CAJ | 학술논문

目的观察血红素氧合酶-一氧化碳系统对肝硬化大鼠全身血流动力学的影响.方法将30只雄性SD大鼠分为对照组(14只)和肝硬化组(16只),肝硬化组大鼠皮下注射50%四氯化碳(以橄榄油稀释,0.003 ml/g),对照组给予相同剂量的橄榄油.12周后,将肝硬化组大鼠分为肝硬化给药组(8只)、肝硬化模型组(8只),对照组大鼠分为正常给药组(7只)、正常对照组(7只).肝硬化给药组和正常给药组大鼠经后颈部皮下注射锌原卟啉(20 μmol/kg),肝硬化模型组和正常对照组予以等渗盐水,用动脉插管生理多导仪记录心率、平均动脉压的变化,门静脉插管测定门静脉压,联二亚硫酸盐还原法测定血浆一氧化碳水平,用比色法测定胆红素生成量.数据间比较用t检验.结果正常对照组与肝硬化模型组大鼠平均动脉压分别为(18.9±0.9)kPa和(15.6±1.7)kPa,门静脉压分别为(8.8±0.3)cm H2O(1 cm H2O=0.098 kPa)和(16.7±0.8)cm H2O,血浆一氧化碳分别为(10.4±1.3)μmol/L和(18.0±1.9)μmol/L,脾脏血红素氧合酶(HO)活性分别为(6.5±0.9)nmol·mg1·h1和(11.1±0.9)nmol·mg 1·h-1,小肠HO活性分别为(1.3±0.2)nmol·mg1·h-1和(2.5±0.1)nmo1·mg-1·h-1,两组比较,t值分别为4.52、23.10、8.42、9.28、15.10,P值均＜0.01,差异有统计学意义.正常对照组与肝硬化模型组大鼠肝脏HO活性分别为(2.7±0.2)nmol·mg-1·h-1、(2.7±0.1)nmol·mg-1·h-1,差异无统计学意义.肝硬化模型组、肝硬化给药组平均动脉压分别为(15.6±1.7)kPa、(17.3±1.5)kPa,两组比较,t=2.18,P＜0.05,差异有统计学意义,门静脉压分别为(16.7±0.8)cmH2O、(13.2±0.7)cmH2O,两组比较,t=8.53,P＜0.01,差异有统计学意义.结论 HO-CO系统的激活可能是肝硬化血流动力紊乱的重要原因.
목적 관찰혈홍소양합매-일양화탄계통대간경화대서전신혈류동역학적영향.방법장30지웅성SD대서분위대조조(14지)화간경화조(16지),간경화조대서피하주사50%사록화탄(이감람유희석,0.003 ml/g),대조조급여상동제량적감람유.12주후,장간경화조대서분위간경화급약조(8지)、간경화모형조(8지),대조조대서분위정상급약조(7지)、정상대조조(7지).간경화급약조화정상급약조대서경후경부피하주사자원계람(20 μmol/kg),간경화모형조화정상대조조여이등삼염수,용동맥삽관생리다도의기록심솔、평균동맥압적변화,문정맥삽관측정문정맥압,련이아류산염환원법측정혈장일양화탄수평,용비색법측정담홍소생성량.수거간비교용t검험.결과 정상대조조여간경화모형조대서평균동맥압분별위(18.9±0.9)kPa화(15.6±1.7)kPa,문정맥압분별위(8.8±0.3)cm H2O(1 cm H2O=0.098 kPa)화(16.7±0.8)cm H2O,혈장일양화탄분별위(10.4±1.3)μmol/L화(18.0±1.9)μmol/L,비장혈홍소양합매(HO)활성분별위(6.5±0.9)nmol·mg1·h1화(11.1±0.9)nmol·mg 1·h-1,소장HO활성분별위(1.3±0.2)nmol·mg1·h-1화(2.5±0.1)nmo1·mg-1·h-1,량조비교,t치분별위4.52、23.10、8.42、9.28、15.10,P치균＜0.01,차이유통계학의의.정상대조조여간경화모형조대서간장HO활성분별위(2.7±0.2)nmol·mg-1·h-1、(2.7±0.1)nmol·mg-1·h-1,차이무통계학의의.간경화모형조、간경화급약조평균동맥압분별위(15.6±1.7)kPa、(17.3±1.5)kPa,량조비교,t=2.18,P＜0.05,차이유통계학의의,문정맥압분별위(16.7±0.8)cmH2O、(13.2±0.7)cmH2O,량조비교,t=8.53,P＜0.01,차이유통계학의의.결론 HO-CO계통적격활가능시간경화혈류동력문란적중요원인.
Objective To investigate the role of heme oxygenase(HO), a catalyzing enzyme of heme to produce CO, in modulation of systemic circulation in CCl4-induced cirrhotic rats. Methods Saline (vehicle) and ZnPP were s.c. injected into the posterior necks of rats respectively and the rats were then anesthetized by pentobarbital sodium in four hours. Mean arterial pressure (MAP, kPa), heart rate (HR, b/min) and portal pressure (PP, cm/H2O) were measured by indwelling catheter. Plasma CO was determined by Chalmers method. Heme oxygenase acivity was determined by the rate of bilirubin formation. Results The cirrhotic rats showed significant hyperdynamic circulation indicated by decreased mean arterial pressure [MAP,(15.6 ± 1.7) vs (18.9 ± 0.9) kPa, t = 4.52, P ＜ 0.01] and increased portal pressure [PP, (16.7 ± 0.8)vs (8.8 ± 0.3) cm H2O, t = 23.10, P ＜ 0.01] as compared to normal control rats(NS). ZnPP could cause a significant increase in MAP [(17.3 ± 1.5) vs (15.6 ± 1.7) kPa, t = 2.18, P ＜ 0.05] and significant decrease in PP [(13.2 ± 0.7) vs (16.7 ± 0.8) cm H2O, t = 8.53, P ＜ 0.01] in cirrhotic rats. The cirrhotic group presented a significant increase in plasma CO [(18.0 ± 1.9) vs (10.4 ± 1.3) μ mol/L, t = 8.42, P ＜ 0.01] and HO activity in the spleens [(11.1 ± 0.9) vs (6.5 ± 0.9) nmol bilirubin/mg protein/h, t = 9.28, P ＜ 0.01 ] and intestines [(2.5 ±0.1) vs. (1.3 ± 0.2) nmol bilirubin/mg protein/h, t = 15.1, P ＜ 0.01]. ZnPP could cause significant decreases in plasma CO and HO activity in liver, spleen and intestine of both control and cirrhotic rats. Conclusion HO-CO system activation may be an important reason for the hemodynamic disturbance of liver cirrhosis.