鹿角方阻断PI3K/AKT信号通路对AngⅡ诱导心肌细胞肥大的保护作用  

Lujiao Formula attenuates cardiac hypertrophy induced by AngⅡthrough blocking PI3K/AKT signaling pathway

作　　者：张建伟[1] 刘力[2] ZHANG Jian-wei;LIU Li(Shuguang Hospital Attached to Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China)

机构地区：[1]上海中医药大学附属曙光医院药学部,上海200021 [2]上海中医药大学附属曙光医院,上海200021

出　　处：《中华中医药杂志》2021年第2期732-736,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81573648);国家科技重大专项(No.2010ZX09102-208);上海中医药大学附属曙光医院四明基金(No.SGKJ-201711)。

摘　　要：目的:研究鹿角方对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的乳鼠心肌细胞肥大的保护作用,并从PI3K/AKT信号通路的角度探讨其可能机制。方法:培养原代乳鼠心肌细胞,将其随机分为正常对照组、AngⅡ模型组、鹿角方+AngⅡ组、LY294002(PI3K通路阻断剂)+AngⅡ组、鹿角方+LY294002+AngⅡ组。通过图像分析系统测量心肌细胞表面积;RT-PCR检测ANP、BNP mRNA表达;Wertern Blot检测PI3K、p-PI3K、AKT、p-AKT(Ser473)和GSK3β蛋白表达。结果:与正常对照组比较,AngⅡ模型组心肌细胞表面积、ANP和BNP mRNA表达以及p-PI3K和p-AKT(Ser473)蛋白表达显著增加(P<0.01);而鹿角方可显著抑制AngⅡ诱导的心肌细胞肥大,使模型细胞表面积显著减小(P<0.01),ANP、BNP mRNA表达以及p-PI3K和p-AKT(Ser473)蛋白表达显著降低(P<0.01),且抑制效果与LY294002相当,而鹿角方对GSK3β蛋白表达无显著影响。结论:鹿角方可显著抑制AngⅡ诱导的心肌细胞肥大,其机制与阻断PI3K/AKT信号通路有关。Objective:To evaluate whether Lujiao Formula could protect against neonatal rat cardiomyocyte hypertrophy induced by angiotensin I(Ang I),and to define the underlying molecular mechanisms from PI3 K/AKT signaling pathway.Methods:The neonatal rat cardiomyocyte were cultured in vitro and randomly divided into the control group,the Ang I model group,the Ang I+Lujiao Formula group,the LY294002(PI3 K inhibitor)+Ang I group,and the Lujiao Formula+LY294002+Ang I group.The cell surface area was measured by image analysis system.RT-PCR was used to test the mRNA levels of atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP).Western Blot analysis was used to assay the phosphorylation level of PI3 K,p-PI3 K,Akt,p-AKT(Ser473)and GSK-3βproteins.Results:Compared with the normal control group,the surface area,the expression of ANP and BNP mRNA,the expression of p-PI3 K and p-AKT(Ser473)protein of cardiomyocytes treated with Ang I respectively significantly increased(P<0.01).Lujiao Formula could significantly inhibit Ang I induced cardiomyocyte hypertrophy.Lujiao Formula could decrease the surface area of cardiomyocytes treated with Ang I(P<0.01),Lujiao Formula could reduce the expression level of ANP,BNP,p-PI3 K and p-AKT(Ser473)(P<0.01).The inhibition effect of Lujiao Formula was similar to that of PI3 K/AKT signaling pathway inhibitor LY294002.Lujiaofang could not significantly influence the expression level of GSK3β.Conclusion:Lujiao Formula could significantly protect against neonatal rat cardiomyocyte hypertrophy induced by Ang II,by inhibiting the PI3 K/AKT signaling pathway.

关 键 词：鹿角方 心肌肥大 血管紧张素Ⅱ PI3K/AKT信号通路 

分 类 号：R285.5[医药卫生—中药学]