一氧化氮合酶抑制剂口服两周治疗对肝硬化大鼠高动力循环状态的影响(英文)

Effects of nitric oxide synthase inhibitor in two-week oral treatment on hyperdynamic circulatory state in cirrhotic rats

目的 :观察小剂量一氧化氮合酶 (NOS)抑制剂N -硝基 -L -精氨酸甲酯 (L -NAME)连续 2周治疗对肝硬化大鼠高动力循环状态的影响。方法 :用 6 0 %四氯化碳油性溶液皮下注射SD大鼠制造肝硬化大鼠模型。对肝硬化大鼠 ,用L -NAME (0 5mg·kg-1·d-1)胃管内注入连续治疗 2周。用 57Co同位素微球技术分别测定L -NAME治疗组、未治疗组及正常对照组的平均动脉压 (MAP)、门静脉压 (PP)、心输出量 (CO) 、心脏指数 (CI)、内脏血管阻力 (SVR)及内脏器官血流量 (SBF)。用荧光法测定各组大鼠血清亚硝酸盐含量。结果 :未治疗组MAP、SVR显著低于正常对照组 ,而PP、CO、CI、SBF及亚硝酸盐含量则显著高于正常对照组 (P值均小于0 0 1)。在治疗组 ,L -NAME显著缓解了CO、CI、SBF及亚硝酸盐浓度的增加和MAP、SVR的下降。与未治疗组比较 ,治疗组血清亚硝酸盐浓度明显减少 [(1 471± 0 90 7) μmol/Lvs (4 2 0 4± 1 2 5 3) μmol/L ,P <0 .0 1]。 结论 :内源性NO在肝硬化血流动力学改变中可能起重要作用。小剂量L -NAME连续

AIM: To investigate the effects of low dosage of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester(L-NAME)in two-week treatment on the hyperdynamic circulatory state in rats with cirrhosis. METHODS: Cirrhosis model was induced in male SD rats by injection of 60% CCl 4 oily solution subcutaneously.Cirrhotic rats were treated with L-NAME(0.5 mg·kg -1·d -1) by gavage for two weeks. Mean arterial pressure(MAP), portal pressure(PP), cardiac output(CO),cardiac index(CI), splanchnic vascular resistance(SVR), splanchnic blood flow(SBF) and serum nitrite levels were determined in L-NAME-treated,L-NAME-untreated cirrhotic rats and controls by using 57Co-labled microsphere technique and a fluorometric assay, respectively. RESULTS:Untreated cirrhotic rats had significantly lower MAP, SVR and higher PP,CO,CI,SBF and nitrite concentration than those of the controls (all, P<0.01). In treated cirrhotic rats, L-NAME significantly attenuated the increase of CO, CI, SBF, nitrite concentration and the decrease of MAP and SVR.In treated cirrhotic rats, L-NAME induced a marked decrease of nitrite concentration than untreated cirrhotic rats[(1.471±0.907) μmol/L vs (4.204±1.253) μmol/L, P<0.01]. CONCLUSION: The endogenous NO may play an important role in the changes of hemodynamics pattern in cirrhosis, and hyperdynamic circulatory state in rats with cirrhosis can be ameliorated by oral two-week administration of lower dose of L-NAME.