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[ABSTRACT]AIM:ToevaluatetheeffectsofantisenseTGF-β1oligodeoxynucleotide(ASTGF-β1)ontheex-pression of TGF-β1 , deposition of extracellular matrix ( ECM) and the neointima formation in the arteries after balloon inju-ry.METHODS:The unmodified and phosphorothioate-modified AS TGF-β1 which containing 15 bases and surrounding the initiation codon region (ATG) of rat TGF-β1 complementary DNA (cDNA) were designed.At the same time, sense TGF-β1 oligodeoxynucleotide ( S TGF-β1 ) with the base sequence complement to AS TGF-β1 was synthesized as a control . The oligodeoxynucleotides were introduced into in vivo and in vitro experiments , respectively .RESULTS:The AS TGF-β1 significantly inhibited the protein expression of TGF-β1 in a concentration-dependent manner , and S TGF-β1 did not have the same effect.Furthermore, no effect of the AS TGF-β1 on the mRNA expression of TGF-β1 in injured VSMCs was ob-served.Moreover, for the injured VSMCs, AS TGF-β1 significantly and concentration-dependently inhibited the basal DNA synthesis.Both AS TGF-β1 and S TGF-β1 did not exhibit dose-dependent effects on DNA synthesis in uninjured VSMCs . Fibronectin ( FN) mRNA expression in injured VSMCs was significantly decreased by AS TGF-β1 in a concentration (0.01~1 μmol/L)-dependent manner .AS TGF-β1 significantly increased the mRNA expression of contractile marker SM 22α, and decreased the mRNA expression of synthetic markers osteopontin and matrix Gla , especially at the concentration of 0.01μmol/L and 0.1 μmol/L.After treatment with AS TGF-β1 (90 μg· kg-1 · d-1 ) for 28 d, the neointima formation was significantly inhibited , and the area ratio of intima/media was markedly decreased by 68% compared with untreated group , but S TGF-β1 had no effect on neointimal formation .CONCLUSION:The AS TGF-β1 specifically inhibits the pro-tein expression of TGF-β1 in the VSMCs derived from injured arteries .Moreover , it significantly inhibits DNA synthesis and cell proliferation, and decreases the expression of FN .Therefore, AS TGF-β1 dramatically attenuates neointima formation after balloon njury .The effects of AS TGF-β1 on the injured VSMCs may be associated with its reverse effects on the altera-tion of VSMC phenotype after balloon injury .
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Objective To investigate the relationship between Atherogenic Index of Plasma(AIP) and the dorsalis pedis artery atherosclerosis in type 2 diabetes. Methods One hundred and twenty-seven patients with type 2 diabetes and 33 healthy individuals were included in the study. The diabetic patients were devided into 2 groups, with( n = 66) or without ( n = 61 ) atherosclerosis. The intima media thickness (IMT) of dorsalis pedis artery were measured by B-mode Doppler ultrasonography. The triglyceride(TG) ,high density lipoproteincholesterol(HDL-C) and other glucolipid metabolic indices were measured in all patients. The AIP was defined as the log value of TG/HDL-C ratio. The one-way ANOVA test was performed to determine the differences among three groups. The relationships between IMT and the other indicators were assessed using Pearson bivariate correlations analysis. The optimal operating point of AIP to diagnose the dorsalis pedis artery atherosclerosis in type 2 diabetes was obtained by drawing ROC curve. Results The AIP value in atherosclerosis diabetic patients,no-atherosclerosis diabetic patients and healthy subjects were 0. 229 ± 0. 132,0. 112 ± 0. 074 and -0. 045 ± 0. 033 respectively. The IMT value were (0. 71 ± 0. 24 ) mm, (0. 49 ± 0. 09 ) mm and (0. 34 ± 0. 15 ) mm respectively. Both indices shown statistical differences among the three groups (Ps = 0. 001 respectively). After adjusting for potential influence factors, AIP showed positive correlation with IMT( r = 0. 315, P = 0. 001 ). The OOP of AIP was 0. 1671 ,the area under the curve was 0. 783. Conclusion AIP was well related to the dorsalis pedis artery atherosclerosis in type 2 diabetes,and the OOP of AIP had good diagnostic reference value in these patients.
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Objective To investigate the expression of angiotensin-converting enzyme 2(ACE2) protein and mRNA in kidney of different age spontaneously hypertensive rats(SHR) and the role of ACE2 in the development of hypertension. Methods Male SHR(n=30) were allocated to 5 groups by age: 1)one-month-old group(S1); 2)two-month-old group(S2); 3)three-month-old group(S3); 4)six-month-old group(S6); 5)nine-month-old group(S9). Sex and age matched Wistar-Kyoto normotensive rats(WKY)served as controls. The expression of ACE2 mRNA in kidney was determined by reverse transcription polymerase chain reaction(RT-PCR). The expression of ACE2 protein in kidney was assessed by immunohistochemistry and computer image analysis. Results 1)An age-dependent increase of SBP was observed in SHR before six months(P0.05). 2)An age-dependent increase of the ACE2 protein and mRNA levels in kidney was observed in both SHR and WKY(P0.05). The ACE2 protein and mRNA levels in kidney were lower in SHR than those in the matched WKY at every corresponding time point(P
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Objective To investigate the role of p38 mitogen-activated protein kinase(p38MAPK) pathway in the proliferation of SHR vascular smooth muscle cells(VSMC) induced by angiotensin Ⅱ(Ang Ⅱ) and platelet-derived growth factor-BB(PDGF-BB).Methods VSMC were obtained from SHR thoracic aorta.DNA synthesis was quantified by measuring [3H]-thymidine incorporation.The p38MAPK activity was evaluated by immunobloting technique with phospho-p38MAPK antibody.Results 1) Ang Ⅱ(10-8-10-6 mol/L),PDGF(3-30 ng/L) dose-dependently increased the proliferation activity of VSMC([3H]-TdR incorporation).Ang Ⅱ(10-7 mol/L) or PDGF(10 ng/L) significantly increased [3H]-TdR incorporation rate in VSMCs(Ang Ⅱ:11 588?1322 vs control 2546?207 counts/min,P
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Objective To investigate if atorvastatin is effective in reducing carotid intima media thickness (CA-IMT) in normocholesterolaemic patients with transient ischemic attack (TIA). Methods Forty-two patients with TIA were recruited. Patients were randomised to receive atorvastatin(5-10 mg/d) or placebo daily. Serum concentration of cholesterol and CA-IMT were measured before randomisation and at 6-and 18-month intervals. Results CA-IMT was significantly lower in atorvastatin group than that in placebo group at 18-month (P
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BACKGROUND: Adriamycin is anthracycline-based drugs of anti-cancer and inhibits many malignant tumors. But due to the large toxicity, it will induce dose-dependent cardiac toxicity, resulting in heart failure in severe case. Compound huangjing oral lipid is against the injury of free radial and is expected to be applied as an assistant therapy for heart failure.OBJECTIVE: To probe into the therapeutic effect of compound huangjing oral lipid and its mechanism on heart failure.DESIGN: Randomized controlled observation was designed.SETTING: Department of Traditional Chinese Medicine , First Affiliated Hospital of Fujian University of Medical Science, Fujian College of Traditional Chinese Medicine.MATERIALS: The experiment was performed in Fujian Research Institute of Hypertension from August 2000 to May 2001, in which, 66 rats were employed and randomized into 6 groups, 11 rats in each one.METHODS: In normal group, physiological saline of equal volume was injected abdominally. In adriamycin group, adriamycin 1mg/kg was injected abdominally on the 2nd and 4th days after experiment, 2 mg/kg was injected on the 6th and 8th days, 3 mg/kg was on the 10th and 12th days and 4 mg/kg was on the 14th and 16th days. The dose was accumulated up to 20 mg/kg in 16 days. In adriamycin+compound huangjing oral liquid 2 mL (small-dose group), adriamycin +compound huangjing oral liquid 4 mL (moderate-dose group) and adriamycin+compound huangjing oral liquid 6ml (large-dose group), the oral lipid of various doses was applied for gastric perfusion everyday successively from the beginning of experiment, in which, the dose of adriamycin was same as adriamycin group. In adriamycin+tebonin group (tebonin group), tebonin 450 mg/kg was administrated once every two days, totally for 8 days, in which, the dose of adriamycin was same as adriamycin group.MAIN OUTCOME MEASURES: To observe the changes of Left ventricular weight and body weight (LVW/BW), α-MHC (myosin heavy-chain)and β-MHC.RESULTS: In the whole experiment, of 66 experimental animals, 5 rats in adriamycin group, 4 rats in small-dose group, 2 rats in moderate-dose group, 3 rats in large-dose group were died from obvious congestive heart failure, finally, 47 rats entered result analysis. Compared with normal group, in adriamycin group, α-MHC was reduced by 20.88% (P ＜ 0.01), β-MHC was increased by 50.93% (P ＜ 0.01) and LVW/BW was increased by 33.83% (P ＜ 0.01). After medication, myocardial β-MHC was transformed to α-MHC; compared with adriamycin group, α-MHC in every medical group was increased (P ＜ 0.01), β-MHC was decreased (P ＜ 0.01) and LVW/BW was decreased of different degrees (P ＜ 0.01 or P ＜ 0.05); among the above-changes, the results in moderate group were the best.CONCLUSION: Compound huangjing oral liquid alleviates toxicity of heart failure induced by adriamycin, probably due to the dose-dependence improvement of the oral liquid in myocardial α-MHC transformation.
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Objective To explore the relationship of pulmonary mycoplasma pneumoniae(MP) infection with acute exacerbated stages of chronic obstructive pulmonary disease(COPD) and community acquired pneumonia(CAP)in the elderly,comparing different serum concentrations of IFN -? ,IL-6,TNF-? in these patients. Methods Serologic analysis through ELISA method was used to detect MP-IgM and MP-IgG to determine the presence of MP and the serum concentrations of IFN-?、IL-6、TNF-? in 30 elderly healthy subjects,39 elderly patients with acute exacerbated stage of COPD and 40 elderly patients with CAP. PCR method was also used to determine the presence of MP from the patients ,sputum. Results (1)The positive rates of MP were much higher in the COPD patients than in the CAP and healthy ones according to PCR or MP-IgM method( P
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Objective To investigate the effects of angiotensinⅡ(AngⅡ), Benazepril(Bena) and Losartan on proliferation and collagen synthesis of cultured rat cardiac fibroblasts(CFb) derived from SHR (CFbSHR) and WKY (CFbWKY). Methods CFb derived from 12-week-old SHR and WKY was cultured by outgrowth of tissue block. Cell proliferation of CFb was determined by direct cell counting .3H-Proline incorporation of CFb was measured after incubation with AngⅡ,Bena and Losartan. Results In serum free(0.4%FCS) medium, cell number of CFb derived from SHR and WKY were not influenced by AngⅡ(10-10mol～10-6mol)and Bena(10-9mol～10-5mol). Increased 3H-proline incorporation wa s induced by AngⅡ in a concentration dependent manner. Benazepril caused an decrease in 3H-Proline incorporation in CFb derived from SHR and WKY. The increased collagen synthesis induced by AngⅡ(10-7mol) was inhibited by Losartan((10-10mol～10-6mol） i n a concentration dependent manner. Conclusion Proliferation of CFb were not influenced by AngⅡ and Bena. Collagen synthesis of CFb was promoted by AngⅡ and inhibited by Bena. Collagen synthesis of CFb in duced by AngⅡ was inhibited by losartan.
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AIM: To investigate the effect of fluvastatin on the proliferation of vascular smooth muscle cells derived from spontaneously hypertensive rats. METHODS: The aorta smooth muscle cells(ASMCs) of spontaneously hypertensive rats were cultured, and proliferation of cells were detected by measuring cell number and -thymidine(-TdR) incorporation after incubation with Ang Ⅱ, PDGF, fluvastatin and mevalonate acid. RESULTS: (1) The increased cell number and -TdR incorporation stimulated with AngII(10 -6 mol/L) and PDGF(10 ?g/L) were significantly inhibited by fluvastatin in a concentration-dependent manner (10 -5 -10 -7 mol/L); (2) The inhibitory effect of fluvastatin was almost completely reversed by mevalonate acid(10 -3 mol/L). CONCLUSION: The proliferation of ASMCs induced by Ang Ⅱ and PDGF was inhibited by fluvastatin, suggesting that mevalonate acid pathway may play an important role in the proliferation of ASMCs.
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Aim To investigate the effects of an angiotensin Ⅱ receptor blocker,candesartan, on aorta oxidative stress-LOX-1 pathway in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP).Methods 12-week-old salt-loaded SHRSP were treated with candesartan(1.0 mg?kg-1?d-1)or a diuretic, trichlormethiazide(TCM,1.6 mg?kg-1?d-1) or no treatment(n=6) in each for 2 weeks. Age-matched salt-loaded WKY rats were served as control(n=6).Systolic blood pressure(SBP)was measured weekly throughout the 2-week period by means of the tail-cuff method.Thoracic aortas were extracted and 24 h urine was collected.NAD(P)H oxidase subunits(p22 phox, p47 phox and gp91 phox)mRNA expression in aorta were assayed by real-time PCR. LOX-1 and type Ⅳ collogen mRNA expression were examined by RT-PCR. gp91 phox and LOX-1 protein expression in aorta were assayed by immunohistochemistry.Urinary albumin excretion was examined by ELISA.Results At the end of the 2nd week, SBP was significantly higher in salt-loaded SHRSP than that in salt-loaded WKY rats. Treatment with candesartan and TCM significantly decreased SBP in salt-loaded SHRSP at similar levels.NAD(P)H oxidase subunits (p47 phox and gp91 phox)and LOX-1 mRNA expression in aorta were markedly higher in salt-loaded SHRSP than those in salt-loaded WKY rats.Candesartan and TCM had the effect of reducing the systolic blood pressure at similar levels. Candesartan significantly down-regulated aorta p22 phox, gp91 phox,LOX-1 and type Ⅳ collogen mRNA expression and decreased urine albumin excretion in salt-loaded SHRSP(P
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AIM: To investigate the effects of fluvastatin on intimal hyperplasia following balloon injury of rabbit iliac artery. METHODS: The iliac arteries of twelve white New Zealand rabbits were injured with an inflated balloon catheter, six rabbits were given fluvastatin 8 mg?kg~-1 ?d~-1 by gavage, the others served as controls. Serum concentrations of endothelin, thromboxane A_2 and prostacyclin were measured by radioimmunoassay at time points before, 3 hours and 3 days after balloon injury. After 28 days, ratio of intima-to-media area (I/M) of the injured arteries were calculated using a computer image analysis system and the alteration of TGF-?_1 and extracellular matrix (FN, LN) were quantified with immunohistochemistry. RESULTS: ① Serum endothelin-1 and thromboxane A_2 significantly increased after injury, whereas serum prostacyclin markedly decreased. The alterations were completely reversed by the treatment with fluvastatin. ② The expression of TGF-?_1 and deposition of ECM in intimal were much lower than that in the untreatment animals. ③ Intimal hyperplasia after balloon injury was significantly attenuated by fluvastatin treatment. CONCLUSION: The inhibitory effects of fluvastatin on intimal hyperplasia after balloon injury may attribute to its inhibiting thrombosis and deposition of ECM. [