Objective To explore the role of renin-angiotensin system( RAS) in acute lung injury( ALI) /acute respiratory dysfunction syndrome( ARDS) by using amouse cecal ligation and puncture ( CLP)model.Methods The ALI/ARDS animal models were assessed bymeasuring blood gas, wet/dry lung weight ratio( W/D) , and lung tissue histology 18 hours after CLP operation. After the ALI/ARDS models was successfully established, immunohistochemistry, western blotting and radioimmunity were used to investigate the changes of several key enzymes of RAS, such as ACE, ACE2 and Ang Ⅱ. In addition, two groups of animals received a separate intraperitoneal injection of angiotensin-converting enzyme ( ACE) inhibitor captopril or recombinant mouse ACE2 ( rmACE2) after CLP, then the changes of RAS in ALI/ARDS modelswere observed. Results The extensive lung injuries can be observed in the lung tissues from CLP-treated animals 18 hours after operation. The CLP-induced ALI/ARDS led to an increase in the wet/dry weight ratio of the lung tissues, and a decrease in the PaO2 /FiO2 [ ( 194. 3 ±23. 9) mm Hg vs ( 346. 7 ±20. 5) mm Hg,P lt;0. 01] . Immunohistochemistry and western blotting tests of the lung tissues from CLP-treated animals showed a decrease in the ACE2 protein level. However, in both the CLP and sham mice there were no significant differences between the two groups. CLP markedly increased Ang Ⅱ level in lungs and plasma of mice, and RAS drugs significantly impacted the Ang Ⅱ levels of mice. Compared with the CLP group,captopril or rmACE2 led to a decrease of the Ang Ⅱ level in mice [ Lung: ( 1. 58 ±0. 16) fmol /mg,( 1. 65 ±0. 21) fmol /mg vs ( 2. 38 ±0. 41) fmol /mg; Plasma: ( 178. 04 ±17. 87) fmol /mL, ( 153. 74 ±10. 24) fmol /mL vs ( 213. 38 ± 25. 44) fmol /mL] . Conclusions RAS activation is one of the characteristics of CLP-induced ALI/ARDS in mice models. ACE and ACE2 in RAS have a different role in the regulation of AngⅡ synthesis, while ACE has a positive effect in generating AngⅡ, and ACE2 shows a negative effect.
Objective To investigate the role of angiotensin-II type 1 receptor ( AT1) antagonist in treatment of acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods Animal model of ALI/ARDS was induced by cecal ligation and perforation ( CLP) . ALI/ARDS animals received a separate intraperitoneal injection of several concentrations( 5, 10, 15, 20, 25 mg/kg) of AT1 inhibitor losartan after CLP, then the changes of lung injury and 7-day survival were measured. Results Oxygenation index and lung wet to dry weight ratio ( W/D) showed an improving trend when losartan was administered at doses of 5 to 15 mg/kg in ALI/ARDS rats, but aggravated above the dose of 15 mg/kg. Losartan ( 15 mg/kg) treatment significantly alleviated pulmonary edema after CLP operation, and decreased serumlevels of TNF-α, IL-6, andIL-1β [ TNF-α: ( 554. 1 ±62. 7 ) pg/mL vs. ( 759. 2 ±21. 5 ) pg/mL, P lt; 0. 01; IL-6: ( 1227. 3 ±130. 0) pg/mL vs. ( 2670. 4 ±174. 1) pg/mL, P lt; 0. 01; IL-1β: ( 444. 0 ±38. 6) pg/mL vs. ( 486. 6 ±61. 7)pg/mL, P lt; 0. 05] . 7-day survival rate also increased in losartan treatment group at a dose of 15 mg/kg( 6. 7% vs. 0 ) . Conclusions The AT1 inhibitor, losartan, can significantly prevent lung injury in ALI/ARDS after CLP, and improve the 7-day survival rate.
Objective To explore the changes and effect of plasma renin-angiotensin system (RAS) and nitric oxide (NO) in rabbits pericarditis. Methods Twenty-one male rabbits were divided into two groups randomly. Experimental group: 11 rabbits were injected 40% urea (2ml/kg) into pericardial cavity, control group: 10 rabbits were injected 0.9% natrium chloride into the pericardial cavity . The concentration of plasma renin active (RA), angiotensin Ⅱ(ANGⅡ) and NO were measured before operation and after operation 1,4,7,10,15,21 days. The histopathological changes of pericardium, myocardium, lung and liver were observed in the adopted specimens. Results The concentration of plasma RA, ANGⅡ and NO in experimental group increased after operation and significantly increased at 7 to 21 day compared with those in control group (Plt;0.01). In the experimental group, there were proliferation and thickening of pericardium, myocardial degeration, pulmonary ecchymosis and hepatic ecchymosis. Conclusion The concentration of plasma RAS and NO is increased in rabbits with pericarditis, plasma NO rejects the roles of RAS, NO and RAS lead to organs injury of pericardium, myocardium, lung, liver and so on.
ObjectivesTo systematically review the efficacy of different rennin-angiotensin system blockers in prevention of stroke recurrence and reduction of major vascular events in patients with prior stroke.MethodsPubMed, The Cochrane Library, EMbase, CNKI, CBM and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of ACEIs and ARBs for stroke secondary prevention from inception to November 1st, 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies. Network meta-analysis was then performed by using Stata 15.1 software.ResultsA total of 6 RCTs involving 25 620 patients were included. The results of network meta-analysis showed that: in prevention of stroke recurrence, candesartan (RR=0.40, 95%CI 0.16 to 0.99) and valsartan (RR=0.22, 95%CI 0.07 to 0.76) were significantly lower than placebo; valsartan was lower than telmisartan (RR=0.24, 95%CI 0.07 to 0.81), ramipril (RR=0.26, 95%CI 0.07 to 0.93) and perindopril (RR=0.23, 95%CI 0.07 to 0.81). For reducing the major vascular events after stroke, candesartan (RR=0.39, 95%CI 0.21 to 0.74), valsartan (RR=0.27, 95%CI 0.11 to 0.64) and ramipril (RR=0.76, 95%CI 0.60 to 0.95) were significantly lower than placebo; valsartan was lower than telmisartan (RR=0.29, 95%CI 0.12 to 0.69), ramipril (RR=0.36, 95%CI 0.15 to 0.88) and perindopril (RR=0.28, 95%CI 0.12 to 0.68); candesartan was lower than telmisartan (RR=0.42, 95%CI 0.22 to 0.79) and perindopril (RR=0.41, 95%CI 0.21 to 0.79).ConclusionsCurrent evidence shows that valsartan and candesartan can reduce the stroke recurrence and major vascular events after stroke. Ramipril can reduce the major vascular event in patients with prior stroke. Valsartan might be the best option in both outcomes. Due to limited quantity of the included studies, more high quality studies are required to verify above conclusions.