肠淋巴液引流对失血性休克小鼠心肌组织ACE/ACE2的作用

Role of mesenteric lymph drainage in the balance of ACE / ACE2 in murine myocardium following hemorrhagic shock

目的:观察失血性休克后小鼠心肌组织血管紧张素转换酶(ACE)/ACE2平衡的变化及肠淋巴液引流(PHSML)的作用。方法:BALB/c雄性小鼠24只,随机分为对照组、假手术组、休克组、休克+引流组(n=6)。建立失血性休克模型,行液体复苏;休克+引流组液体复苏后,引流肠淋巴液。在液体复苏后6 h或假手术组相应时间点、对照组于麻醉后,留取心肌组织,q RT-PCR法检测ACE、ACE2、血管紧张素II(Ang II)1型受体(AT1R)、Mas相关G蛋白偶联受体(Mas1R)的mRNA表达,ELISA方法检测Ang II和Ang(1-7)含量。结果:休克组小鼠心肌组织ACE与AT1R mRNA表达、Ang II水平均显著高于对照组与假手术组,ACE2与Mas1R mRNA表达显著低于对照组与假手术组、Ang(1-7)含量显著低于对照组,ACE/ACE2、Ang II/Ang(1-7)、AT1R/Mas1R显著高于对照组与假手术组;PHSML引流显著抑制了失血性休克对这些指标的作用。结论:失血性休克上调心肌ACE-Ang II-AT1R轴、下调ACE2-Ang(1-7)-Mas1R轴表达,引起ACE/ACE2失衡;PHSML引流下调ACE-Ang II-AT1R轴、上调ACE2-Ang(1-7)-Mas1R轴表达,在一定程度上维持了ACE/ACE2平衡。

Objective： To observe the change of angiotensin converting enzyme（ ACE） and ACE2 in the murine myocardium followed hemorrhagic shock and the role of post-hemorrhagic shock mesenteric lymph（ PHSML） drainage. Methods： Twenty-four male mice were randomly divided into control,sham,shock,and shock ＋ drainage groups. A hemorrhagic shock model was established and then fluid resuscitation was performed to the mice in the shock and shock ＋ drainage groups,and the PHMSL was drained in the shock＋ drainage group after fluid resuscitation. After 6 h of resuscitation in the shock and shock ＋ drainage groups or corresponding time in the sham group,or after anesthesia in the control group,the myocardial tissues were harvested for the determination of the m RNA expressions of ACE,ACE2,angiotensin II（ Ang II） type 1 receptor（ AT1R）,and Mas related G protein coupled receptor（ Mas1R） using the method of q RT-PCR,and the levels of Ang II and Ang（ 1-7） using the method of ELISA. Results： In the myocardial tissue of shock group,the ACE and AT1 R m RNA expressions and Ang II level were significantly increased than those of the control and sham groups,the ACE2 and Mas1 R m RNA expressions were significantly decreased than that of the control and sham groups,the Ang（ 1-7）level was decreased compared with the control group,the ratios of ACE / ACE2,Ang II / Ang（ 1-7）,and AT1 R / Mas1 R in the shock group were significantly increased than the control and sham groups. Meanwhile,PHSML drainage obviously suppressed the effects of hemorrhagic shock on these indices. Conclusion： Hemorrhagic shock up-regulated the ACE-Ang II-AT1 R axis,down-regulated the ACE2-Ang（ 1-7）-Mas1 R axis,and induced the unbalance of ACE and ACE2 in myocardial tissue. PHSML drainage decreased the ACE-Ang II-AT1 R axis and increased the ACE2-Ang（ 1-7）-Mas1 R axis,resulted in the balance of ACE and ACE2.