血管紧张素转换酶Ⅱ在中毒大鼠肝脏中的作用与机制分析

本研究旨在观察血管紧张素转换酶Ⅱ(Angiotensin Converting EnzymeⅡ,ACE2)在CCl4中毒大鼠肝脏中的表达,并探讨其参与抗损伤的作用机制。16只120 g左右雄性SD大鼠随机分成对照组和试验组(n=8)。对照组大鼠腹腔注射生理盐水,试验组大鼠腹腔注射40%CCl4,首次剂量为5 mL.kg-1,以后每3 d 1次(剂量为3mL.kg-1),每周称重1次,4周后宰杀。测定平均日增体质量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、白蛋白(Alb)、总蛋白(TP)、总胆红素(TBIL)、血浆血管紧张素Ⅱ(AngⅡ)含量、肝组织中ACE2含量和Mas受体mR-NA的表达及ACE2 mRNA的分布。结果表明:与对照组相比,试验组大鼠平均日增体质量、血清Alb和TP含量均显著下降(P0.05),血清ALT和AST活性显著升高(P0.05),血清TBIL和血浆AngⅡ含量没有显著性变化,Real-time PCR结果提示肝脏中ACE2和Mas受体的mRNA表达均显著上升(3.21±0.52 vs 1.03±0.11,P0.01;1.64±0.22 vs 1.02±0.10,P0.05),原位杂交结果显示对照组大鼠ACE2 mRNA着色较少,主要集中在中央静脉周围细胞,试验组大鼠ACE2大量出现在病变区域、胆管周围细胞、血管及微管内皮细胞当中。本研究表明CCl4诱导的肝损伤大鼠肝脏中ACE2和Mas受体的mRNA表达均增加,提示ACE2参与了肝脏的抗损伤过程,其机制可能是通过激活ACE2-Ang 1-7-Mas轴,减少AngⅡ的产生,从而减轻肝损伤。

Effect and Mechanism of ACE2 on Injury Liver in Rats

The aim of this research was to observe the expression of ACE2 on injury liver which induced by CC1_4 , and its mechanism of anti-injury. 16 SD rats was randomly divided into two groups: control group and experiment group. The rats in control group were injected strokephysiological saline solution and the experiment group were injected 40% CC1_4 , respectively. The first dosage was 5 mL·kg~(-1), then 3 mL·kg~(-1) every three days. Four weeks later, the activities of ALT, AST and the concentrations of albumin, total protein , total bilirubin and Ang II were detected. We also analyzed the distribution and expression of ACE2 and Mas on liver by Realtime PCR and hybridization in situ. Compared with control group, the average daily weight gain,the concentration of albumin and total protein were markedly reduced (P<0. 05) , but the activities of ALT and AST were obviously increased (P<0. 05). The concentrations of TBIL and Ang II had no significantly different compared with control group. The mRNA expression levels of ACE2 and Mas receptor were increased(3. 21±0. 52 vs 1. 03 ± 0. 11, P<0. 01;1. 64±0. 22 vs 1. 02±0. 10, P<0. 05). The distribution of ACE2 was widespread throughout cirrhotic nodules,bile duct cells and endothelial cells lining small blood vessels. The expression of ACE2 and Mas receptor on injury induced by CC14 in rats were increased significantly, which suggested that ACE2 may play an important role on injury liver by activating the ACE2-Ang 1-7-Mas axis to rival the effect of Ang II which could evoke injury.