Research On Function Of ACE2-Ang(1-7)-MasR Axis In Early Brain Injury After Cardiopulmonary Resuscitation In Rats

Objective: To discuss the function of ACE2-Ang(1-7)-Mas R axis in early brain injury after cardiac arrest-cardiopulmonary resuscitation in rats,and to provide new ideas for clinical treatment of brain injury after cardiopulmonary resuscitation.Methods: CA-CPR model was established by ventricular fibrillation(VF).54 l abratory rats were randomly divided into sham group(n=18),conventional resus citation group(n=18)and Mas R agonist Ang(1-7)group(n=18).Brain tissue and serum samples were collected after resuscitation for 2,4 and 6 hours,respectiv ely.NO and O2-expression in brain tissues were detected by colorimetry,AT1 R,AT2R,Mas R,e NOS and i NOS expression in brain tissues by q RT-PCR,A ng II,ACE,ACE2,Ang(1-7),S100 B and 3-NT expression in serum by ELISA,and AT1 R,AT2R,i NOS,e NOS and Mas R protein expression in brain tissues by Western Blot.Histopathological changes of hippocampal gyrus were detecte d by HE staining.Results: 1.Changes of RAS system,oxidative stress,nitrative stress response and brain injury after CA-CPR: Compared with sham group,Ang II,Ang(1-7),ACE,ACE2,AT1 R and AT2 R,3-NT、NO,O2-,i NOS and e NOSm RNA,e NO S and i NOS protein expression,S100 B expression were significantly increased in control group at 2h,4h,6h after CPR.Mas Rm RNA was increased in contro l group at 4h,6h after CPR.The difference was statistically significant(P<0.05).ACE,ACE2,AT1 R and AT2 R protein expression,Mas Rm RNA and Mas R protein expression,O2-,NO,e NOSm RNA and e NOS protein expression,and S100 B expression were all increased at 2,4 and 6 hours after CPR in Ang(1-7)group.AT1 R and AT2 R m RNA were increased at 4 and 6 hours after CPR in Ang(1-7)group.The expression of 3-NT and i NOS protein was increased slightly at 6 hours after CPR(P<0.05).2.The effects of Mas R agonist Ang(1-7)on RAS system,oxidative stress,nitrative stress response and brain injury a fter CA-CPR: Compared with control group,ACE,ACE2,AT1 R and AT2 Rm R NA,AT1 R and AT2 R protein expression,3-NT,O2-,i NOSm RNA and i NOS p rotein expression,S100 B concentration were all decreased at 2h,4h,6h after CPR,and the expression of e NOS protein decreased slightly 2 hours after CPR in Ang(1-7)group.Mas Rm RNA and Mas R protein expression,NO,e NOSm R NA were slightly decreased at 2h,4h,6h,respectively,after CPR.The express ion of e NOS protein expression was increased 4 and 6 hours after CPR in An g(1-7)group.The difference was statistically significant(P<0.05).3.The effects of CA-CPR and Mas R agonist Ang(1-7)on pathological changes of hippocamp al gyrus: Compared with Sham group,the pathological changes of hippocampal gyrus in control group and Ang(1-7)group at 6 hours after CPR showed spars e neurons pyknosis,irregular,deep-stained nuclei,irregular arrangement of cell s,interstitial edema,etc.Compared with control group,pathological interstitial edema of brain tissue,the number of pyknosis and deep staining decreased in Ang(1-7)group decreased slightly at 6 hours after CPR.Conclusion: 1.The oxidative stress and nitrative stress response in early brain tissue were over-activated after CA-CPR.2.Early ACE2-Ang(1-7)-Mas R axis activation after CA-CPR can reduce oxidative stress and nitrification stress by up-regulating the expression of e NOS and down-regulating the expression of O2-,i NOS,and slightly alleviating the pathological damage of brain tissue.