哮喘小鼠肺脏组织肾素-血管紧张素系统相关组分表达 及AT1R拮抗剂对其影响

目的：探讨肾素-血管紧张素系统（RAS）与哮喘发生的关系，为哮喘发病机制的研究和治疗提供理论依据。方法：复制小鼠哮喘模型，小鼠分为对照组、模型组、坎地沙坦低剂量组及高剂量组，采集小鼠血清，测量血清中血管紧张素Ⅱ (AngⅡ)与血管紧张素Ⅰ(AngⅠ)的含量；通过Western blotting和RT-PCR观察RAS中血管紧张素原(AGT)、血管紧张素转换酶(ACE)、血管紧张素Ⅱ 1型受体（AT₁R）和2型受体（AT₂R）在各组小鼠肺组织中的表达。结果：模型组小鼠血清AngⅡ含量较对照组增高（P<0.05），坎地沙坦组与模型组比较无明显变化（P>0.05）。各组小鼠血清中AngⅠ含量比较差异无统计学意义（P>0.05）。模型组小鼠AT1R和ACE蛋白表达较对照组明显增加（P<0.05），坎地沙坦组AT₁R表达与模型组比较明显降低(P<0.05)，ACE无明显变化（P>0.05）。AT₂R蛋白表达各组间比较差异无统计学意义（P>0.05）。模型组小鼠ACE mRNA表达较对照组明显增加（P<0.05），坎地沙坦组与模型组比较差异无统计学意义（P>0.05）。模型组小鼠AT1R mRNA表达较对照组明显增加（P<0.05），坎地沙坦组较模型组明显降低（P<0.05）。模型组AT2R mRNA较对照组明显降低（P<0.05），坎地沙坦组较模型组明显增加（P<0.05）。各组AGT mRNA表达无明显变化（P>0.05）。  结论：在小鼠哮喘发病过程中，RAS活化参与了哮喘的发病过程，并且AT₁R拮抗剂坎地沙坦可以逆转ACE、AT₁R和AT₂R表达的改变。

Expressions of component of renin - angiotensin system in lung tissue of asthmatic mice and effect of AT1 receptor blocker

Objective To investigate the relationship between the renin-angiotensin system(RAS)and asthma,and provide the theoretical basis for pathogenesis and treatment of asthma.Methods The mouse asthma models were set up and divided into control group,model group,candesartan low-dose group,and candesartan high-dose group.The serum of mice was collected,the levels of serum angiotensin Ⅱ(AngⅡ) and angiotensin Ⅰ(AngⅠ) were detected;the changes of angiotensinogen(AGT),angiotensin-convertion enzyme(ACE),angiotensin Ⅱ type 1 receptor(AT1R) and angiotensin Ⅱ type 2 receptor(AT2R) in the RAS of the mouse lung tissue were delected by Western blotting and RT-PCR.Results The serum Ang Ⅱ level in model group was higher than that in control group(P<0.05),but the level of AngⅡ in candesartan groups had no significant changes compared with model group(P>0.05).The serum Ang Ⅰlevels in each group had no significant changes(P>0.05).The expressions of AT1R and ACE protein in model group were markedly increased compared with control group(P<0.05),the AT1R expressions in candesartan groups were significantly decreased compared with model group(P<0.05),but ACE unchanged.There were no significant differences of the expressions of AT2R protein between various groups(P>0.05).The ACE mRNA expression in model group was increased significantly compared with control group(P<0.05),but there was no significant change in candesartan groups compared with model group(P>0.05).The AT1R mRNA expression in model group was significantly increased compared with control group(P<0.05),the AT1R expressions in candesartan groups were significantly reduced compared with model group(P<0.05).The AT2R mRNA in model group was significantly decreased compared with model group(P<0.05),the expressions in candesartan groups were significantly increased compared with model group(P<0.05).The expression of AGT mRNA in each group had no significant change.Conclusion In the course of asthma of mice,RAS activation is involved in the pathogenesis of asthma,and the AT1R blocker can reverse the changes of the expressions of ACE,AT1R and AT2R.