, nitric oxide function is Regulated while endothelium-derived hyperpolarizing factor (EDHF) is up-regulated, that is, endogenous hydrogen sulfide is up-regulated; hyperin can increase global cerebral ischemia-reperfusion injury in rats Hydrogen sulfide in brain tissue, reduce the content of nitric oxide, have a protective effect against cerebral ischemia injury.