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OBJECTIVE To explore the mechanism of Tingli dazao xiefei decoction on ventricular remodeling in model rats with heart failure after myocardial infarction. METHODS The rat model of heart failure after myocardial infarction was established by ligation of anterior descending branch of left coronary artery， which was divided into 8 groups： sham operation group， model group， A779 group （1 mg/kg）， A779 （1 mg/kg）+Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， A779 （1 mg/kg） +Tingli dazao xiefei decoction high-dose group （1.6 g/kg）， Tingli dazao xiefei decoction equivalent-dose group （0.8 g/kg）， Tingli dazao xiefei decoction high-dose group （1.6 g/kg） and losartan potassium group （10 mg/kg）. Each group was given equal volume of distilled water or corresponding drugs intragastrically for 4 weeks. Masson staining was used to determine the distribution of collagen fibers in rat myocardium. The content of hydroxyproline （Hyp） in myocardium was determined by alkaline hydrolyzation. The expressions of type Ⅰ and Ⅲ collagen （COLⅠ， COLⅢ）in myocardium were detected by immunohisto-chemistry. Myocardial fibrosis-related indexes such as matrix metalloproteinase-2 （MMP-2）， MMP-9， tissue inhibitor of metalloproteinase-1 （TIMP-1） and soluble suppression of tumorigenicity-2 （sST-2） were detected by ELISA. The protein expressions of angiotensin converting enzyme 2-angiotensin-（1-7）-Mas [ACE2-Ang-（1-7）-Mas] axis were detected by Western blot. RESULTS Compared with sham operation group， myocardial cells in model group and A779 group were disordered， collagen fiber deposition was significantly increased and myocardial fibrosis was obvious； the Hyp content and MMP-2， MMP-9， sST-2 levels were increased， and COL Ⅰ and COL Ⅲ positive expressions were significantly enhanced； TIMP-1 level， protein expressions of ACE2， Ang-（1-7） and Mas were significantly decreased （P＜0.05）. Compared with model group， above indexes of Tingli dazao xiefei decoction equivalent-dose and high-dose groups were improved to different extents. Compared with A779 group， A779+Tingli dazao xiefei decoction equivalent-dose and A779+high-dose groups could improve myocardial arrangement and collagen distribution， reduce the Hyp content and MMP-2， MMP-9 levels， reduce positive expressions of COL Ⅰ and COL Ⅲ （P＜0.05）， but couldn’t improve Ang-（1-7） and Mas protein expression. CONCLUSIONS Tingli dazao xiefei decoction can improve ventricular remodeling in myocardial failure model rats after myocardial infarction by improving the expression of ACE2- Ang（- 1-7）-Mas axis proteins.
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ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg-1·d-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.
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ABSTRACT Objective: The incidence of diabetic nephropathy (DN) is gradually increasing worldwide. Podocyte injury, such as podocyte apoptosis and loss of the slit diaphragm (SD)-specific markers are early pathogenic features of DN. Materials and methods: The cultured mouse podocytes were separated into a high glucose-treated (HG, 30mM) group to mimic DN in vitro, a low glucose-treated (LG, 5mM) group as a control and HG+ angiotensin-(1-7)(Ang-(1-7)) and HG+Ang-(1-7) + D-Ala7-Ang-(1-7) (A779, Ang-(1-7)/Mas receptor antagonist) experimental groups. The Cell Counting Kit-8 (CCK-8) method and flow cytometry was used to detect podocyte activity and podocyte apoptosis respectively. The expression of angiotensin type 1 receptor (AT1R), Mas receptor (MasR) and podocyte-specific markers were examined by q-PCR and Western blot, respectively. Results: The results showed that the decrease in podocyte activity; the increase in podocyte apoptosis; the decreased mRNA and protein expression of nephrin, podocin, WT-1 and MasR; and the upregulated expression of AT1R induced by HG could be reversed by Ang-(1-7). However, these effects were blocked by A779. The possible mechanisms of the Ang-(1-7)-mediated effect depended on MasR. In addition, the protective effect of Ang-(1-7) on podocyte activity was dose-dependent and most obvious at 10 µM. A779 had the greatest antagonistic action against Ang-(1-7) at a concentration of 10 μM. Conclusion: This study reveals that binding of Ang-(1-7) to its specific receptor MasR may counteract the effects of Ang II mediated by AT1R to significantly attenuate podocyte injury induced by high glucose. Ang-(1-7)/MasR targeting in podocytes may be a therapeutic approach to attenuate renal injury in DN.
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Objective:To study the effect of Fushengong prescreption on the regulation-antagonism effect of angiotensin converting enzyme-angiotensin Ⅱ-angiotensin Ⅱ 1 receptor （ACE-AngⅡ-AT1R） axis and angiotensin converting enzyme 2-angiotensin （1-7）-Mas receptor［ACE2-Ang（1-7）-MASR］ axis of rats with chronic renal failure（CRF）， and to explore its mechanism of delaying the development of CRF. Method:The 65 male SD rats were randomly divided into normal group （<italic>n</italic>=10） and modeling group （<italic>n</italic>=55）. The normal group was routinely reared， while the modeling group were administered by gavage with 0.25 g·kg<sup>-1</sup>d<sup>-1 </sup>adenine suspension for 28 days. After the model was successfully established， the survival model rats were randomly divided into model group， benazepril group（0.01 g·kg<sup>-1</sup>·d<sup>-1</sup>）and low，medium and high dose of Fushengong prescreption groups （4，8，16 g·kg<sup>-1</sup>·d<sup>-1</sup>）. The normal group and model group were administered the same volume of normal saline by gavage， lasted for 28 days. After the experiment， systolic blood pressure （SBP） and diastolic blood pressure （DBP） of caudal artery were measured， and 24-hour urine was collected to determine 24-hour urine protein （24 h U-pro）. The content of serum creatinine（SCr） and blood urea nitrogen （BUN） in the serum were measured， the histological morphology was observed by hematoxylin eosin（HE）staining， and the degree of renal interstitial fibrosis was observed by Masson staining. Enzyme linked immunosorbent assay （ELISA） was used to determine the contents of AngⅡ， Ang （1-7） and Cystatin C （CysC） in serum and renal homogenate. The protein level of ACE， ACE2， AT1R and MASR were detected by Western blot. The expression of ACE and ACE2 protein in renal tissues were detected by immunohistochemistry. Result:Compared with normal group， the expression levels of SCr， BUN and CysC in model group were significantly increased（<italic>P</italic><0.05）， the content of AngⅡ in serum and kidney tissues were significantly increased， the content of Ang （1-7） were significantly decreased（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues were significantly increased（<italic>P</italic><0.05）， and the expression of ACE2 and MASR protein were significantly decreased（<italic>P</italic><0.05）. Compared with model group and benazepril group， after the intervention with Fushengong prescreption， the serum SCr，BUN and CysC decreased（<italic>P</italic><0.05），the content of AngⅡ in serum and kidney tissues decreased significantly，Ang（1-7） increased significantly（<italic>P</italic><0.05）， the expression of ACE and AT1R protein in renal tissues decreased significantly（<italic>P</italic><0.05）， ACE2 and MASR protein increased significantly（<italic>P</italic><0.05）. The high-dose Fushengong prescreption has the best effect. The high， medium and low-dose effects of Fushengong prescreption were dose-dependent. Conclusion:Fushengong prescreption improved renal function and pathological change of kidney in adenine-induced rats with chronic renal failure. The mechanism may be related to the inhibition of ACE-AngⅡ-AT1R axis and promotion of ACE2-Ang（1-7）-MASR axis ，which leads to the delaying of the progression of chronic renal failure.
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OBJECTIVE：To in vestigate the effects of quercetin （Que）on the expressio n of angiotensin Ⅱ（AngⅡ）-induced myocardial contractile proteins of primary rats through angiotensin-converting enzyme 2-angiotensin-（1-7）-Mas （ACE2-Ang- （1-7）-Mas）axis. METHODS ：Cardiac tissue of rats aged 1-2 d were collected ，and primary cardiomyocytes were isolated and cultured. The gene silencing model of cardiomyocytes ACE2 was constructed. Experiments were divided into 12 groups. Among them，AngⅡ group，AngⅡ+ small interference RNA （siRNA）group，and Ang Ⅱ+ A 779 group were the model groups ；AngⅡ+ losartan group was positive control group ；AngⅡ+Que40 group，AngⅡ+Que80 group，AngⅡ+siRNA+Que40 group，AngⅡ+ siRNA+Que80 group，AngⅡ+A779+Que40 group and Ang Ⅱ+A779+Que80 group were the experimental groups ；blank group and siRNA group were set up. Ang Ⅱ concentration was 1×10－6 mol/L；siRNA final concentration was 50 nmol/L；Que concentration was 40 and 80 μmol/L；A779（Mas receptor inhibitor ）concentration was 1 μmol/L；losartan concentration was 1×10－4 mol/L. mRNA and protein expression of ACE 2，Ang-（1-7） and Mas in primary cardiomyocytes were detected ；the expressions of myocardial contractile proteins were also determined ，such as Na +/Ca2+ exchange channel （NCX），calcium pump （SERCA2a）， phosphoprotein （PLB）. RESULTS ：Compared with Ang Ⅱ group，mRNA expression of Mas was increased significantly in Ang Ⅱ + Que 80 group （P＜0.05）；mRNA expression of ACE2 and Mas were increased significantly in Ang Ⅱ + CZ0210-01） losartan group （P＜0.05）. Compared with Ang Ⅱ group，the 851136165@qq.com protein expression of ACE 2 and Ang- （1-7） were increased significantly in Ang Ⅱ+ Que 40 group（P＜0.05）；compared with Ang Ⅱ + siRNA group ，the protein expression of Ang-（1-7）were increased significantly in Ang Ⅱ+ siRNA+Que 40 group（P＜0.05）；compared with Ang Ⅱ+A779 group，the protein expression of Ang- （1-7）were increased significantly in Ang Ⅱ+A779+ Que 40 group（P＜0.05）. Compared with Ang Ⅱ group，the protein expression of NCX was decreased in Ang Ⅱ+Que40 group（P＜0.05），protein expression of NCX was reduced in Ang Ⅱ+ losartan group （P＜0.05）；compared with Ang Ⅱ+A779 group，the protein expression of NCX was decreased in Ang Ⅱ+A779+ Que80 group （P＜0.05）. CONCLUSIONS ：Que improves the expression of Ang Ⅱ -induced ACE 2-Ang-（1-7）-Mas axis in cardiomyocyte model to some extent ，so as to regulate myocardial contractile protein.
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OBJECTIVE@#Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II.@*METHODS@#HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin (α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence.@*RESULTS@#Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang (1-7) increased the levels of ACE2 and Ang (1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang II.@*CONCLUSION@#Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang (1-7)-Mas axis.
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Animals , Actins , Metabolism , Angiotensin I , Blood , Pharmacology , Therapeutic Uses , Angiotensin II , Blood , Animals, Newborn , Cell Differentiation , Cells, Cultured , Collagen Type I , Metabolism , Disease Models, Animal , Lung , Metabolism , Pathology , Myofibroblasts , Peptide Fragments , Blood , Pharmacology , Therapeutic Uses , Peptidyl-Dipeptidase A , Metabolism , Rats, Wistar , Silicosis , Metabolism , PathologyABSTRACT
AIM:To investigate the effects of exercise training on the progression from prehypertension to hy -pertension,blood pressure regulation and the angiotensin-converting enzyme 2(ACE2)-angiotensin(Ang)(1-7)-MAS axis activation in cardiovascular centers ,and to elucidate the central mechanisms of exercise training postponing hyperten -sion progression.METHODS:The male spontaneously hypertensive rats(SHR;n=20,5 weeks old)and normotensive Wistar Kyoto(WKY)rats(n=20)were randomly assigned to sedentary(Sed)group and exercise training(ExT)group. The trained rats run on a treadmill in moderate-intensity for 20 weeks.Systolic blood pressure(SBP)was measured by tail-cuff method.The baroreflex sensitivity(BRS)was assessed by intravenous injection of phenylephrine.The expression of ACE2 and MAS receptor at mRNA and protein levels in baroreflex centers were determined by real-time PCR and Western blot,respectively.Alterations of BRS were evaluated before and after intracerebroventricular injection of MAS receptor ago -nist Ang(1-7)and its antagonist A779,respectively.RESULTS:Compared with SHR +Sed group,exercise training since prehypertension significantly postponed the development of hypertension ,delayed the hypertension progression ,and decreased SBP in both SHR and WKY rats(P<0.05).Exercise training enhanced blood pressure regulation and improved the BRS in SHR(P<0.01).The expression of ACE2 and MAS receptor at mRNA and protein levels in the baroreflex cen-ters(rostral ventrolateral medulla ,nucleus tract solitarius and paraventricular nucleus )were up-regulated in SHR +ExT group(P<0.05).Central administration of A779 abolished the benefits of exercise-induced improvement of BRS in SHR +ExT group(P<0.01).In contrast,Ang(1-7)improved the BRS in both SHR +Sed group and SHR +ExT group(P<0.05).CONCLUSION:Exercise training postpones hypertension progression and improves blood pressure regula -tion,which may be associated with the activation of central ACE 2-Ang(1-7)-Mas axis.
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The renin angiotensin system(RAS)includes two counterbalance axes:the ACE/Ang Ⅱ/AT1 axis and the ACE2/Ang(1-7)/Mas axis.The RAS can regulate glucose and lipid metabolism in adipose tissue.Most of evi-dences demonstrated that the ACE/Ang Ⅱ/AT1 axis can induce glucose metabolism disorders in adipose tissue, while ACE2/Ang(1-7)/Mas axis improves glucose metabolism.The RAS,which is over activated in obese patient, has been considered to be a potential link among obesity,dyslipidemia and insulin resistance.The effect of ACE/AngⅡ/AT1 axis and ACE2/Ang(1-7)/Mas axis on lipid and glucose metabolism in adipose tissue should be futh-er investigated,and we may find a new target for improving glucose and lipid metabolism.
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We aimed to study the renal injury and hypertension induced by chronic intermittent hypoxia (CIH) and the protective effects mediated by angiotensin 1-7 [Ang(1-7)]. We randomly assigned 32 male Sprague-Dawley rats (body weight 180-200 g) to normoxia control, CIH, Ang(1-7)-treated normoxia, and Ang(1-7)-treated CIH groups. Systolic blood pressure (SBP) was monitored at the start and end of each week. Renal sympathetic nerve activity (RSNA) was recorded. CTGF and TGF-β were detected by immunohistochemistry and western blotting. Tissue parameters of oxidative stress were also determined. In addition, renal levels of interleukin-6, tumor necrosis factor-α, nitrotyrosine, and hypoxia-inducible factor-1α were determined by immunohistochemistry, immunoblotting, and ELISA. TUNEL assay results and cleaved caspase 3 and 12 were also determined. Ang(1-7) induced a reduction in SBP together with a restoration of RSNA in the rat model of CIH. Ang(1-7) treatment also suppressed the production of reactive oxygen species, reduced renal tissue inflammation, ameliorated mesangial expansion, and decreased renal fibrosis. Thus, Ang(1-7) treatment exerted renoprotective effects on CIH-induced renal injury and was associated with a reduction of oxidative stress, inflammation and fibrosis. Ang(1-7) might therefore represent a promising therapy for obstructive sleep apnea-related hypertension and renal injury.
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Animals , Male , Rats , Acute Kidney Injury/drug therapy , Angiotensin I/administration & dosage , Oxidative Stress/drug effects , Peptide Fragments/administration & dosage , Disease Models, Animal , Inflammation/drug therapy , Interleukin-6/metabolism , Kidney/metabolism , Kidney/pathology , Rats, Sprague-DawleyABSTRACT
Objective To reveal the role of serum ACE2/Ang (1-7)in the occurrence of atrial fibrillation (AF)and find new targets for the prevention and treatment of AF by analyzing the correlation between the serum concentration of ACE2/Ang (1-7 )in patients with rheumatic valvular heart disease and the occurrence of AF. Methods We collected the basic clinical information and peripheral venous blood of patients with rheumatic heart valve disease (totally 46 patients,including 24 with AF and 22 with SR).ELISA method was used to detect the serum concentration of ACE2,Ang (1-7)and AngⅡ in the serum samples.Then the differences and correlation between the two groups were analyzed.Results In the AF group ① the diameter of the left atrium was significantly greater than that in the SR group [(60.70±3.08 vs.48.15±2.16)mm,P<0.05];② the serum concentration of AngⅡ was significantly higher than that in the SR group [(45.88±2.87 vs.35.78±1.08)pg/mL, P<0.05],AngⅡ and left atrium diameter were positively correlated (Pearson test,P<0.05);③ the serum concentrations of ACE2 [(7.87±0.74 vs.11.65±0.57)U/L,P<0.05]and Ang (1-7)[(146.05±17.61 vs. 321.71±36.50)pg/mL,P<0.05]were significantly lower than those in the SR group,and negatively correlated with left atrium diameter (Pearson test,P<0.05);④ the serum concentration of Ang (1-7)was negatively correlated with AngⅡ concentration (Pearson test,P<0.05).Conclusion For patients with rheumatic valvular heart disease,ACE2/Ang (1-7 )may play a protective role in the occurrence of AF via antagonizing AngⅡ and inhibiting atrial remodeling.
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Objective To analysis the effects of Ang-(1-7) on the blood brain barrier permeability after subarachnoid hemor-rhage .Methods SAH-rats were produced by two times injection of blood into cisterna magna .Evans blue was used to detect the the permeability of SAH-rats brains and brain water content .RT-PCR and Western blot were performed to measure the expression of adhesion protein ICAM-1 and VCAM-1 in brains of SAH-rats .The artificial hemorrhagic cerebrospinal fluid (BCSF) was used to stimulate vascular endothelial cells (HBMEC) ,and the proliferation and apoptosis of HBMEC cell were analyzed .Results Ang-(1-7) reduced the content of Evans blue and brain water in brains of SAH-rats in dose and time dependent manner with the most sig-nificant change under the treatment of 10 - 5 mol/L Ang-(1-7) for 24 h (P< 0 .05) .Under the above condition ,the mRNA and pro-tein levels of ICAM-1 and VCAM-1 in brains of SAH-rats were significantly up-regulated (P< 0 .05) ,while the content of Evans blue in HBMEC cells stimulated by BCSF was obviously reduced .Besides ,Ang-(1-7) was observed to increase the expression of ICAM-1 and VCAM-1 in BCSF-stimulated HBMEC cells ,enhance the proliferation of HBMEC cells but reduce their apoptosis . Conclusion Ang-(1-7) plays a protective role in the blood-brain barrier damage induced by subarachnoid hemorrhage .
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Objective] To explore the effect of Biejiajian oral Liquid (BOL) on the level of angiotensinⅡ(AngⅡ) and angiotensin(1-7) [Ang(1-7)],and ratio of AngⅡ/Ang(1-7) in liver fibrosis rats. [Methods] Randomly divide male Wistar rats into blank group, model group, BOL groups of high dose and low dose, 10 in each. The model rats were injected with inactivated pig serum abdominally, 0.5mL for each, 2 times/w, for successive 8w. Other rats were injected with the same dosage and period of normal saline. After modeling, administer BOL 10g·kg-1 to low-dose groups rats, and 20g·kg-1 to high-dose group rats; give equal distilled water to blank and model groups, for successive 5 weeks of intragastric administration. The liver histopathology was examined by hematoxylin-eosin(HE) and Masson trichrome staining. Liver and spleen index were calculated. Levels of alanine transaminase(ALT) and aspartate aminotransferase(AST) in serum were assayed by automatic biochemistry detection instrument. Contents of hyaluronic acid(HA), laminin(LN), typeⅢprocollagen(PcⅢ) and type IV collagen(Ⅳ.C) in serum were detected by radioimmunoassay. AngⅡand Ang(1-7) levels were determined by enzyme linked immunosorbent assay. [Results] Compared with model group, the histological injury of liver in rats of BOL groups was relieved; serum levels of AST, ALT, HA, LN, PCⅢ and Ⅳ.C, and the content of AngⅡ in liver homogenate were decreased significantly than that of the model group. Ang(1-7) level was further increased, AngⅡ/Ang(1-7) ratio was decreased obviously in BOL groups. [Conclusion] BOL showed the protective function for hepatic fibrosis, the mechanisms of which may be associated with improvement of Ang(1-7) level, decrease of AngⅡlevel and the ratio of AngⅡand Ang(1-7).
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Objective To observe the members' dynamic change of renin-angiotensin system (RAS) and angiotensin converting enzyme 2(ACE2)-Ang(1-7)-Mas axis during the continuous venovenous hemodiafiltration (CVVHDF) treating the dogs with multiple organ dysfunction syndrome (MODS),and to investigate the efficacy mechanism on cardiac function.Methods Dogs were subjected to hemorrhagic shock plus resuscitation and endotoxemia to establish MODS model,then they were randomly divided into 2 groups:CVVHDF group (n=8) and MODS group (n=6).After endotoxin injection completion,the CVVHDF group received CVVHDF for 12 h,MODS group didn't.Radioimmunoassay,euzymelinked mmunosorbent assay (ELISA) were used to detect the content of renin,Ang Ⅰ,Ang Ⅱ,Ang (1-7).Real-time PCR was used to detect the expression of renin mRNA and ACE2 mRNA.Western blotting was used to detect the protein content of renin,Ang Ⅱ,ACE2 and Ang (1-7).Results (1) Organ function:Compared with the MODS group,the vital signs,heart,lung and renal function were significantly ameliorated in the CVVHDF group,the difference had statistical significance (P＜ 0.05).(2) RAS changes:To detect index from the level of organs,genetic and molecular in arterial tissue,the results displayed that the content of renin,Ang Ⅰ,Ang Ⅱ,the expression of renin mRNA,the protein content of renin,Ang Ⅱ in CVVHDF group were lower than that in MODS group,the difference had statistical significance (P ＜ 0.01).(3)ACE2-Ang(1-7)-Mas axis's changes:Using the same methods above to detect corresponding indicators,the results displayed that the content of ACE2,Ang(1-7),the expression of ACE2 mRNA and the protein content of ACE2,Ang(1-7) in CVVHDF group were significantly improved than that in MODS group,the difference had statistical significance (P ＜ 0.01).Conclusions In the process of CVVHDF treating MODS,the ACE2 -Ang(1-7)-Mas axis plays the role which antagonizes the RAS system,and to protect the cardiac function.This research may be important for MODS' clinical rescue.
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Objective To study the variation of the level of NOS,NO and Ang (1-7) in spontaneously hypertensive rat(SHR).Methods SHR were divided randomly into 3 groups:Bushenyixin group(n=8),valsartan group (n=8),and model group (n=7).Each group was given Bushenyixin tablet,valsartan,and saline by gavage respectively.After 4 weeks,the concentration of NOS,NO,Ang (1-7) in plasma and the concentration of NOS,NO in aorta were be observed.Results The concentration of NO in plasma was significantly lower in the Bushen-Yxin group than for model group(15.500±4.375)μmol/L vs.(26.000±2.828)gmol/L,P＜0.05.The concentration of NO in aorta and Ang1-7 in plasma were significantly higher in the Bushen-Yixin group than in the model group [(35.604±7.505)μmol/L vs.(17.437± 11.649) μ mol/L,(45.542 ± 12.726)ng/L vs.(25.521 ± 2.727) ng/L,P＜0.05].The concentration of NO in aorta was significantly higher in Bushen-Yixin group than in the valsartan group [(21.537± 13.484) μmol/L,P＜0.05].Conclusion Bushen-Yixin tablet had effects of increasing of NO level in aorta and Ang (1-7) level in plasma in spontaneously hypertensive rat.
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0 05] Conclusion Ang (1 7) can exert certain protective effect on renal fibrosis in 2K1C hypertensive rats, and can attenuate proteinuria