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孟爱宏, 凌亦凌,
王殿华, 谷振勇, 李淑瑾, 朱铁年
(河北医科大学病理生理教研室, 石家庄 050017)
摘 要:
为探讨八肽胆囊收缩素(CCK-8)缓解内毒素休克时肺动脉高压的作用机制, 应用离体血管环张力测定技术及一氧化氮合酶(NOS)检测方法,
观察了一氧化氮(NO)在CCK-8减轻肿瘤坏死因子-α (tumor necrosis factor-alpha, TNF-α)的抑制肺动脉内皮依赖性舒张反应中的作用。结果显示:
TNF-α (4,000 U/ml)孵育2 h时, 肺动脉对10-6 mol/L 苯肾上腺素(phenylephrine, PE)和10-6
mol/L 乙酰胆碱(ACh)的收缩反应及内皮依赖性舒张反应均无明显变化。TNF-α 孵育7 或14 h时, 肺动脉对10-6 mol/L ACh介导的内皮依赖性舒张反应降低,
CCK-8 (0.5 μg/ml)可逆转TNF-α 的上述作用。CCK-8本身对正常肺动脉反应性无明显影响。 TNF-α, CCK-8对PE引起的收缩反应无显著影响。L-精氨酸(L-Arg)可使TNF-α
7 h组内皮依赖性舒张作用恢复。氨基胍(AG)不影响各组肺动脉对10-6 mol/L ACh的内皮依赖性舒张反应, 而使TNF-α
组肺动脉环对10-6 mol/L PE的收缩反应显著增加。L-硝基精氨酸(L-NNA)使各组肺动脉环对10-6 mol/L ACh反应由舒张变为收缩, 对10-6 mol/L PE的收缩反应显著增强。检测7 h各组NOS活性,
TNF-α 组, TNF-α+CCK-8组均较对照组显著增加, CCK-8组与对照组比较无显著差异。上述结果提示, CCK-8可逆转TNF-α
对内皮依赖性舒张反应的抑制作用, 此作用可能与NO有关。
关键词:
缩胆囊素; 肿瘤坏死因子; 一氧化氮; 肺动脉; 血管反应性
学科分类号: Q954.6; R363
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MENG Ai-Hong, LING Yi-Ling, WANG Dian-Hua, GU Zhen-Yong, LI Shu-Jin, ZHU
Tie-Nian
(Department of Pathophysiology, Hebei Medical University, Shijiazhuang
050017)
Abstract:
To explore the mechanism underlying cholecystokinin-octapeptide (CCK-8)
induced attenuation in pulmonary arterial hypertension (PAH) in endotoxic
shock (ES), the effect of CCK-8 on the changes in rabbit pulmonary
arterial reactivity induced by tumor necrosis factor-alpha (TNF-α) was
observed with isolated arterial ring technique and by examination of
nitric oxide synthase (NOS). The contractile response to 10-6 mol/L
phenylephrine (PE) and the endothelium-dependent relaxation response to
10-6 mol/L acetylcholine (ACh) were not affected by TNF-α (4,000 U/ml)
after incubation for 2 h; the relaxation response was decreased
significantly when the incubation was prolonged to 7 or 14 h, which,
however, could be reversed by a concomitant exposure to CCK-8 (0.5 μg/ml),
but the incubation of pulmonary arterial rings with CCK-8 (0.5 μg/ml)
alone did not bring out any contractile responses. The
endothelium-dependent relaxation response to 10-6 mol/L ACh was restored
by L-arginine in the TNF-α group which had been incubated for 7 h, but was
not affected by AG in each group, while the contractile response to 10-6
mol/L PE increased significantly in the TNF-α group. The relaxant response
to 10-6 mol/L ACh changed into a contractile response after preincubation
with L-NNA in each group, while the contraction response to 10-6 mol/L PE
increased significantly. The NOS activity increased in the TNF-α and the
TNF-α+CCK-8 groups, while no significant difference was observed between
the vehicle and the CCK-8 groups. These results suggest that CCK-8
prevents TNF-α induced impairment in endothelium-dependent relaxation
response, and the effects of both CCK-8 and TNF-α are related to NO.
Key words:
cholecystokinin-octapeptide; tumor necrosis factor-alpha; nitric oxide;
pulmonary; vascular reactivity
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