目的观察化痰祛浊通络方对自发性高血压大鼠(SHR)血压及一氧化氮(NO)、内皮素1(ET-1)及血管紧张素Ⅱ(AngⅡ)的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0.9...目的观察化痰祛浊通络方对自发性高血压大鼠(SHR)血压及一氧化氮(NO)、内皮素1(ET-1)及血管紧张素Ⅱ(AngⅡ)的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0.9%氯化钠注射液(10 m L/kg)、化痰祛浊通络方组予化痰祛浊通络方水煎液(生药10 m L/kg)、吲达帕胺组予吲达帕胺溶液(10 mg/kg),均每日1次灌服,连续6周。所有大鼠每周测量尾动脉压,给药6周腹主动脉抽血测定血清NO、ET-1及AngⅡ含量。结果给药6周后,化痰祛浊通络方组和吲达帕胺组给药后均可降低SHR收缩压(SP)和舒张压(DP),与空白对照组及本组给药前比较差异均有统计学意义(P<0.05);化痰祛浊通络方组及吲达帕胺组ET-1和AngⅡ含量均较本组给药前及空白对照组明显降低,NO含量明显升高,差异均有统计学意义(P<0.05)。结论化痰祛浊通络方能明显降低SHR血压,其机制可能是通过下调ET、AngⅡ含量及上调NO含量来发挥降压作用。展开更多
To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with...To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.展开更多
Objective To investigate the relationship of four single nucleotide polymorphism （SNP） haplotypes in the angiotensinogen （AGT） gene to the primary hypertension with or without cerebral infarction in the Li nationa...Objective To investigate the relationship of four single nucleotide polymorphism （SNP） haplotypes in the angiotensinogen （AGT） gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China. Methods Total 300 subjects were allocated into three different groups： Groupl, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four poly- morphisms at position - 152 （G-A）, -20 （A-C）, - 18 （C-T）, and -6 （A-G） in the promoter region of AGT. Results The frequen- cies ofCT genotype of AGT-18 and T allele in Group 1 （P = 0.003, P = 0.004） and Group 2 （P = 0.002, P = 0.002） were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group （P = 0.016）, while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 （P = 0.003） compared with the control group, while H5 haplotype frequency which included -20C and -18T was signifi- cantly increased in Group 1 （P = 0.006） versus the control. Conclusion The -20 （A-C） and - 18 （C-T） of the AGT may play an important role in pathogenesis of primary hypertension; and -20 （A-C）, -18 （C-T）, and -6 （A-G） may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Halnan, China.展开更多
Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptorMockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression oftransforming growth factor-β_1 (TGF-β_1) and se...Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptorMockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression oftransforming growth factor-β_1 (TGF-β_1) and secretion of fibronectin, laminin and type Ⅳcollagen from the cultured human mesangial cells . Methods: Human mesangial cells were cultured indifferent glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500 μmol/L) concentrations. The proliferation of mesangial cells were detected at 24, 48 and 72 h . Then the mesangial cellsare divided into four groups, low glucose (5.6 mmol/L) control group, high glucose (30 mmol/L)control group , L158, 809 (10 μmol/L) group and cilazapril (10 μmol/L) group. Forty- eight hourslater, the expression of TGF-β_1 were detected by RT-PCR. Concentrations of TGF-β_1 ,fibronection, laminin and type Ⅳ collagen in the su-pematants of the, mesangial cells weredetermined by EUSA and radioimmunoassay methods. Results: Compared with low glucose control group,the mesangial cells under high glucose medium show excessive proliferation and more TGF-β_1,fibronectin, laminin and type Ⅳ collagen in the supernatant. The expression of TGF-β_1 mRNA wasalso significantly increased under high glucose. The levels of TGF-β_1 and ECM (extracellularmatrix) proteins in the L158, 809 group and cilazapril group are obviously lower than that of thehigh glucose control group. The expression of TGF-β_1 mRNA was markedly decreased in the L158, 809group and cilazapril group compared with that of high glucose control group . Conclusion: Highglucose stimulated the cultured human mesangial cells to excessively proliferate, express TGF-β_1and secrete ECM proteins, and the high glucose-indeced changes were suppressed by either L158, 809and cilazapril.展开更多
Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive di...Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive diabetic patients was searched. The electronic databasesretrieved were Medline (1980 ― 2003), Embase database (1980 ― 2000), Cochrane Library, CL( 1980 ―2004), CBMdisc( 1980 ― 2002), and IPA( 1980 ― 2002). Seven studies were chosen. Data werecombined by Revman 4.2. Results: The pooled effect of change in AER is - 56.31 μg·min^(-1)) [ -81.96, -30.66] (P<0.0001). According to the analysis of subgroups, the pooled effects of 1 - 5 yearsare - 11.97 μg·min^(-1)[-22.04, -1.89] (P = 0.02), -28.01 μg·min^(-1)[-34.50, -21.52](P<0.00001), -43.24 μg·min^(-1) [ -57.15, -29.32] (P< 0.00001), -61.65 μg·min^(-1)[77.77,-45.54] (P< 0.00001), and -98.41 μg·min^(-1)[-162.02,-34.79] (P = 0.002). Regarding progression toclinincal proteinuria as end-point, the pooled Peto OR =0.27 [0.18,0.40] (95% CI), P < 0.00001.According to the analysis of subgroups, the pooled effects of 2 and 5 years are Peto OR = 0.30[0.18,0.51] (P<0.00001) and Peto OR=0.25 [0.13, 0.50](P<0.0001). Publication bias is small.Conclusion In normotensive diabetic patients, ACEI inhibits AER effectively and reduces theprobability of progression of microalbuminuria to clinical proteinuria.展开更多
Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astraga...Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.展开更多
While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endo...While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.展开更多
Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of ...Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.展开更多
文摘目的观察化痰祛浊通络方对自发性高血压大鼠(SHR)血压及一氧化氮(NO)、内皮素1(ET-1)及血管紧张素Ⅱ(AngⅡ)的影响,探讨其降压作用机制。方法将15月龄SHR随机分为空白对照组、化痰祛浊通络方组和吲达帕胺组,每组各9只。空白对照组予0.9%氯化钠注射液(10 m L/kg)、化痰祛浊通络方组予化痰祛浊通络方水煎液(生药10 m L/kg)、吲达帕胺组予吲达帕胺溶液(10 mg/kg),均每日1次灌服,连续6周。所有大鼠每周测量尾动脉压,给药6周腹主动脉抽血测定血清NO、ET-1及AngⅡ含量。结果给药6周后,化痰祛浊通络方组和吲达帕胺组给药后均可降低SHR收缩压(SP)和舒张压(DP),与空白对照组及本组给药前比较差异均有统计学意义(P<0.05);化痰祛浊通络方组及吲达帕胺组ET-1和AngⅡ含量均较本组给药前及空白对照组明显降低,NO含量明显升高,差异均有统计学意义(P<0.05)。结论化痰祛浊通络方能明显降低SHR血压,其机制可能是通过下调ET、AngⅡ含量及上调NO含量来发挥降压作用。
基金National "Ninth five-year" Key Technology R&D Programme of China (Grant No.99-929-01-31)
文摘To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.
基金the Science Foundation of the Health Department of Hainan Province, China （No. 2005-65）.
文摘Objective To investigate the relationship of four single nucleotide polymorphism （SNP） haplotypes in the angiotensinogen （AGT） gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China. Methods Total 300 subjects were allocated into three different groups： Groupl, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four poly- morphisms at position - 152 （G-A）, -20 （A-C）, - 18 （C-T）, and -6 （A-G） in the promoter region of AGT. Results The frequen- cies ofCT genotype of AGT-18 and T allele in Group 1 （P = 0.003, P = 0.004） and Group 2 （P = 0.002, P = 0.002） were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group （P = 0.016）, while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 （P = 0.003） compared with the control group, while H5 haplotype frequency which included -20C and -18T was signifi- cantly increased in Group 1 （P = 0.006） versus the control. Conclusion The -20 （A-C） and - 18 （C-T） of the AGT may play an important role in pathogenesis of primary hypertension; and -20 （A-C）, -18 （C-T）, and -6 （A-G） may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Halnan, China.
基金National Science and Technology Ninth 5-year Project of Medicine(96-906-05-0)
文摘Objective: To explore the effect of L158, 809 (angiatensin Ⅱ receptorMockers, ARBs) and Cilazapril (Angiotensin converting enzyme inhibitor, ACEI) on the expression oftransforming growth factor-β_1 (TGF-β_1) and secretion of fibronectin, laminin and type Ⅳcollagen from the cultured human mesangial cells . Methods: Human mesangial cells were cultured indifferent glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500 μmol/L) concentrations. The proliferation of mesangial cells were detected at 24, 48 and 72 h . Then the mesangial cellsare divided into four groups, low glucose (5.6 mmol/L) control group, high glucose (30 mmol/L)control group , L158, 809 (10 μmol/L) group and cilazapril (10 μmol/L) group. Forty- eight hourslater, the expression of TGF-β_1 were detected by RT-PCR. Concentrations of TGF-β_1 ,fibronection, laminin and type Ⅳ collagen in the su-pematants of the, mesangial cells weredetermined by EUSA and radioimmunoassay methods. Results: Compared with low glucose control group,the mesangial cells under high glucose medium show excessive proliferation and more TGF-β_1,fibronectin, laminin and type Ⅳ collagen in the supernatant. The expression of TGF-β_1 mRNA wasalso significantly increased under high glucose. The levels of TGF-β_1 and ECM (extracellularmatrix) proteins in the L158, 809 group and cilazapril group are obviously lower than that of thehigh glucose control group. The expression of TGF-β_1 mRNA was markedly decreased in the L158, 809group and cilazapril group compared with that of high glucose control group . Conclusion: Highglucose stimulated the cultured human mesangial cells to excessively proliferate, express TGF-β_1and secrete ECM proteins, and the high glucose-indeced changes were suppressed by either L158, 809and cilazapril.
文摘Aim To examine whether AER(albumin excretion rate) in normotensive diabeticpatients can be effectively inhibited by ACEI. Methods Literature on randomized controlled trials ofACEI for inhibiting AER in normotensive diabetic patients was searched. The electronic databasesretrieved were Medline (1980 ― 2003), Embase database (1980 ― 2000), Cochrane Library, CL( 1980 ―2004), CBMdisc( 1980 ― 2002), and IPA( 1980 ― 2002). Seven studies were chosen. Data werecombined by Revman 4.2. Results: The pooled effect of change in AER is - 56.31 μg·min^(-1)) [ -81.96, -30.66] (P<0.0001). According to the analysis of subgroups, the pooled effects of 1 - 5 yearsare - 11.97 μg·min^(-1)[-22.04, -1.89] (P = 0.02), -28.01 μg·min^(-1)[-34.50, -21.52](P<0.00001), -43.24 μg·min^(-1) [ -57.15, -29.32] (P< 0.00001), -61.65 μg·min^(-1)[77.77,-45.54] (P< 0.00001), and -98.41 μg·min^(-1)[-162.02,-34.79] (P = 0.002). Regarding progression toclinincal proteinuria as end-point, the pooled Peto OR =0.27 [0.18,0.40] (95% CI), P < 0.00001.According to the analysis of subgroups, the pooled effects of 2 and 5 years are Peto OR = 0.30[0.18,0.51] (P<0.00001) and Peto OR=0.25 [0.13, 0.50](P<0.0001). Publication bias is small.Conclusion In normotensive diabetic patients, ACEI inhibits AER effectively and reduces theprobability of progression of microalbuminuria to clinical proteinuria.
文摘Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats （6 per group） received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose （10 g material/kg） of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDLC）, high density lipoprotein cholesterol （HDLC）, glucose （GLU） and insulin （INS） levels were measured, respectively, mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index （QUICKI） than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type Ⅱ diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.
文摘While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.
文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.
