AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 ...AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.展开更多
AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabet...AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.展开更多
Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of reg...Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.展开更多
The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a...The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.展开更多
Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the r...Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.展开更多
Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing...Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing hearts of hamsters were analysed. Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor （AT1R） mRNA levels were analysed by reverse transcription polymerase chain reaction （RT-PCR）. The activities of chymase and ACE were determined by radioimmunoassay （RIA）. Myocardial collagen fibre analysis was performed under optical microscope. Results Left ventricular systolic pressure （LVSP） and maximum left ventricular developed pressure increase rate （ dp/dtmax, mmHg/s） gradually moved lower at 2, 3,4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure （LVEDP） increased gradually after operation. Compared with the control group （3.55±0. 06, 4.79±0.70）, the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks （4. 28±0. 43, 6. 17±0.73） （P 〈0. 01 ）. Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. ATIR mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group （ P〈0.01 ）, whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks （P〈0.01 ）, respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control（P〈0.01）. Angiotensin Ⅱ （Ang Ⅱ） level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively （P 〈 0. 01 ）. Conclusions A dual Ang Ⅱ forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngⅡ level may be associated with the decrease of ACE activity.展开更多
目的探讨血管紧张素转换酶2(ACE2)对血管紧张素Ⅱ1型受体(AT1R)和细胞外基质激酶(ERK)1/2磷酸化水平及细胞增殖的影响。方法荧光显微镜下观察绿色荧光蛋白(GFP)的表达;将载有ACE2基因慢病毒表达载体(Lentiviral-ACE2)以感染复数为10(MOI...目的探讨血管紧张素转换酶2(ACE2)对血管紧张素Ⅱ1型受体(AT1R)和细胞外基质激酶(ERK)1/2磷酸化水平及细胞增殖的影响。方法荧光显微镜下观察绿色荧光蛋白(GFP)的表达;将载有ACE2基因慢病毒表达载体(Lentiviral-ACE2)以感染复数为10(MOI=10)感染平滑肌细胞不同时间(24、48、72、96 h);采用CCK-8法检测平滑肌细胞增殖;Western blot检测ACE2、AT1R及ERK1/2磷酸化水平。结果目的蛋白GFP表达量明显增加,慢病毒ACE2的表达量成时间依赖性增加,并且在96 h时蛋白表达量较对照组和空载体组明显升高,(1.22±0.06 vs 0.53±0.03和0.53±0.09,P<0.05,n=4);AngⅡ(10-7 mol·L-1)可以促进平滑肌细胞的增殖,ACE2能够抑制AngⅡ诱导的平滑肌细胞增殖(0.53±0.10 vs 0.68±0.03,P<0.05,n=5);AngⅡ(10-7mol·L-1)作用平滑肌细胞12 h后AT1R明显上调,同时ACE2明显抑制AngⅡ诱导的AT1R的上调(0.34±0.01 vs 0.73±0.07,P<0.05,n=4);ACE2能够明显抑制AngⅡ诱导的ERK1/2的磷酸化水平(0.43±0.06 vs 0.71±0.08,P<0.05,n=4)。结论 ACE2可以通过下调AT1R和/及ERK1/2的磷酸化水平而抑制平滑肌增殖,提示ACE2的过表达具有血管保护作用。展开更多
文摘AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.
基金Supported by Biomedical Research Institute Grant(PNU-2013-0373),Pusan National University Hospital
文摘AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.
文摘Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.
基金Supported by CNPq,No.460334/2014-0FAPEMIG,No.CDS-PPM-00555-15(to Simoes e Silva AC)2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation,No.25414(to Miranda AS)
文摘The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.
基金supported by grants from the National Natural Science Foundation of China(No.81102692)the Natural Science Foundation of Hubei Province,China(No.JX6B09)the Fundamental Research Funds for the Central Universities,China(No.2015QN203)
文摘Summary： In order to investigate whether Yinchenhao decoction （YCHD） attenuates hepatic fibro- genesis in the bile duct ligation （BDL） model via recovering and restoring the self-regulation and bal- ance of the renin-angiotensin system （RAS）, 33 specific-pathogen-free （SPF） male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows： G1, the sham group （n=4）; G2, BDL 7-day group （n=5）; G3, BDL＋YCHD 430 mg/mL （n=8）; G4, BDL＋losartan 0.65 mg/mL （ARB group, n=8）; G5, model group （BDL without any treatment, n=8）. YCHD and losartan （10 mL.kgl.day-1） were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respec- tively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin （TBIL）, direct bilirubin （DBIL）, indirect bilirubin （IDBIL）, alanine aminotransferase （ALT）, and aspartate aminotransferase （AST）. Histological changes were ob-. served by transmission electron microscopy （TEM） and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system （RAS） components in- cluding angiotensin converting enzyme （ACE）, angiotensin II type 1 receptor （AT1R）, ACE2, angio- tensin II （Ang II） as well as transforming growth factor 131 （TGF131）. The experimental data were ana- lyzed by principle component analytical method of pattern recognition. The results showed that bio- chemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group （P〈0.05）. Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups （P〈0.05）. Serum AST level in G3 was sig- nificantly lowered than in G5 group （P〈0.05）, but there was no significant difference in ALT among G3, G4 and G5 groups （P〉0.05）. Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression lev- els of ACE2, ACE, Ang II, AT1R and TGF131 in G2, G3 and G4 groups were significantly higher than in sham group （P〈0.05）, and lower than in G5 group （P〈0.05）. However, the differences among G2, G3 and G4 groups were not significant （P〉0.05）. ACE2 protein expression in G3 group was significantly higher than in G2 group （P〈0.05） and there was no significant difference in comparison with G4 group （P〉0.05）. Moreover, the protein expression of TGF131 in G3 group was significantly lower than in G5 and G4 groups （P〈0.05）. Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFI31 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.
基金This investigation was supported by Major National Basic ResearchProgram, People’s Republic of China (973 Program) (No.G2000056904)
文摘Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme （ACE） expressions in the failing hearts of hamsters were analysed. Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor （AT1R） mRNA levels were analysed by reverse transcription polymerase chain reaction （RT-PCR）. The activities of chymase and ACE were determined by radioimmunoassay （RIA）. Myocardial collagen fibre analysis was performed under optical microscope. Results Left ventricular systolic pressure （LVSP） and maximum left ventricular developed pressure increase rate （ dp/dtmax, mmHg/s） gradually moved lower at 2, 3,4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure （LVEDP） increased gradually after operation. Compared with the control group （3.55±0. 06, 4.79±0.70）, the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks （4. 28±0. 43, 6. 17±0.73） （P 〈0. 01 ）. Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. ATIR mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group （ P〈0.01 ）, whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks （P〈0.01 ）, respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control（P〈0.01）. Angiotensin Ⅱ （Ang Ⅱ） level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively （P 〈 0. 01 ）. Conclusions A dual Ang Ⅱ forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngⅡ level may be associated with the decrease of ACE activity.
文摘目的探讨血管紧张素转换酶2(ACE2)对血管紧张素Ⅱ1型受体(AT1R)和细胞外基质激酶(ERK)1/2磷酸化水平及细胞增殖的影响。方法荧光显微镜下观察绿色荧光蛋白(GFP)的表达;将载有ACE2基因慢病毒表达载体(Lentiviral-ACE2)以感染复数为10(MOI=10)感染平滑肌细胞不同时间(24、48、72、96 h);采用CCK-8法检测平滑肌细胞增殖;Western blot检测ACE2、AT1R及ERK1/2磷酸化水平。结果目的蛋白GFP表达量明显增加,慢病毒ACE2的表达量成时间依赖性增加,并且在96 h时蛋白表达量较对照组和空载体组明显升高,(1.22±0.06 vs 0.53±0.03和0.53±0.09,P<0.05,n=4);AngⅡ(10-7 mol·L-1)可以促进平滑肌细胞的增殖,ACE2能够抑制AngⅡ诱导的平滑肌细胞增殖(0.53±0.10 vs 0.68±0.03,P<0.05,n=5);AngⅡ(10-7mol·L-1)作用平滑肌细胞12 h后AT1R明显上调,同时ACE2明显抑制AngⅡ诱导的AT1R的上调(0.34±0.01 vs 0.73±0.07,P<0.05,n=4);ACE2能够明显抑制AngⅡ诱导的ERK1/2的磷酸化水平(0.43±0.06 vs 0.71±0.08,P<0.05,n=4)。结论 ACE2可以通过下调AT1R和/及ERK1/2的磷酸化水平而抑制平滑肌增殖,提示ACE2的过表达具有血管保护作用。
