RESUMO
OBJECTIVE To compare the efficacy， safety and economy of tacrolimus （TAC）， cyclosporin A （CsA）， cyclophosphamide （CTX） and rituximab （RTX） in the treatment of membranous nephropathy （MN）. METHODS Retrieved from Pubmed， the Cochrane Library， Wanfang data， CNKI and health technology assessment （HTA） official website， HTA reports， systematic reviews/meta-analysis and pharmacoeconomic studies about TAC， CsA， CTX and RTX combined with glucocorticoid in the treatment of MN were collected during the inception and Mar. 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS A total of 15 articles were included， involving 13 systematic reviews/meta-analysis and 2 pharmacoeconomic studies. In terms of efficacy， TAC and CsA showed significant advantages in increasing the response rate， and could improve the levels of urine protein， serum albumin， serum creatinine and serum total cholesterol. In terms of safety， the incidence of adverse reaction induced by TAC， CsA and RTX was low and the symptoms were mild. In terms of economics， CTX cost lower but caused severe adverse reaction； TAC cost higher but showed higher remission rate and good safety. CONCLUSIONS TAC combined with glucocorticoid may be the recommended scheme for MN.
RESUMO
Objective:To construct a geriatric comprehensive health evaluation system, and establish the norm of corresponding score.Methods:The methods of Delphi survey was implemented to develop the geriatric comprehensive health evaluation system.The weight coefficients of the items were calculated and assigned according to the expert-graded importance score and Saaty analytic hierarchy process.Reliability and validity of the system were examined.Goodness of fit was evaluated by confirmatory factor analysis.The demarcation norm of geriatric comprehensive health score was established based on an empirical study of 2, 118 non-hospitalized elderly population.Results:During the process of Delphi expert consultation and item analysis, nine items were deleted and two items were added.In the end, the 29-item comprehensive geriatric health evaluation system was developed, which included three dimensions of physiology, psychology, as well as social support and environment.The Cronbach's α coefficient of the evaluation system was 0.709.The exploratory factor analysis-extracted ten common factors meet ten second-level items.Confirmatory factor analysis indicated that the goodness of fit of the system was good.Geriatric health status was divided into five grades of very poor, poor, general, good and excellent by 0.5 to 1 standard deviation.The demarcation norm of geriatric comprehensive health score for different age and gender was established accordingly.Conclusions:The reliability and validity of the geriatric comprehensive health evaluation system are satisfactory.The construction of comprehensive health evaluation system and the establishment of the norm can facilitate the quantitative assessment of geriatric health status, and provide a reference for the screening and grading of individual health status in the elderly.
RESUMO
OBJECTIVE：To provide method reference for scientifically eva luating the rationality of the use of saxagliptin . METHODS：Based on the drug instructions ，clinical guidelines ，clinical pathways ，related references ，clinical endocrinology department and pharmaceutical experts of a hospital jointly discussed and formulated the evaluation criteria for the rationality of the use of saxagliptin. AHP method was used to assign weights to various indexes of evaluation criteria ；TOPSIS method was used to analyze the use of saxagliptin of 106 cases in the hospital during Nov. 2018-Apr. 2019 retrospectively and evaluate rational drug use. RESULTS ：A total of 6 primary indicators and 12 secondary indicators were established. The first three indicators with a relatively high index weight were indications （with a weight of 0.25），dose and adjustment of administration （with a weight of 0.21）and frequency of administration （with a weight of 0.15）. Among 106 cases，39.6％ of drug use were reasonable ，51.0％ were basically reasonable and 9.4％ were unreasonable. Evaluation results made by weighted TOPSIS were consistent with the actual situation. CONCLUSIONS ：TOPSIS method weighted by AHP is reasonable and feasible for evaluating the rationality of saxagliptin use.
RESUMO
Objective To compare the difference in heart rate variability (HRV)between patients with dementia with Lewy bodies(DLB)and those with Parkinson disease dementia(PDD)and to identify the influencing factors.Methods We retrospectively enrolled 30 patients with DLB(DLB group)and 41 patients with PDD(PDD group)at the outpatient and inpatient services of our hospital from January 2010 to December 2017 in this study,and further recruited 119 normal elderly individuals to serve as the control group.HRV was recorded with 24 h dynamic electrocardiogram and compared between the DLB group and the PDD group.Time domain measures including standard deviation of all normal to normal(NN)intervals(SDNN)and square root of the mean squared differences of successive N N intervals(rMSSD)and frequency domain measures including total power(TP),low frequency(LF),and high frequency(HF)were analyzed with a customized program.The levodopa equivalent dose (LED),mini-mental state examination (MMSE),Montreal Cognitive Assessment (MoCA),Hoehn-Yahr stage(H-Y stage)and the unified Parkinson's disease rating scale Ⅲ (UPDRS Ⅲ),and the Alzheimer's disease Cooperative Study-Activities of Daily Living scale(ADCS-ADL)were assessed in DLB and PDD patients to investigate the influencing factors.Results SDNN,TP,and LF in the DLB group and the PDD group were significantly lower than in the control group (F =14.154,4.742,4.897,P＜0.05).Compared with the control group,rMSSD decreased in the DLB group,but had no significant difference in the PDD group(P＞0.05).The DLB group and the PDD group did not differ in HF from the control group (P ＞ 0.05).There was no significant difference in any HRV indexes between DLB and PDD patients(P ＞0.05).Correlation analysis showed no correlation of HRV with cognitive level(MMSE,MoCA),motor disturbance degree (UPDRS Ⅲ,H-Yahr stage),daily living ability(ADCS-ADL),or dosage of anti-PD drugs (each P ＞ 0.05).Conclusions DLB and PDD patients present similar impairments in autonomic nervous system function,which are not associated with disease severity.
RESUMO
Objective To study the effect of annexin A1 on cardiac function,tumor necrosis factorα(TNF?α),and interleukin 1β(IL?1β)in diabetic rats. Methods Twenty?four SD rats were randomly divided into normal control and diabetic groups. The type 2 diabetes model was in?duced with a high?glucose and high?fat diet and administration of low?dose streptozotocin.Left ventricular end?diastolic volume(LVEDV),left ven?tricular end?systolic volume(LVESV),peak velocity of early diastolic mitral?to?late diastolic peak velocity(e/a)ratio,left ventricular ejection frac?tion(LVEF),and stroke volume(SV)were measured by using color Doppler ultrasonography at the end of week 8. The expression levels of TNF?αand IL?1βin blood were measured by using enzyme?linked immunosorbent assay,and the expression level of annexin A1 in blood was measured at weeks 0,4,and 8 by using real?time polymerase chain reaction. Results Compared with the normal control group,the diabetic group had de?creased LVEDV,e/a,and SV(P<0.05).The annexin A1 expression level in the diabetic group decreased significantly after 8 weeks(P<0.01). The TNF?αand IL?1βlevels in the diabetic group were significantly higher than those in the normal control group(P<0.05)and increased signifi?cantly after 8 weeks(P<0.01). Annexin A1 level correlated with the TNF?αand IL?1βlevels in the diabetic group(P<0.01). Conclusion Annexin A1 expression shows an anti?inflammatory effect that improved the cardiac function of diabetic rats.
RESUMO
Along with detection techniques develop continuously, sensitivity of cardiac troponin (cTn) detection becomes higher and higher.It improves diagnostic rate of patients with acute coronary syndrome,but accompanied by specificity reduction.Therefore, it's necessary to identify non-coronary heart disease that may lead to increase of cTn level.The present article made a review on manifestation of cTn in non-coronary heart disease.
RESUMO
Objective:To investigate current situation of overweight and obesity among population from coastal areas of Fujian province ,and study their correlation with blood pressure (BP) and blood lipids . Methods :A total of 3343≥30 years people from coastal areas of Fujian province were enrolled using cross -sectional survey .Body height and mass ,BP ,waist circumference (WC) ,blood glucose and blood lipids etc .were measured .The correlation among BP ,blood lipids and BMI were statistically analyzed . Results:Detection rates of overweight and obesity were 34.6% and 10.0% respectively .Overweight rate of men was significantly higher than that of women (40.4% vs . 30.7% , P40 years) , P<0.05 or <0.01. Partial correlation analysis indicated that BMI was positively correlated with WC ,SBP ,DBP ,TC ,LDL‐C and HbA1c levels ( r=0.701 ,0.218 ,0.238 ,0.068 ,0.120 , 0.135 ,P<0.01 all) ,and inversely correlated with TG and HDL‐C levels (r= -0.069 both ,P<0.01 both) .Mul‐tifactor linear regression analysis indicated that BMI was significantly correlated with WC ,sex ,age ,DBP ,HDL‐C and FBG levels .After controlling age ,sex and blood glucose etc .,binary Logistic regression analysis indicated that overweight (OR=2.283 ,95% CI 1.915~2.721) and obesity (OR=4.419 ,95% CI 3.329~5.865) were risk fac‐tors for hypertension and dyslipidemia [overweight (OR= 1.356 ,95% CI 1.160~ 1.584) ,obesity (OR= 1.691 , 95% CI 1.319~2.167 )] , P<0.01 all .Conclusion:Prevalence rates of overweight and obesity are high in coastal population in Fujian province .Percentages of hypertension ,dyslipidemia ,DM and cardiovascular risk factor aggre‐gation significantly rise among overweight and obese people ,so controlling body mass is of important significance for prevention and treatment of chronic diseases ,including hypertension ,DM and dyslipidemia etc .
RESUMO
Objective To explore the relationship of serum uric acid level with estimated glomerular filtration rate (eGFR) of elderly patients with hypertention based on a retrospective cohort study.Method The subjects included 465 cases who had a readmission after 3 years of follow-up in an original cohort of 1648 patients with diagnosis of essential hypertension in Fujian Provincial Hospital from August 2007 to September 2009.Multiple regression analysis was performed to examine the effect of serum uric acid level on renal function.Results Four hundred and sixty-five subjects were followed up for an average of 3.9 years.Mean patient age was 68.3 ± 9.7 years.There was no significant difference in uric acid between the baseline and 3 years later (P ＞ 0.05).Multiple regression analysis showed that after adjustment for age,gender,diabetes,body mass index,blood pressure etc,each 100 μmol/L-higher uric acid at baseline was associated with 4.40 ml· min-1· (1.73m2)-1 decrease in eGFR[95％ confidence interval (CI):-6.25--2.55,P ＜ 0.01].According to the alteration of the serum uric acid,all patients were divided into the group with decreased uric acid and the group with increase uric acid.The eGFR was lower in patients with increased uric acid than that in patients with decreased uric acid 3 years later [(70.63±21.54) ml· min-1 · (1.73m2)-1 vs (79.62±21.16) ml· min-1· (1.73 m2)-1,P ＜ 0.01] and there was no significant difference at baseline between the two groups (P ＞ 0.05).Multiple logistic regression analysis showed that after adjusting for aging,gender,diabetes,alteration of blood pressure etc,baseline uric acid was associated with a higher risk for eGFR decreasing more than 10 ml· min-1· (1.73 m2)-1 3 years later [hazard ratio (HR)=2.11,95％CI:1.24-3.59,P ＜ 0.01]; increased uric acid 3 years later resulted in a higher risk for renal function deterioration (HR=2.60,95％ CI:1.67-4.07,P ＜ 0.01).Conclusions Elderly hypertensive patients with baseline hyperuricemia have a lower eGFR,resulting an increased risk of chronic kidney disease.While the patients with declined uric acid had a lesser imparied renal function.It suggests that the improvement of uric acid may help to slow down the deterioration of renal function in elderly hypertensive patients.
RESUMO
[Summary] The basic data and serum targets of 3 349 residents were collected by multi stage stratified cluster random sampling and analyzed by correlation and regression analysis to access its association with cardiovascular risk factors. The result showed that morbidity of hyperuricemia was 18. 85% . The risk of hyperuricemia was raised in people with high triglycerides, high low-density lipoprotein-cholesterol ( LDL-C), low high-density lipoprotein-cholesterol(HDL-C), and low estimated glomerular filtration rate(eGFR). The people with hyperuricemia are usually accompanied with many cardiovascular risk factors.
RESUMO
Objective: To observe the effect of pyridoxamine and telmisartan on the indexes of myocardial remodeling in spontaneous hypertensive rats (SHR). Methods: A total of 48 male SHR at 22 weeks of age were randomly divided into 4 groups:①Hypertension (H) control group, the rats received distilled water 2 ml/d,②telmisartan (T) group, the rats received telmisartan 6 mg/(kg.d),③pyridoxamine (P) group, the rats received pyridoxamine 200 mg/(kg.d),④Combination (TP) group, the rats received both telmisartan and pyridoxamine. All animals were treated for 16 weeks and the systolic blood pressure (SBP) was measured before and after treatment. After treatment, the serum levels of nitric oxide (NO) and super oxide dismutase (SOD) were examined by chemiluminescent method, advanced glycation end-products (AGEs) was detected by ELISA, left ventricular weight index and collagen volume fraction (CVF) in myocardial tissue were calculated, the mRNA expression of myocardial receptor of advanced glycation end products (RAGE) was evaluated by real time RT-PCR. Results: Compared with H group, SBP levels were decreased in T and TP groups,P0.05. Compared with H group, the serum levels of NO and SOD were increased in T, P and TP groups,P<0.01; while compared with T group and P group, the levels of NO and SOD were further increased in TP group,P<0.05. Compared with H group, left ventricular weight index and CVF were decreased in T, P and TP groups,P<0.01; while compared with T group and P group, left ventricular weight index and CVF were further decreased in TP group,P<0.05. Pyridoxamine and telmisartan had the coordinative effect on left ventricular weight index and CVF, P<0.05. The serum levels of AGEs were lower in T group (5.99 ± 0.51) mg/L, P group (5.57 ± 0.91) mg/L and TP group (5.24 ± 0.63) mg/L than that in H group, (6.71 ± 0.50) mg/L,P<0.01; while compared with T group and P group, AGEs was further decreased in TP group,P<0.05. The mRNA expressions of RAGE were reduced in T group (0.035 ± 0.010), P group (0.036 ± 0.005) and TP group (0.024 ± 0.007) than that in H group (0.053 ± 0.010),P <0.01; while compared with T group and P group, the mRNA of RAGE was further reduced in TP group, P<0.05. Conclusion: Pyridoxamine could improve the oxidative stress and the indexes of myocardial remodeling independently from decreasing blood pressure in SHR. Combined intervention of P and T may break the coordination systems between AGEs-RAGE and renin-angiotensin, therefore further improve the indexes of myocardial remodeling in SHR.
RESUMO
Objective To study the relationship between the severity of diastolic heart failure(DHF)and bone mineral density in the elderly. Methods Totally 80 elderly patients aged over 80 years who were tested as normal for cardiac diastolic function by Doppler tissue imaging(DTI) were selected and divided into four groups by the e/a ratio,i.e.,the normal group(n=18),the DHF 1 group(0.8≤e/a<1,n=25),the DHF 2 group (0.6≤e/a<0.8,n=22),and the DHF 3 group(e/a<0.6,n=15). And the other 20 healthy people by physical examination were set as the normal control group.All subjects underwent bone mineral density(BMD)measurement(including femoral neck,total femoral hip and lumbar vertebra 1?4) by dual energy X?ray absorptiometry. Results Bone mineral density(BMD)was significantly decreased(P<0.05)in DHF groups(DHF 1,DHF 2,and DHF 3). Bone mineral density significantly decreased along with the severity of DHF. Bone mineral density was positively correlated with the e/a ratio in the elderly with DHF(r=0.75,P<0.01). Conclusion The severity of diastolic heart failure is closely related to bone mineral density in the elderly. The severity of diastolic heart failure could predict osteoporosis.
RESUMO
Objectives: To explore the relationship between vascular active peptide, apelin level and blood pressure in a coastal population of Fujian province. Methods: A total of 1031 subjects with the mean age of (55.1 ± 10.9) years in a coastal area of Fujian province were included in this cross-sectional study, and 416 subjects with male gender. The questionnaire survey, physical examination and plasma level of apelin measurement were conducted. Based on JNC-7 deifnition of hypertension, the subjects were divided into 3 groups: ① Hypertension group, the patients with systolic blood pressure (SBP)≥140 mmHg and/or diastolic blood pressure (DBP)≥90 mmHg, n=496. ② Pre-hypertension group, SBP at (120-139) mmHg and/or DBP at (80-89) mmHg without medication, n=314.③Normal BP group, SBP283.1 ng/ml, n=257. One way analysis of variance, covariance analysis and multivariate linear regression analysis were used to study the relationship between apelin level and BP. Results: The apelin level in male gender (220.57 ± 78.87) pg/ml was lower than female gender (232.06 ± 81.17) pg/ml. Compared with Normal group, Pre-hypertension group had decreased apelin level, compared with Normal and Pre-hypertension groups, Hypertension group had decreased apelin level, P Conclusion: Apelin level dropping accompanying with BP increasing implies that vascular active peptide, apelin involved in BP regulation.
RESUMO
Objective:To explore changes of central retinal vascular caliber and fractal dimension (Df) and their cor‐relation with blood pressure in hypertensive population .Methods :A total of 2169 subjects>30 years old were en‐rolled in this cross‐sectional study .They were divided into hypertension group (n=819) and non‐hypertension group (n=1350) .Fundus photos were collected in all subjects ,and semi‐automatic software was used to quantitatively ana‐lyze central retinal vascular caliber and Df ,and they were compared between two groups .Results:Compared with non- hypertension group ,there were significant reductions in central retinal arteriolar equivalent [CRAE ,(135.2 ± 10.72) μm vs .(132.25 ± 11.56) μm] ,central retinal venular equivalent [CRVE ,(184.95 ± 16.29) μm vs . (182.52 ± 17.07)μm] and Df [ (1.38 ± 0.05) vs .(1.34 ± 0.05)] in hypertension group , P5 years group was significantly lower than that of ≤5 years group [ (1.33 ± 0.05) vs .(1.35 ± 0.05)] , P<0.01. Conclusion:CARE ,Df are significantly in‐versely correlated to SBP ,DBP and PP in hypertensive population ,while correlation of Df is most .
RESUMO
Objective: To explore the relationship of plasma apelin and angiotensin II (Ang II) with hypertension and hypertension caused early renal damage in order to provide the information for hypertension treatment. Methods: A total of 671 participants were enrolled in this cross-sectional community investigation. All participants were above 30 years of age with local residency longer than 5 years and were divided into 2 groups: Control group,n=354 non-hypertension subjects and Hypertension group,n=317 patients with essential hypertension. The levels of apelin, Ang II, urine creatinine and urinary albumin were examined. The relationship between blood pressure and the ratio of urinary albumin to urine creatinine (UACR) and the relationship between blood pressure and apelin, Ang II were studied by Pearson correlation analysis and multi linear regression analysis. Results: Compared with Control group, Hypertension group had the lower levels of apelin and higher UACR, both P<0.01. The mean arterial pressure (MAP) was negatively related to Ln (apelin), positively related to Ln (Ang II), bothP<0.01. With adjusted gender, age and blood lipids, the above relationship still existed. In Hypertension group, the patients combining with the early renal damage had the lower level of apelin and higher level of Ang II, bothP<0.01. The relevant analysis indicated that Ln (UACR) was negatively related to Ln (apelin), positively related to Ln (Ang II), bothP<0.01. With adjusted gender, age, MAP and blood lipids, the above relationship still existed. Conclusion: The patients with hypertension or hypertension caused early renal damage have decreased apelin. Apelin is negatively related to Ang II, therefore, apelin might be used as a target for hypertension treatment in clinical practice.
RESUMO
Objective:To explore influence of monotherapy or combined use of telmisartan and pyridoxamine on aor-tic remodeling in spontaneously hypertensive rats (SHR)and its possible mechanism.Methods:A total of 48 male SHE were randomly and equally divided into hypertension control group,telmisartan group,group,and telmisartan+ group (combined treatment group). Kyoto Wistar rats of the same age and gender were regarded as normal blood pressure control group (normal control group). Thoracic aortic section were examined by related staining af-ter 16 weeks intervention to calculate the ratio of aortic wall thickness to radius of lumen (Tw/Rl),the ratio of wall area to lumen area (W/L),and the area ratio of media elastic fiber/collagen fiber. Concentrations of related en-zymes and receptor etc. of abdominal aortic were measured.Results:Compared with hypertension control group, there was significant rise in ratio of media elastic fiber/collagen fiber area and significant reduction in media collagen fiber/media area ratio in telmisartan group,pyridoxamine monotherapy group and combined treatment group,and there were significant decrease in Tw/Rl [(0.17±0.02)vs. (0.12±0.01)]and W/L [(0.29±0.03)vs. (0.22± 0.02)]ratios in combined treatment group,P <0.05 or <0.01;immunohistochemistry indicated that there were significant reductions in thoracic aortic receptor of advanced glycation end products (RAGE) [(0.24±0.03)vs.(0.17±0.03)]and extracellular signal-regulated kinase 1/2 (p-ERK1/2 )expression [(0.63 ± 0.06)vs. (0.37± 0.04)]in combined treatment group,P <0.05,<0.01. Fluorescence quantitative PCR indicated that medication can significantly reduce nicotinamide adenine dinucleotide phosphate (NADPH)oxidase subunit p47phox mRNA ex-pression (P <0.01 all),especially in combined treatment group (P =0.001).Conclusion:Combined use of telmis-artan and pyridoxamine is superior to the single use of either drug on improving thoracic aortic remodeling in SHR, the mechanism may be related to it reduces local expression of RAGE and p-ERK1/2 ,and inhibits oxidase subunit p47 of NADPH.
RESUMO
Objective To investigate the association of urinary albumin-to-creatinine ratio (UACR) and the diameter of retinal vessel in population with essential hypertension in Fujian coastal area.Methods Central retinal artery and vein equivalents (CRAE and CRVE) were measured from the avoiding mydriatic digitized photographs and semi-automatic fundus analysis software,as well as albumin and urine creatinine.Results There were significant differences in CRAE levels among the normal control group,normoalbuminuria with essential hypertension group and microalbuminuria with essential hypertension group [(135.68 ± 10.10) μm,(129.79 ± 10.48) μm,(125.29 ± 11.17) μm,all P values ＜0.01].The CRAE levels were significantly negative correlated with UACR (r =-0.29,P ＜ 0.01).Linear regression analysis showed CRAE was associated with UACR in the patients with hypertension(β =-5.0,P ＜ 0.01).Logistic regression analysis showed,systolic blood pressure (β =1.08,P =0.02) was risk factor for CRAE abnormality.The CRAE abnormality was increased in turn in the normal control group,normoalbuminuria with the essential hypertension group and microalbuminuria with essential hypertension group (P ＜ 0.01).Conclusion The reduction of central retinal artery diameter are associated with the hypertensive renal damage.UACR and CRAE could be used to evaluate the microvascular lesions and be used as an indicator to assess the target organs damage in essential hypertension patients.
RESUMO
Objective To investigate the effects and the mechanism of telmisartan and pyridoxamine on oxidative stress in spontaneously hypertensive rats(SHR).Methods SHRs(male,20 weeks of age) were randomly divided into four groups (n＝ 12 for each):hypertension control (HC) group (2 ml of distilled water),telmisartan group[T,6 mg/(kg · d)],pyridoxamine group[P,200 mg/(kg · d)]and combined group(TP,6 mg/kg telmisartan and 200 mg/kg pyridoxamine per day).Treatments were continued for 16 weeks.The normal control group included 13 WKY rats and received gastric lavage with distilled water.SBP of tail artery was measured during the intervention ervey 2 weeks.The levels of AGEs,SOD and MDA were measured by ELISA,xanthine oxidase and thiobarbituric acid methods after the intervention.Expressiones of NF-κBp65,ERK1 and ERK2 in renal tissue were detected by immunohistochemistry.Expression of RAGE in the renal cortex was investigated by Western blot.Results SOD activity was decreased in the HC group.The levels of AGEs,MDA,RAGE and the activations of NF-κBp65 and ERK1/2 were increased in the HC group (t＝4.53,5.52,2.93,al1 P＜0.05).After the 16 weeks' intervention,SOD activity was elevated in T,P and TP groups compared to that in HC group (P＜0.05).The positive expressiones of NF-κBp65,ERK1 and ERK2 were significantly reduced in T,P and TP groups compared to those in HC group (F＝20.13、148.82、18.70,all P＜0.05).All the positive expressiones of NF-κBp65,ERK 1and ERK2 were lowest in the TP group versus T and P groups (t ＝ 3.58、2.84,P ＜ 0.05).Conclusions Telmisartan and pyridoxamine can alleviate the oxidative stress in spontaneously hypertensive rats,which may result from the blocking effect of Ang Ⅱ,the reduction of AGEs-RAGE and inhibiting the signal pathways of ROS,NF-κBp65 and ROS-ERK1/2.
RESUMO
AIM: To investigate the effects of adenovirus-mediated human tissue kallikerin (Ad-hKLK1) gene delivery on the proliferation, migration of VSMC_(SHR) induced by platelet derived growth factor-BB (PDGF-BB). METHODS: The VSMC_(SHR) proliferation induced by PDGF-BB was accessed by cell counting and methyl thiazolyl tetrazoliuin (MTT). The migration was assessed by modified Boyden chamber assay. Western blotting was used to determine the expressions of the cycle-independent kinase inhibitors p27~(Kip1) and p21~(Cip1).RESULTS: Proliferation of VSMC_(SHR) induced by PDGF-BB was inhibited after transfection of Ad-hKLK1 (20-100 MOI) in a MOI-dependent manner. The peak inhibition titer of Ad-hKLK1 fell on 100 MOI, with the peak inhibition rate of 39.3% (cell counting, n=3, P<0.01), 30.2% (MTT, n=3, P<0.01), peak stunning rate of cell-cycle in phase G0/G1 at 36.4%. The inhibitory effects of proliferation and cell-cycle caused by hKLK1 gene delivery were significantly abolished by Hoe140, a bradykinin B2 receptor antagonist. Migration of VSMC_(SHR) induced by PDGF-BB was inhibited after hKLK1 gene delivery, with the peak inhibitory rate of 34.6% (n=6, P<0.01). However the inhibitory effects of migration were not blocked by Hoe140. The protein expression of p27~(Kip1) and p21~(Cip1) increased significantly after the hKLK1 gene delivery, whereas Hoe140 nearly completely blocked these effects (n=3, P<0.01, respectively).CONCLUSION: The hKLK1 gene delivery may inhibit the proliferation and migration of VSMC_(SHR) induced by PDGF-BB. Bradykinin B2 receptor probably mediates the up-regulating expression of p27~(Kip1) and p21~(Cip1) that contributes to the inhibitory effects of proliferation of hKLK1. However, the inhibitory effects of migration by hKLK1 gene delivery may not be mediated by bradykinin B2 receptor.
RESUMO
Objective To explore the effect of resveratrol on the expression of matrix metalloproteinases-9 (MMP-9) in soluble CD40 ligand (sCD40L)-activated macrophages. Methods Human monocytic cell line THP-1 cells under an inducing of phorbol ester differentiated into macrophages. Then the macrophages were sitimulated by sCD40L independently and after a preincubation with resveratrol. The mRNA expression of MMP-9 and tissue-inhibitor of metalloproteinase-1 (TIMP-1) in macrophages were investigated by semiquantitative RT-PCR. The secretions of MMP-9 and TIMP-1 protein were measured by Western blot. The MMP-9 activity was analyzed by gelatin zymography technique. Results The expressions of MMP-9 gene(1.53±0.04 vs. 0.75±0.01,P＜0.05) and protein(244 930.8±31 268.6 vs. 192 976.8±20 223.1,P＜0.05)were higher in macrophages when stimulated by sCD40L. Resveratrol (10 μmol/L and 50 μmol/L)can inhibit the CD40L-induced gene expression and the protein secretion of MMP-9 (P＜0.01). The activity of MMP-9 was degraded by resveratrol (P＜0.05). Meanwhile resveratrol could increase the gene expression and protein secretion of TIMP-1 (P＜0.05). Conclusions Resveratrol can inhibit the CD40L-activated macrophage expression of MMP-9. It may be one of its mechanisms on antiatherosclerosis and stabilization of atheromatous plaques.
RESUMO
ObjectiveTo investigate the effect of resveratrol on the expressions of E-selectin and monocyte chemoattractant protein-1 (MCP-1) in activated endothelial cells.Methods After being pretreated with resveratrol followed by tumor necrosis factor-α (TNF-α) stimulation, human umbilical vein endothelial cells (HUVEC) were randomly divided into three groups: TNF group,resveratrol+TNF-α group and control group. The expression of E-selectin molecule on the surface of HUVEC was detected by flow cytometric analysis and the mRNA expressions of E-selectin and MCP -1 were determined by semiquantitative RT-PCR. ResultsTNF-α induced the expression of E-selectin and MCP-I of HUVEC.Resveratrol (10 μmol/L) inhibited E-selectin expression.The positive cells of E-selectin in TNF group, resveratrol + TNF-α group and control group were(47.84±3.2)%, (15.3±1.7)% and (3.74±1.6)%, respectively, and the differences among the three groups were statistically significant (P<0.05). Conclusions Resveratrol may contribute to the anti-atherosclerotic effect by inhibiting the expression of E-seleetin and MCP-1 of HUVEC.