肝功能衰竭肝性脑病大鼠5-羟色胺和去甲肾上腺素的变化

目的研究5-羟色胺(5-HT)及去甲肾上腺素(NA)在大鼠急性肝功能衰竭(ALF)和慢性肝功能衰竭(CLF)肝性脑病时的变化。方法将110只SD大鼠随机分为正常对照组(20只)、ALF组(45只)及CLF组(45只)。ALF模型按500mg/kg硫代乙酰胺(TAA)间隔24h两次灌胃;CLF模型按质量分数为0.03%的TAA作为饮用水灌饲10周,并根据每周体重的变化增减50%的TAA含量。造模成功后从眼底静脉丛取血,检测5-HT、NA、血氨和肝功能指标;处死动物,取肝、脑组织,光镜下观察组织病理学变化。结果ALF组和CLF组均出现不同程度的肝功能损害表现,血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)、白蛋白(ALB)、白蛋白/球蛋白(A/G)、血氨均有明显变化(P<0.05或P<0.01);肝脏及脑组织病理学符合ALF和CLF肝性脑病表现。ALF组和CLF组5-HT(16.06±1.08)μmol/L和(15.32±1.48)μmol/L均较正常对照组(2.75±0.26)μmol/L显著升高(P均<0.01),CLF组NA值下降(94.0±2.13)pmol/L比(121.2±14.8)pmol/L,P<0.05。结论5-HT在大鼠ALF和CLF所致肝性脑病时明显升高;NA在大鼠CLF所致肝性脑病时明显下降。

Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of liver failure in rat

OBJECTIVE: To investigate the changes in serotonin (5-HT) and noradrenaline (NA) in hepatic encephalopathy as a result of acute and chronic liver failure in rat. METHODS: One hundred and ten Sprague-Dawley (SD) rats were randomly divided into groups of normal control (n=20), experimental group of acute liver failure (ALF) encephalopathy (n=45), and experimental group of chronic liver failure (CLF) encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA dosage was added or withheld according to the change in weekly body weight measurement. Animals were sacrificed and venous blood specimens were obtained after successful replication of model, and 5-HT, NA, ammonia, parameters of liver function were determined, and liver and brain were studied pathologically. RESULTS: The experiment showed that the liver functions of rats in groups ALF encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(P<0.05 or P<0.01). The clinical manifestations, liver and brain pathologies were identical to those of ALF and CLF encephalopathy. The values of 5-HT were increased in groups ALF encephalopathy and CLF encephalopathy (16.06+/-1.08) micromol/L and (15.32+/-1.48) micromol/L] compared with the normal group (2.75+/-0.26) micromol/L, both P<0.01], while the value of NA decreased in the group of CLF encephalopathy (94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,P<0.05]. CONCLUSION: The levels of 5-HT are elevated in the groups of ALF encephalopathy and CLF encephalopathy. The content of NA decreases remarkably in CLF encephalopathy.