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Role of PGI2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats.

机译:PGI2在门脉高压大鼠高动力循环状态形成和维持中的作用。

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AIM: To investigate the role of prostacyclin (PGI(2)) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCl(4), prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nomega-nitro-L-arginine (L-NNA) group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1 mL of saline, L-NNA (3.3 mg/kg.d) and INDO (5 mg/kg.d) respectively through gastric tubes for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrateitrite (NO(2)(-)/NO(3)(-)) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1alpha, a stable hydrolytic product of PGI(2), was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGF1alpha (pg/mL) and serum NO(2)(-)/NO(3)(-) (micromol/L) in IHPH rats (1123.85+/-153.64, 73.34+/-4.31) and PHPH rats (891.88+/-83.11, 75.21+/-6.89) were significantly higher than those in SO rats (725.53+/-105.54, 58.79+/-8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1alpha and serum NO(2)(-)/NO(3)(-) in IHPH and PHPH rats (P<0.05). Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased (P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI(2), NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto-PGF(1alpha) concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO(2)(-)/NO(3)(-) in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI(2) that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.
机译:目的:探讨前列环素(PGI(2))和一氧化氮(NO)在慢性门脉高压大鼠高动力循环状态的发展和维持中的作用。方法:将90只雄性Sprague-Dawley雄性大鼠分为三组:通过注射CCl(4)肝内门脉高压(IHPH)组,通过门静脉部分狭窄和假手术控制(SO)的肝前门脉高压(PHPH)组。 )组。制作模型一周后,将每组动物分为4组:盐水对照组(n = 23),Nomega-硝基-L-精氨酸(L-NNA)组(n = 21)组,消炎痛(INDO) )组(n = 22)和大剂量肝素组(n = 24)。分别通过胃管给大鼠1 mL生理盐水,L-NNA(3.3 mg / kg.d)和INDO(5 mg / kg.d),持续一周,然后给予肝素(200 IU / Kg / min)。给大鼠静脉注射一个小时。使用放射性微球技术测量内脏和全身的血流动力学。通过比色法评估血清硝酸盐/亚硝酸盐(NO(2)(-)/ NO(3)(-))水平作为NO生成的标志物,并测定6-酮-PGF1alpha(一种稳定的水解产物)的浓度通过放射免疫测定法测定PGI(2)的值。结果:IHPH大鼠血浆6-酮-PGF1alpha(pg / mL)和血清NO(2)(-)/ NO(3)(-)(micromol / L)的浓度(1123.85 +/- 153.64,73.34+ (--4.31)和PHPH大鼠(891.88 +/- 83.11,75.21 +/- 6.89)显着高于SO大鼠(725.53 +/- 105.54,58.79 +/- 8.47)(P <0.05)。与SO大鼠相比,IHPH和PHPH大鼠的总外周血管阻力(TPR)和司盘血管阻力(SVR)降低,但心脏指数(CI)和门静脉流入(PVI)明显增加(P <0.05)。 L-NNA和消炎痛可降低IHPH和PHPH大鼠血浆6-酮-PGF1α的浓度和血清NO(2)(-)/ NO(3)(-)(P <0.05)。同时,CI,FPP和PVI降低,而MAP,TPR和SVR增加(P <0.05)。扣除NO的作用后,血浆PGI(2)水平与血流动力学参数(如CI,TPR,PVI和SVR)之间没有显着相关性。但是,扣除PGI(2)的作用后,NO仍与血液动力学参数高度相关,这表明NO与血液动力学参数之间存在密切相关性。大剂量肝素给药后,IHPH,PHPH和SO大鼠血浆6-酮-PGF(1α)浓度显着高于给药载体的大鼠(P <0.05)。相反,IHPH,PHPH和SO大鼠的血清NO(2)(-)/ NO(3)(-)水平显着低于施用媒介物的大鼠(P <0.05)。与给药载体相比,大剂量肝素给药后门静脉高压大鼠的血流动力学参数如CI和PVI显着下降(P <0.05),而TPR和SVR显着升高(P <0.05)。结论:在慢性门脉高压大鼠高动态循环状态的形成和维持中,不是PGI(2),而是NO。

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