血管紧张素-(1-7)对血管紧张素Ⅱ诱导大鼠系膜细胞增殖与细胞外基质分泌的影响

Influence of angiotensin-(1-7) on proliferation and secretion of cultured rat's glomerular mesangial cells induced by angiotensin Ⅱ

目的探讨血管紧张素-(1-7)[Ang-(1-7)]对血管紧张素Ⅱ(AngⅡ)诱导大鼠系膜细胞(GMC)增殖与细胞外基质分泌的影响。方法在AngⅡ诱导培养的GMC中,应用Ang-(1-7),通过[3H]-Thymidine及[3H]-Leucine掺入分别测定GMC的DNA、蛋白质合成;结晶紫染色检测细胞数目,观察系膜细胞增殖情况;放免法检测细胞培养上清液中Ⅲ型前胶原(PcⅢ)和透明质酸(HA)的含量,观察GMC细胞外基质分泌情况。分别用特异性AngⅡ受体1(AT1)拮抗剂[Sar1,Ile8]-AngⅡ和AngII受体2(AT2受体)拮抗剂PD123319与Ang-(1-7)共同培养,了解Ang-(1-7)的受体特点。结果Ang-(1-7)呈剂量依赖性抑制AngⅡ诱导GMC的DNA、蛋白质合成及细胞数目增加;Ang-(1-7)还能呈剂量依赖性减少系膜细胞PcⅢ和HA的分泌。AT1和AT2受体拮抗剂对Ang-(1-7)的上述作用无影响。结论Ang-(1-7)能抑制基础和AngⅡ诱导的GMC增殖与细胞外基质分泌,该作用不通过AT1和AT2受体介导。

[Objective] To explore the influence of angiotensin-(1-7) [Ang-(1-7)] on proliferation and secretion in cultured rat's Glomerular Mesangial Cells(GMC) induced by Angiotensin-Ⅱ(AngⅡ). [Methods] Ang-(1-7) was used in cultured rats GMC induced by AngⅡ, The synthesis of DNA and protein measured by Incorporation of [3H]-thymidine and [3H]-leucine; cell numbers of rat's GMC were detected by crystal violet, The secretion of PcⅢ and HA was measured by radioimmunoassay in culture medium of rat's GMC. [Results] Ang-(1-7) inhibited synthesis of DNA and protein as well as the secretion of cultured rat's GMC induced by AngⅡ in a dose-dependent manner. Ang-(1-7) also reduced the numbers of cultured rats GMC induced by AngⅡ. The effects of Ang-(1-7) could not be blocked by both [Sar1, Ile8]-AngⅡ, a specific AngⅡAT1 receptor antagonist; and AngⅡAT2 receptor antagonist PD123319. [Conclusion] Ang-(1-7) can inhibit proliferation of cultured rat's GMC induced by AngⅡ, the effects of Ang-(1-7) can not be inhibited by AngⅡAT1 and AT2 receptor antagonist.