哮喘大鼠肺组织中血管紧张素Ⅱ受体和β2肾上腺素能受体表达及缬沙坦的影响
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江苏省高校自然科学研究基金资助(04KJB320089)


The expression of AngiotensinⅡ receptor and β2-adrenergic receptor in the lung of asthmatic rat and their regulation by valsartan.
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    摘要:

    目的:探讨哮喘大鼠肺组织中血管紧张素Ⅱ(AngⅡ)两种受体亚型(AT1R-AT2R)和β2肾上腺素受体(β2-AR)的表达及缬沙坦对两类受体的影响-方法:将50只SPF级Wistar大鼠随机分为正常对照组(A组)-哮喘组(B组)-缬沙坦15 mg/kg组(C1组)-缬沙坦30 mg/kg组(C2组)-缬沙坦50 mg/kg组(C3组)-用10%鸡卵白蛋白(OVA)致敏和1%OVA激发大鼠建立哮喘模型;分别用逆转录-聚合酶链反应(RT-PCR)和Western blot法检测肺组织中ATR和β2-AR mRNA和蛋白表达-结果:与A组相比,B组的AT1R阳性表达率明显增高(P < 0.05)-缬沙坦干预后,C1-C2-C3组的AT1R阳性表达率均明显下降(P均 < 0.05);相关性分析提示AT1R的表达与缬沙坦剂量呈负相关(r = -0.96)-A组未见AT2R表达,B组AT2R表达明显增加-缬沙坦干预后,C1组无AT2R表达,C2-C3组AT2R表达量低于B组(P均 < 0.01)-与A组相比,B组的β2-AR阳性表达率明显下调(P < 0.01),缬沙坦干预后,C1-C2-C3 组的β2-AR阳性表达率均明显上调(P均 < 0.05)-结论:大鼠肺组织中存在血管紧张素Ⅱ受体,并在哮喘发作时被活化,可能参与哮喘发病的病理生理过程-ATR与β2-AR的变化可能存在相关性-哮喘大鼠肺组织中AT1R和AT2R表达增加,β2-AR表达下调-AT1R拮抗剂缬沙坦能抑制AT1R表达,上调β2-AR表达-

    Abstract:

    Objective:To investigate the expression of angiotensinⅡreceptor subtypes(AT1R,AT2R) and β2-adrenergic receptor(AR)in the lungs of asthmatic rats,and the influence of valsartan upon their expression. Methods:Fifty Wistar rats were randomly divided into 5 groups,group A(control),group B(asthma),group C1(Valsartan 15 mg/kg),group C2(Valsartan 30 mg/kg),group C3 (Valsartan 50 mg/kg),each containing 10 subjects. The rats were sensitized by 10% ovalbumin peritoneal injection and challenged by 1% ovalbumin aerosol inhalation to establish the asthmatic model. The levels of AT1R,AT2R and β2-AR mRNA and protein in lung tissues were analyzed by reverse transcriptase-polymerase chain reaction(RT-PCR) and Western blot. Results:Comparing with control (group A),the expression levels of AT1R in asthmatic subjects(group B) was significantly increased(P < 0.05). Valsartan decreased the level of AT1R in asthmatic groups(group C1,C2 and C3). A negative correlation between the expression of AT1R and the dose of valsartan was demonstrated(r = -0.96). There was no AT2R expression in control(group A),while in asthmatic subjects(group B) the AT2R expression increased markably. By use of valsartan,the elevated level of AT2R either could not be found(group C1) or markedly decreased(group C2 and C3); Comparing with control(group A),the β2-AR level in asthmatic subjects(group B) was significantly decreased(P < 0.01). By use of valsartan,the positive expression rate of β2-AR increased in group C1,C2 and C3,compared with group B (P < 0.05,respectively). Conclusion:The results suggested that angiotensin II receptors(ATR) should express in rat lung tissues. The ATR might be activated and play a role in asthma attack. The expression and the function of ATR in the asthmatic rats lung may be related with the change of β2-AR. The expression of AT1R and AT2R in the asthmatic rats lung were increased,while β2-AR decreased. Valsartan could inhibit the expression of AT1R and promote the expression of β2-AR.

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陆国军,王 彤,殷凯生,刘扣英,陈俊娣.哮喘大鼠肺组织中血管紧张素Ⅱ受体和β2肾上腺素能受体表达及缬沙坦的影响[J].南京医科大学学报(自然科学版),2008,28(2):154-157169

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  • 收稿日期:2007-07-17
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