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［Abstract］Objective:To evaluate the efficacy and safety of fermented cordyceps powder combined with angiotensin-converting enzyme inhibitors （ACEI）/angiotensin Ⅱ receptor blocker （ARB） in the treatment of diabetic kidney disease （DKD）. Method:The randomized controlled trials （RCTs） concerning the treatment of DKD with fermented cordyceps powder plus ACEI/ARB were retrieved from Pubmed， Embase， Cochrane library， China National Knowledge Infrastructure （CNKI）， Chinese BioMedical Literature Database on disc （CBMdisc）， Wanfang Data Knowledge Service Platform， and Chongqing Weipu Database for Chinese Technical Periodicals （VIP）. The quality of the included articles was evaluated by the Cochrane Collaboration's tool， followed by data analysis using RevMan 5.3. Result:A total of 48 RCTs were included， involving 4 562 cases. As revealed by Meta-analysis， the effective rate of fermented cordyceps powder combined with ACEI/ARB was higher than that of ACEI/ARB ［risk ratio （RR）=1.20， 95% confidence interval （CI） （1.15，1.24）， <italic>P</italic><0.000 01］. Moreover， such combination effectively reduced urinary albumin excretion rate ［standardized mean difference （SMD）=-2.61，95%CI （-3.17，-2.05），<italic>P</italic><0.000 01］，24-h proteinuria［SMD=-1.75，95%CI （-2.15，-1.35），<italic>P</italic><0.000 01］， serum creatinine（Scr）［mean difference （MD）=-14.57，95%CI （-17.94，-11.21），<italic>P</italic><0.000 01］， blood urea nitrogen（BUN）［MD=-1.05，95%CI （-1.29，-0.81），<italic>P</italic><0.000 01］， cystatin C （Cys-C） ［MD=-0.52，95%CI （-0.68，-0.36），<italic>P</italic><0.000 01］， fasting blood glucose（FBG）［MD=-0.59，95%CI （-0.93，-0.25），<italic>P</italic>=0.000 6］， hemoglobin A1c（HbA1c）［MD=-0.50，95%CI（-0.75，-0.24），<italic>P</italic>=0.000 1］， tumor necrosis factor-<italic>α</italic>（TNF）-<italic>α </italic>［SMD=-1.68，95%CI （-2.21，-1.15），<italic>P</italic><0.000 01］， C-reactive protein（CRP） ［SMD=-1.35，95%CI （-1.77，-0.93），<italic>P</italic><0.000 01］， and interleukin-6 （IL-6） ［SMD=-1.52，95%CI （-1.98，-1.07），<italic>P</italic><0.000 01］. There was no significant difference in the incidence of adverse events between the two groups ［RR=0.77，95%CI （0.49，1.21），<italic>P</italic>=0.25］. Conclusion:Fermented cordyceps powder combined with ACEI/ARB is more effective than ACEI/ARB in the treatment of DKD， which is worthy of clinical promotion and use. More multi-center RCTs with a large sample size are needed for verification.
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Aim To explore the effects of prenatal caf-feine exposure (PCE) on fetal renal growth retardation and corticosterone on the gene expression of metanephric mesenchyme stem cells.Methods Pregnant Wistar rats were administered with caffeine (30,120 mg ·kg-1) from gestational day 9 to 20.Female fetal kidney samples were collected for morphological observation and gene expression examination.The metanephric mesenchyme stem cells were harvested for cell culture,and renal related genes were detected after the treatment of corticosterone with different concentrations (250,500,1 000 μg · L-1) for 24 hours.Results Compared with the control group,the fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft,accompanied with the repression of the gene expression of glial-cell-line-derived neurotrophic factor/tyrosine kinase receptor (GDNF/c-Ret) signaling pathway.The GDNF/c-Ret signaling pathway and angiotensin Ⅱ receptor type 1 (AT1R)/AT2R expression of metanephric mesenchyme stem cells also decreased in corticosterone groups.Conclusions PCE may induce dysplasia of female fetal kidneys.The potential mechanism is related to the repression of the gene expression of AT1R/AT2R and GDNF/c-Ret signaling pathway by PCE mediated by corticosterone in utero.
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Objective To investigate the effect of the peritoneal lymphatic stomata on intra-abdominal infection and the regulatory mechanism of angiotensin Ⅱ receptor specific inhibitor PD123319 on peritoneal lymphatic stomata.Methods The experimental study was adopted.Forty rats were divided into the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group by the random number table,every group had 10 rats.The classic appendix perforation (CLP) intraabdominal infection model was established in the abdominal infection group.After establishing the model of abdominal infection,PD123319 solution was injected intraperitoneally immediately (0.2 g/kg) in the abdominal infection drug intervention group.Abdominal cavity of the rats in the sham operation group was opened,and then was shut after flipping the intestine.The rats in the control group,sham operation group and intra-abdominal infection group were treated with intraperitoneal injection of 1ml stroke-physiological saline solution.After 2 hours,the rats were sacrificed,and peritoneal tissue was taken for the following tests.(1) The aperture size and distribution density of peritoneal lymphatic stomata were observed by scanning electron microscope (SEM).(2) The nitric oxide (NO) concentration in the peritoneal tissues was detected using nitric oxide nitric acid reduction method.(3) The expressions of endothelial nitric oxide synthase (eNOS) and Phospho-eNOS (P-eNOS) were detected by the Western blot.(4) The intracellular Ca2+ concentration were detect by flow cytometry.Measurement data with normal distribution were presented as-x ± s.The comparison among groups was analyzed using the ANOVA and pairwise comparison was analyzed by the LSD test.Results (1) The aperture size and distribution density of the peritoneal lymphatic stomata in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (2.3 ± 0.4) μm,(2.5 ± 0.5)μm,(4.7 ±0.5)pm,(3.8 ±0.5)pm and (2.0 ±0.8) × 108/m2,(2.1 ±0.7) × 108/m2,(6.2 ± 1.3) × 108/m2,(4.6 ± 1.4) × 108/m2,with statistically significant differences among the 4 groups (F =98.130,56.780,P ＜ 0.05).There were statistically significant differences in the aperture size and distribution density of the peritoneal lymphatic stomata between the intra-abdominal infection group and control group or intra-abdominal infection drug intervention group (t =11.586,8.573,3.854,3.098,P ＜ 0.05) and no statistically significant differences between the control group and sham operation group (t =1.281,0.514,P ＞0.05).(2) The concentrations of NO in the peritoneal tissues in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (0.380 ± 0.024) μmol/gprot,(0.450 ±0.020) μmol/gprot,(1.253 ±0.033) μmol/gprot and (0.579 ±0.035) μmol/gprot,with a statistically significant difference among the 4 groups (F =52.725,P ＜ 0.05).There were statistically significant differences in the concentration of NO between the intra-abdominal infection group and control group or intra-abdominal infection drug intervention group (t =10.536,67.798,P ＜ 0.05) and no statistically significant difference in the concentration of NO between the control group and sham operation group (t =2.007,P ＞ 0.05).(3) The results of Western blot showed that the expressions of eNOS and P-eNOS in the control group,sham operation group,intra-abdominal infection group and intra-abdominal infection drug intervention group were respectively (0.591 ± 0.028)U/mg,(0.603 ± 0.007) U/mg,(0.615 ± 0.027) U/mg,(0.626 ±0.026) U/mg and (0.578 ±0.003)U/mg,(0.603 ± 0.071) U/mg,(0.773 ± 0.033) U/mg,(0.710 ± 0.012) U/mg,with no statistically significant difference in the expression of eNOS among the 4 groups (F =0.902,P ＞ 0.05) and with a statistically significant difference in the expression of P-eNOS among the 4 groups (F =205.062,P ＜ 0.05).There were statistically significant differences in the expression of P-eNOS between the control group and sham operation group or intra-abdominal infection group (t =7.678,13.322,P ＜ 0.05) and between the intra-abdominal infection group and intraabdominal infection drug intervention group (t =4.035,P ＜0.05).(4) The results of flow cytometry showed that Ca2+ concentration in the control group,sham operation group,intra-abdominal infection group and intraabdominal infection drug intervention group were respectively 82.200％ ± 0.060％,81.730％ ± 0.052％,21.980％ ± 0.010％,29.500％ ± 0.004％,showing a statistically significant difference between the 4 groups (F =21 271.030,P ＜ 0.05).There were statistically significant differences in the Ca2+ concentration between the intra-abdominal infection group and control group (t =164.750,P ＜ 0.05) and between the intra-abdominal infection group and intra-abdominal infection drug intervention group (t =21.338,P ＜ 0.05),and no statistically significant difference between the control group and sham operation group (t =1.861,P ＞ 0.05).Conclusion The intra-abdominal infection could increase aperture size and distribution density of peritoneal lymphatic stomata,and PD123319 may be through inhibiting the activation of NO synthase to decrease the concentration of NO,enhance the concentration of Ca2+ in peritoneal mesothelial cells and reduce the opening of peritoneal lymphatic stomata.
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An originate angiotensin Ⅱreceptor-neprilysin inhibitor sacubitril/valsartan with double effect and a new active mode can not only promote the protection of heart and neuroendocrine system , but also inhibit renin-angiotensin-aldosterone system .Sacubi-tril/valsartan is the first and only one conformed by clinical trials with better efficacy when compared with standard therapy drug enala -pril, and its safety is higher as well .Sacubitril-valsartan represents a promising new treatment option for heart failure patients with low-ered risk of cardiovascular death and hospitalization for heart failure .
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Objective To investigate the effects of paeonol on renin-angiotensin system (RAS) occurred on the development of ventricular remodeling after acute myocardial infarction (AMI) in rats. Methods The left anterior descending coronary artery was ligated to establish the model of AMI in male SD rats. Six groups were set up:sham-operation group, AMI model group, captopril control group, paeonol low dose group (6 mg/kg), paeonol middle dose group (9 mg/kg) and paeonol high dose group (12 mg/kg). Rats were given treatment for 4 weeks after the AMI model was established. HE staining was used to observe changes of myocardial tissue. Real-time PCR was used to detect the mRNA levels of angiotensinogen (AGT), angiotensin Ⅱ receptor type1(AGTR1) and endothelin (ET)-1 of six groups. Western blot assay was used to detect the protein levels of peptidyl-dipeptidase A (ACE), angiotensin Ⅱ(Ang)-Ⅱand AGTR1 in six groups. Results The transcription of AGT, AGTR1, ET-1mRNA and the expressions of ACE, Ang-Ⅱ and AGTR1 protein were significantly higher in myocardial tissue of AMI rats than those of sham-operation rats (P＜0.05). Compared with model group, the expressions of AGT, AGTR1, ET-1mRNA and ACE, Ang-Ⅱ, AGTR1 protein were significantly decreased in paeonol high dose group and captopril control group (P＜0.05). Paeonol reduced the expressions of those mRNA and protein levels in a significant dose dependent manner. Conclusion Paeonol can slow down the deterioration of the ventricular remodeling after AMI in rats, which may be related to the inhibition of over-activation of RAS.
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OBJECTIVE:To investigate the status of the use of angiotensin Ⅱ receptor blocker(ARB)in the outpatient of our hospital,and provide reference for the clinical rational drug use. METHODS:Totally 2 460 prescriptions of hypertension treated by ARB drugs in the outpatient of our hospital in 2013 were statistically collected,and the use of such drugs were comprehensively an-alyzed. RESULTS:The ratio of ARB in the treatment of hypertension in the outpatient of our hospital in 2013 was 36.22%,and the common ARB drugs were Irbesartan tablets,Irbesartan and hydrochlorothiazide tablets,Valsartan capsules and Telmisartan tab-lets. The prescriptions of hypertension in our hospital were mostly two-drug combination,the common combination of ARB drugs were ARB+calcium channel blocker(CCB)and ARB+potassium-sparing diuretics;the three-drug combination of ARB drugs were ARB+β-receptor blockers (β-RB)+CCB and ARB+CCB+potassium-sparing diuretics. Among 2 460 prescriptions of hypertension treated by ARB drugs,1 103 prescriptions were irrational,accounting for 44.84%;77 prescriptions were ARB combined with po-tassium-sparing diuretics with no clear indication,accounting for 6.98%;39 prescriptions were ARB combined with ACEI with no clear indication,accounting for 3.54%;330 prescriptions were ARB combined with β-RB with no clear indication,accounting for 29.92%;617 prescriptions had inappropriate frequency of ARB use,accounting for 55.94%;and 40 prescriptions were other irra-tional use,accounting for 3.63%. CONCLUSIONS:ARB drugs are commonly used for hypertension patients in outpatient of our hospital. However,there are still many problems of irrational use in clinical treatment. Therefore,hospital should take appropriate interventions to promote the rational drug use through the joint efforts of physicians,pharmacists and hospitals.
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MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules.They regulate negatively the expression of target genes at post-transcriptional stages by means of affecting the stability of target mRNA or interfering with the transcriptional process.Recently,there is evidence demonstrating that miRNAs play important roles in the gene expressions of thyrotoxic heart diseases.Elevated levels of thyroid hormones profoundly influence the cardiovascular system through the renin-angiotensin system (RAS).As a principal active component of RAS,angiotensin Ⅱ receptor 1 (AT1 R) interacts with miRNAs in promoting or extenuating the progress of thyrotoxic heart disease.In this article,the roles of AT1R-associated miRNAs,miR-21,miR-155,miR-208a/b,and miR-499 in thyrotoxic heart disease were reviewed.
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Objective Through establishing a rat model of atrial fibrillation,to study myocardial angiotensin type Ⅰ (AT1R) and type Ⅱ receptor (AT2R) mRNA expression levels in of the state atrial fibrillation and Artemisia annua extract on its expression.Methods Rat model of atrial fibrillation was established,Artemisia annua extract was used for intervention and captopril was adopted as controls.AT1R,AT2R mRNA and protein expression were observed by PCR and Western-blot technology.Results Compared with the control group (0.36±0.05),myocardial AT1R mRNA expression was significantly increased in the model group (0.84±0.04) (P＜0.05).BothArtemisia annua (0.56±0.03) and captopril (0.53±0.04) could significantly reduce the myocardial AT1R mRNA expression in the atrial fibrillation rats (P＜0.05).Captopril showed obvious AT1R mRNA reduction trend,but there was statistical significance compared with Artemisinic extract (P＞0.05).Artemisinic extract showed no impact on AT2R mRNA expression.Conclusion AT1R was closely related to the incidence of atrial fibrillation.AT1R expression was significantly increased in atrial fibrillation rat.The artemisinic extract can be effectively reduced fibrillation myocardial AT1R expression,which may link with its artemisinic antiarrhythmic mechanism.
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ObjectiveTo evaluate the efficacy and safety of the angiotensin Ⅱ receptor blockers (ARB) in reducing portal hypertension ( PHT) in patients with cirrhosis.Methods PubMed,EMBASE,Web of Science,The Cochrane Central Register of Controlled Trials,Chinese BiomedicalDatabase,ChineseJournals Full-text Database and WanFang Digital Journal Full-text database were searched.Statistical analysis was performed by meta-analysis using RevMan4.2 software.ResultsAmong 8 randomized controlled trials ( RCT) including 282 patients met the inclusion criteria,4 trials were analyzed to compare the ARB with the placebo or no treatment and the other 4 trials were analyzed to compare the ARB with propranolol.Meta-analysis results were as follows.(1) The ARB resulted in more significant hepatic venous pressure gradient ( HVPG) reduction as compared with the placebo or no treatment [ WMD =1.87 mm Hg (1 mm Hg =0.133 kPa),95％CI ( 0.86-2.87 )mmHg,P =0.00003 ].Andthe ARB were similar to propranolol in reducing HVPG [ WMD =0.92 mm Hg,95％ CI ( - 0.41-2.26)mm Hg,P =0.17 ].(2)The ARB led to more significant reduction in mean arterial pressure than the placebo or no treatment [ WMD =8.89 mm Hg,95％ CI( 7.16-10.62)mm Hg,P ＜ 0.00001 ],but they were similar to propranolol had no significant difference.And the ARB had no significant effect on the heart rate of the patients,which was similar to no treatment group ( P ＞ 0.05 ).Whereas,propranolol could greatly decrease heart rate of the patients ( WMD =- 21.25,95％ CI - 25.83-16.68,P ＜ 0.000 01 ).( 3 ) No significant differences were found in serum bilirubin and creatinine levels between the ARB and the placebo or no treatment groups ( P ＞0.05).The rate of nonspecific adverse events was higher in the ARB groups than in the placebo or no treatment groups ( P =0.03 ),but it showed there was no difference between the ARB and propranolol groups (P =0.72).ConclusionThe ARB is effective in reducing portal hypertension in patients with cirrhosis,which is similar to propranolol.Their effects on mean arterial pressure is similar to propranolol without significant effects on hear rate,liver functionand kidney function,and with less nonspecific adverse events.The ARB could become a new choice for the treatment of portal hypertension.
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This study examined the association of polymorphisms in angiotensin Ⅱ receptor genes (AT1R and AT2R) with the risk for aldosterone-producing adenoma (APA) in a Chinese Han population.Four polymorphisms including rs5182 (573T/C) in exon 4,rs5186 (1166A/C) in 3'-untranslated region (3'-UTR) in AT1R gene and rs5194 (2274G/A) in 3'-UTR,rs1403543 (1675G/A) in intron 1 in AT2R gene were detected in 148 APA patients and 192 normal subjects (serving as control) by using a MGB-Taqman probe.The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium (HWE) in the APA and control groups (P＞0.05).The allele A frequency at rs5194 was significantly higher in the APA group (0.49) than in the control group (0.35) (X2=12.08,P=0.001).Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype (OR=2.66,95％ CI=1.45-4.87; OR=1.67,95％ CI=1.02-2.74).Furthermore,rs5194 single-nucleotide polymorphism (SNP) at AT2R gene was significantly associated with APA in additive (OR=1.64,95％ CI=1.21-2.20,P=0.001),dominant (OR=1.94,95％ CI=1.23-3.06,P=0.003),and recessive model (OR=2.01,95％ CI=1.17-3.45,P=0.01).It was concluded that rs5194 polymorphism at AT2R gene was associated with the risk for APA,which may constitute a genetic marker of APA.
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The expression of angiotensin Ⅱ type 1 receptor(AT1R)and angiotensin Ⅱ type 2 receptor (AT2R)in aldosterone-producing adenoma(APA)of the adrenal gland was detected,and their relationship with clinical indexes of APA was analyzed.The mRNA expression of AT1R and AT2R in50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction(RT-PCR).The expression of AT1R and AT2R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry.The expression of AT1R in adenoma,tissues adjacent to tumor,and normal tissues of the adrenal gland showed no significant differences.The expression of AT2R in APA tissue was lower than that in normal adrenal gland tissues(P<0.05).Correlation analysis of the mRNA expression level of AT2R and clinical data from patients demonstrated that AT2R expression was negatively related to plasma aldosterone concentration(PAC)(r=-0.467,P<0.05),but positively related with plasma renin activity(PRA)(r=0.604,P<0.05).It is concluded that down-regulation of the AT2R expression is possibly related with the tumorigenesis of APA.
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Objective To explore the effect of Angiotensin Ⅱreceptor inhibitor on proliferation and apoptosis and cell cycle of human en-dometrial cancer cell line induced by estrogen.Methods Human endometrial cancer cells,ishikawa were cultured,and then treated with different concentrations of estrogen or saralasin.Cell proliferation was examined using MTT,and cell cycle and apoptosis were determined us-ing flow cytometry.Results Saralsin inhibited the proliferation of ishikawa cells.After treated with saralasin at 10 min after estrogen induc-tion,cycle was arrested at G1/G0 phase and S phase was reduced in ishikawa cell with significant difference between treatment group and control group.An increase in early apoptosis and late apoptosis occurred at 10min after treatment.Conclusion Saralsin inhibits endometrial cancer cell ishikawa proliferation,induces apoptosis and accumulation in G1/G0 phase in vitro.Therefore,saralsin may be helpful for the treat-ment of endometrial cancer.
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Objective To explore the effects of estrogen and angiotensin Ⅱ receptor 1 inhibitor（saralasin）on cell proliferation,cell cycle and apoptosis in endometrial carcinoma cell line HEC-1A.Methods Immunocytochemical assay was applied to detect the expression of AT1-R,PI3K,p-Akt and ERK protein in HEC-1A cell.The effects of estrogen and saralasin on cell proliferation,cell cycle distribution and apoptosis of HEC-1A cell were detected by MTT assay and fluorescence activated cell sorting technique.The expression of ERK and p-Akt protein in HEC-1A cell treated with estrogen and saralasin were analyzed by Western blot.Results The expression of AT1-R,PI3K,pAkt,and ERK protein was found in HEC-1A cell.Estrogen stimulated the proliferation of HEC-1A cell,decreased G0~G1 phase proportion and increased S phase proportion significantly,minimized the number of apoptotic cells,and up-regulated the expression of ERK protein.Saralasin obviously inhibited the proliferation and induced apoptosis of estrogen induced HEC-1A cell,increased G0~G1 phase proportion and decreased S phase proportion,and down-regulated the expression of ERK protein.Conclusion Estrogen could promote the proliferation of HEC-1A cell through AT1-R.AT1-R inhibitor saralasin could inhibit the proliferation and induce the apoptosis of estrogen induced HEC-1A cell.The down-regulation of ERK protein expression by interrupting the mitogen-activated protein kinase（MAPK）signaling pathway might be involved in the possible mechanism.Thus saralasin could be a valid approach to treat ER-negative endometrial carcinoma.
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Objective To study the prevalence,treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control.Methods We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female.Hypertension was defined as systolic blood pressure(SBP) ≥ 140 and/or diastolic blood pressure (DBP) ≥90 mm Hg ( 1 mm Hg = 0.133 kPa).Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey.Hypertension control was defined as blood pressure ＜ 140/90 mm Hg before each dialysis session.Results The prevalence of hypertension in the hemodialysis patients was 86.3%.The treatment rate and control rate in those patients were 96.8% and 25.5% respectively.More than half (50.4% ) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more.Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin Ⅱ receptor blockers ( 56.4% ), centrally acting anti-hypertensive agent ( 26.4% ), beta blockers and alpha, beta-blockers( 14.0% ).The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease.The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension.The hypertension control rate elevated significantly with the adequate hemodialysis.Conclusions There is a very high prevalence of hypertension in maintenance hemodialysis patients.Although the treatment rate is high, the control rate is unsatisfactory.So the control of hypertension in hemodialysis patient is still a clinical challenge.Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.
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Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ ) and angiotensin Ⅱ type 1 receptor antagonist (AT1RA) on the transforming growth factor-β1 (TGF-β1) synthesis and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression of in vitro cultured hepatic stellate cells (HSCs). Methods HSC-T6 rat hepatic stellate cell line was selected as the study model of the activated hepatic stellate cells. Cultured HSCs were randomized into control group, Ang Ⅱ group, AT1RA group and Ang Ⅱ AT1RA group. Cell culture medium was used to detect the TGF-β1 level by ELISA method. HSCs were harvested to measure the TIMP-1 mRNA expression by RT-PCR. Results TGF-β1 level of control group, Ang Ⅱ group and AngⅡ AT1RA group in cell culture medium was (7.531 ±0. 654) pg/mL, (9. 855± 1. 485)pg/mL and (7.719 ± 0.329) pg/mL respectively, Ang Ⅱ group higher than control group (P ＜ 0.05 ), Ang Ⅱ AT1RA group lower than Ang Ⅱ group (P ＜ 0. 05 ). TIMP-1 mRNA expression level of control group, Ang Ⅱ group and Ang Ⅱ AT1RA group in HSCs was 3. 387 ± 0. 042, 4.870 ± 0.061 and 3. 837 ± 0. 042 respectively, Ang Ⅱ group higher than control group ( P ＜ 0. 05 ), Ang Ⅱ AT1RA group lower than Ang Ⅱ group (P ＜ 0. 05). Conclusion AngiotensinⅡ can increase the TGF-β1 synthesis and TIMP-1 mRNA expression of hepatic stellate cells, while all these effects are inhibited by angiotensinⅡ type 1 receptor antagonist.
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Angiotensin Ⅱ receptor blockers(ARBs)decrease blood pressure,reverse vascular remodeling,and activate angiotensinⅡsubtype 2(AT2)receptors in order to improve the levels of angiotensinⅡ(AngⅡ),dilate blood vessels,protect against proliferation,and regulate lipid by blocking angiotcnsinⅡtype 1(AT1)receptors.Further understanding the action mech-anism of ARB in neuroprotection may provide a new idea for the treatment of ischemic stroke in clinical practice.
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To evaluate the effect of rosiglitazone on the Angiotensin Ⅱreceptor 1(AT1) and explore its mechanisms of lowering the blood pressure and protecting the organs. The spontaneously hypertensive rats(SHR) 24(SHR)rats were divided into 2 groups:12 were given rosiglitazone,12 were in the control gronp without any treatment. The duration of observation was 8 weeks. The tail blood pressure was measured indirectly.The in situ hybridization and the immunohistochemical methods were used to estimate the expression of the AT1 mRNA and AT1 receptors of heart.In rosiglitazone group,the blood pressure was reduced significantly,and the expressions of AT1 mRNA and AT1 receptor of heart were inhibited.The effect of rosiglitazone on the expressions of AT1 mRNA and AT1 receptor might be one of the reasons why insulin sensilizers reduce the blood pressure and prevent the organ injuries of hypertension.
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Objective To investigate the effects of rapamycin on renal tissue and function of rats with protein overload nephropathy and to explore the protective mechanism of losartan. Methods Experimental rat models with protein overload nephropathy, induced by intraperiotoneal injection of BSA (2. 0 g/d)into female Wistar rats, were divided into three groups: control group, rapamycin group(injected intraperitoneally with rapamycin) and losartan group(injected intraperitoneally with rapamycin and given orally with losartan). At different time points, the quantity of 24-hour urine protein and renal function were measured, and the morphologic changes of renal tissues were evaluated by HE staining and electron microscope. Results Both at day 7 and day 14, rats received BSA developed intense proteinuria. At day 7, compared with control group, 24-hour proteinuria increased markedly in rapamyein group (P<0.05). Nevertheless,proteinufia was notably alleviated in losartan group (P<0.05). At day 14, 24-hour-urine protein of rapamycin group was also significantly higher than that of the losartan group (P<0.05), but therewas no significant difference between control group and losartan group (P>0.05). Proteinuria and intratubular albumin cast formation were alleviated notably in losartan group. The fusion of focal podocytes in rapamycin group was obvious in comparison with control group. Conclusions Rapamycin can agrravate proteinuria in rats with protein overload nephropathy through changing the barrier of glomerular filtration by damaging podocytes. Furthermore, losartan can alleviate severe proteinuria induced by rapamycin.
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OBJECTIVE:To evaluate the clinical utilization of angiotensin Ⅱ receptor blockers(ARBs) in our hospital. METHODS: The clinical utilization data such as the DDDs and consumption sum of ARBs,angiotensin-converting enzyme inhibitors(ACEIs) and calcium antagonists during 2006～2008 in our hospital were evaluated. RESULTS: Both the consumption sum and proportion of ARBs increased year by year,and the DDDs of ARBs increased as well. Irbesartan and telmisartan showed the most rapid increase and losartan potassium took the lead over the three years. CONCLUSION: As a mainstream type of antihypertensive drugs,ARBs get more and more popularity among doctors and patients,and the clinical application of which enjoy a great potential.
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0.05).CONCLUSION:Both group showed approved antihypertensive efficacy,with Coaprovel group showing higher efficacy than in Hyzaar group;and both group showed improvement in allorhythmia.Both group showed low incidences of adverse effect but good tolerance.