内毒素血症大鼠肝脏RAS表达与肝功能损伤的关系

Relationship between RAS expression and liver function injury in endotoxemia model rats

目的探讨内毒素血症大鼠肝脏肾素-血管紧张素系统(RAS)的表达特点及其与肝功能损伤的关系。方法将90只大鼠随机分为对照组和注射后2、4、8、12、24、48、72 h及7 d组。除对照组以外,均腹腔注射脂多糖(LPS)制备脓毒症模型。分别于注射2、4、8、12、24、48、72 h及7 d取10只,取心脏血,测肝功能标志物丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH),循环RAS标志物肾素(PRA)、血管紧张素转换酶(ACE)、血管紧张素Ⅱ(AngⅡ);取肝脏组织,观察肝组织病理,测组织RAS标志物PRA、ACE、AngⅡ及血管紧张素1型受体(AT1R)mRNA表达。结果模型组大鼠的循环AST、ALT及LDH水平在LPS注射后逐渐升高,8 h达峰,AST与LDH在4~48 h均高于对照组,ALT在2~48 h均高于对照组,差异有统计学意义(P<0.05)。模型组大鼠的循环和肝脏PRA在注射后迅速升高,2 h达峰,48 h降至正常水平,中间时间段均高于对照组(P<0.05);ACE和AngⅡ在注射后逐渐升高,8 h达峰,ACE在2~24 h高于对照组,AngⅡ在2~48 h高于对照组,差异有统计学意义(P<0.05)。模型组大鼠AT1RmRNA表达在注射后逐渐升高,4~48 h均高于对照组,差异有统计学意义(P<0.05)。结论内毒素血症所致肝功能损伤可能与肝脏局部RAS激活有关系。

Objective To investigate the changes of liver renin-angiotensin(RAS)system as well as its relationship with liver function in endotoxemia rats.Methods Totally 90 rats were randomly divided into control group and 2,4,8,12,24,48,72 h and 7 d after injection group,which were prepared for sepsis model by tail vein injection of LPS except for the control group.Animals in the control group were collected samples at 8 h after injection,while animals in the model group were collected samples at each time points(2,4,8,12,24,48,72 h and 7 d).Heart blood was collected to measure liver markers alanine amine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),RAS markers renin-angiotensin(PRA),angiotensin converting enzyme(ACE)and angiotensinⅡ(AngⅡ).Liver tissues were extracted to observe the pathology characteristics and detect PRA,ACE,AngⅡand angiotensin type 1 receptor(AT1R)mRNA.Results The levels of AST,ALT and LDH in the model group gradually increased after LPS injection,and AST and LDH in the model group were higher than those in the control group at 4~48 h,ALT in the model group was higher than that in the control group at 2 to 48 h,and the differences were statistically significant(P<0.05).The circle and liver PRA level in the model group increased rapidly after injection,which was higher than that in the control group at 2 to 48 h.The circle and liver levels of ACE and AngⅡincreased after injection too,which were both higher than those in the control group at 2 to 28 h,and the difference was statistically significant(P<0.05).The expression of AT1R mRNA in the model group gradually increased after injection,which was higher than that in the control group at 4 to 48 h,and the difference was statistically significant(P<0.05).Conclusion Liver function damage caused by endotoxemia may be related to the activation of local RAS in the liver.