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Objective To investigate the effect and mechanism of Imatinib mesilate (Imatinib) on intimal hyperplasia of rabbit carotid arteries after balloon injury. Methods Thirty adult Newzealand rabbits were randomly divided into three groups:group A, B and C. Their right carotid arteries were injuried then administered with 0, 25 or 50 mg/kg of Imatinib dai?ly for 14 consecutive days when the rabbits were sacrificed. The carotid arteries were harvested and sectioned for HE-stain?ing and immunohistochemisty staining. Real-Time PCR was used to examine transcription levels of PDGF-B and PDGFR-βmRNA. The plasma level of PDGF-BB was assayed by ELISA. Results Arterial intimal hyperplasia and stenosis following balloon injury were seen in three groups. Thickness and area of neointima, ratio of thickness of intima to media, ratio of area of intima to media and mRNA level of PDGF-β are all higher in group A than those in group B than those in group C (P<0.01). By contrast, the mRNA transcription level of PDGFR-β increased significantly in group C than that in group A (1.236±0.356 vs 0.708±0.372;t=2.91;P<0.01). Plasma level of PDGF-BB increased in all three groups after balloon injury than that in the baseline (P<0.01). The transcription level of PDGF-BB is higher in group A than that in group B and in group C (ng/L:23.464±3.542, 19.504±2.454, 16.588±1.207, F=17.322, P<0.05). There was no difference between group B and C. There was positive correlation between mRNA transcription level of PDGF-B and plasma level of PDGF-BB ( r=0.806, P<0.01). Conclusion Vascular injury can cause intimal hyperplasia and increased PDGF-B mRNA transcription. Imatinib mesilate could inhibit the intimal hyperplasia through down regulating PDGF-B mRNA transcription.
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Objective To observe the impact of alone or combined use of ezetimibe and simvastatin on transient outward potassium current (Ito) in ventricular myocytes of rat model of ischemia and reperfusion (IR). Methods Seventy-five male SD rats were randomly divided into five groups, control group (CON), control-IR group (CIR), ezetimibe treatment group (EIR), simvastatin treatment group (SIR) and combined ezetimibe and simvastatin treatment group (ESIR). After two weeks of treat?ment with intragastic normal saline or drugs (ezetimibe or simvastatin), myocytes were isolated from right ventricular with colla?genaseⅡ, and Ito was recorded by whole-cell patch clamp technique. Results (1) The Ito current density at+60 mV was sig?nificantly decreased in CIR group than that of CON group (P0.05). The Ito current densities were higher in SIR group and ESIR group compared to those of CIR group. There was no significant difference in Ito current density between SIR group and ESIR group (P>0.05). (2) There was a significant increase in the half-inactivation (V1/2) in CIR group than that of CON group, but no significant differ?ence between EIR group and CIR group (P >0.05). There was a significant difference in the half-inactivation (V1/2) in SIR group and ESIR group compared to that of CIR group (P0.05). There was no significant difference in the slope factor (K) between five groups (P>0.05). (3) The time-con?stant (τ) of Ito recovery curves from inactivation was significantly higher in CIR group than that of CON group (P0.05). There was a significant difference in the time-con?stant (τ) of Ito recovery curves from inactivation in SIR group and ESIR group compared to that of CIR group (P0.05). Conclusion Simvastatin pre-treatment or ezetimibe+simvastatin pre-treatment can reverse the effect of IR on Ito of ventricular myocytes, but ezetimibe shows no such effects.
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Objective To investigate the effects of pioglitazone on atrial ionic channel remodeling in alloxan-induced diabetic rabbit models.Methods A total of 32 rabbits were randomly (random number) divided into control (CN) group,diabetes mellitus (DM) group,diabetes mellitus + pioglitazone 4 mg/ (d · kg) (DPG) group and diabetes mellitus + double pioglitazone 8 mg/ (d · kg) (DPI) group.The diabetic state was examined by quantitative determination of blood glucose levels of ≥ 14 mmol/L.Langendorff-perfused rabbit hearts were used to isolate single atrial myocyte,and whole-cell patch-clamp technique was used to record action potential duration (APD) and atrial ionic channel currents (ICa,L and INa).Variables with normal distribution were compared with One-way ANOVA and LSD-t test.Results Compared with controls,APD90 and APDS0 of left atrial myocytes were significantly prolonged in DM group (P ＜0.05 vs.CN),and there was no significant difference in APD90 frequency adaptation between them (P ＞0.05 vs.CN).The densities of INa were reduced and the densities of ICa,L were increased in DM group (P ＜ 0.01 vs.CN).The above variables were markedly attenuated in DPG and DPI group.Conclusions Pioglitazone may inhibits atrial ionic channel remodeling in diabetic rabbit models.
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Objective To observe effects of angieminⅡ(AngⅡ)and captopril on outward potassium channel currents in canine atrial myoeytes,and to study mechanisnof Ang II and capupril on atrial arrhythmia.Method Ten healthy adult mongrel dogs(general class),weighing 15 to 20 kg,male and female informality,were provided bythe service centre of Tianjin Li-qun experimental animals.Single canine atrial myotcyte was acutely isolated and whole-cell configtmtion of the patch-clamp tchnique was used to detec trapidly activating delayed reefifier outward K+ current(Ikr),slowly activating delayed recti fier outward K+ current(Iks),ultra-rapidly aetivatin delayed rectifier outward K+ current(Ikur)and transient outward potassium current(Ito)before and after An II and captopril peffion.Software of pClamp 7.0 for windows and pClampfit 7.0 Was used to measure current and data were expressed as mean±standard deviation(x±s).SPSS 10.0 statistical was used for statistical analysis.The paired t test was useel for comparison betwn before and after treatment.P<0.05 was comidered as statistical significance.Results AngII(0.5/mol/L)increased Ikr and Iks,ilfibited Ito[(19.54±2.41)pA/pF vs.(24.83±2.52)pA/pF,P=0.001;(20.69±2.29)pA/pF Vfl.(25.59±3.42)pA/pF,P:0.0003;(6.34±1.93)pA/pF vs.(3.71±1.50)pA/pF,P=0.001)],and had no effect on k[(19.78±1.22 pA/pr Vs.(20.39±1.50)pA/pF,P=0.258)].Captopril(5tot/L)had no significant effect on Ikr.,b.k and[(19.11 4-4.91)pA/pF vs.(18.99 4-4.04)-∥pF,P=0.808;(20.76 4-2.89)pA/pF vs.(20.27 a-3.46)pA/pF,P=0.305;(18.50 4-3.78)pA/pF vs.(18.25 4-4.02)pA/pF,P=0.704;(7.31±1.99)pA/pF vs.(6.89±2.12)pA/pF,P=0.136)].Conclusioas AngⅡmay promote atrial electrical remocof atrial fibrillation through outward potassium currents.As angiotemin-eonverting enzy/ne inhibitor.captioruk can prevent atrial electrical rodding of atrial fibrillation by inhibiting renin-angiotensin-system.