摘要
目的探讨血管紧张素转化酶抑制剂卡托普利及血管紧张素Ⅱ(AngⅡ)受体拮抗剂氯沙坦对AngⅡ诱导的肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)表达的干预作用。方法体外原代培养Wistar大鼠主动脉平滑肌细胞,收集不同AngⅡ浓度和作用时间下的细胞和卡托普利组、氯沙坦组和二者联合作用组的细胞,以逆转录(RT)-PCR检测细胞中TNF-α和TGF-β1 mRNA的表达。结果 TNF-αmRNA表达量随AngⅡ浓度和作用时间增加而增加,AngⅡ浓度为10-7、10-6、10-5、10-4 mol/L时表达量分别为(0.43±0.05)、(0.81±0.13)、(0.97±0.17)、(1.09±0.19),与对照组(0.11±0.03)比较,差异有统计学意义(P<0.05或0.01);一定浓度卡托普利(5×10-6mmol/L)、氯沙坦(5×10-6 mmol/L)可明显抑制AngⅡ这一作用;TGF-β1 mRNA表达量随AngⅡ浓度和作用时间增加而明显增加,具有浓度依赖性;在AngⅡ10-7、10-6、10-5和10-4 mol/L时,卡托普利组mRNA表达量分别为(0.19±0.03)、(0.23±0.05)、(0.38±0.14)、(0.34±0.07),较AngⅡ组分别降低了59.57%、73.26%、54.44%和66.67%,差异均有统计学意义(P<0.05或0.01),氯沙坦组分别为(0.17±0.03)、(0.39±0.11)、(0.41±0.12)和(0.39±0.08),较AngⅡ组分别下降了63.82%、54.65%、54.44%和61.76%,差异均有统计学意义(P<0.05)。结论 AngⅡ可促进血管平滑肌细胞TNF-α、TGF-β1 mRNA表达,且有时间和浓度依赖关系;卡托普利、氯沙坦对AngⅡ诱导的血管平滑肌细胞TNF-α、TGF-β1 mRNA表达均有抑制作用,二者联合作用时抑制作用最明显。
Objective To investigate the regulation effects of angiotensin converting enzyme inhibitor captopril and AT1 receptor antagonist losartan on expression of tumor necrosis factor-α（TNF-α） and transforming growth factor-β 1（TGF-β 1） induced by angiotensin Ⅱ（AngⅡ） in vascular smooth muscle cells.Methods Thoracic aortic vascular smooth muscle cells of male Wistar rats were cultured in vitro.The cultured cells were divided in to control group,AngⅡ group,captopril group,losartan group,and captopril combined losartan group.Cells in all groups were collected at the culture end point.TNF-α and TGF-β 1 mRNA expressions in the collected specimens were detected by reverse transcription-PCR（RT-PCR） method,and the effects of AngⅡ on TNF-α and TGF-β 1 mRNA expression and the regulation of captopril and losartan were observed in different AngⅡ concentrations and different stimulating time in vascular smooth muscle cells.Results TNF-αmRNA expression increased with the increment of AngⅡ concentration and the action time（P0.05 or P0.01,except 10-8 mol/L）.Captopril（5×10-6 mol/L） and losartan（5×10-6 mol/L） inhibited the action of AngⅡ（P0.05）.The most significant inhibition action occured when capopril combined with losartan（P0.01）.Inhibition effect of losartan on and TNF-α expression occured later.TNF-α expression was significantly decreased after 72 hours（P0.05）.TGF-β 1 mRNA expression increased with the increment of concentration and the action time of Ang Ⅱ（P0.01）;captopril and losartan decreased the expression of TGF-β 1 mRNA（P 0.05 or P0.01）,especially when the two treatments were combined together.Conclusion AngⅡ increases the expressions of TNF-α and TGF-β 1 mRNA expression in vascular smooth muscle cells,and the expressions increase with the AngⅡ dose and action time.Captopril and losartan inhibit the TNF-α,TGF-β 1 mRNA expressions of vascular smooth muscle cells induced by AngⅡ,and the inhibition is the strongest when losartan is combined
出处
《中国公共卫生》
CAS
CSCD
北大核心
2012年第5期633-636,共4页
Chinese Journal of Public Health
基金
山东省优秀中青年科学家科研奖励基金(2005BS03016)
