姜酮对血管紧张素Ⅱ诱导的心肌成纤维细胞激活的抑制作用  

Inhibitory Effect of Zingerone on the Activation of Cardiac Fibroblasts Induced by Angiotensin Ⅱ

作　　者：王丹[1] 吴青青[1] 唐其柱[1] Wang Dan;Wu Qingqing;Tang Qizhu(Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院心内科,武汉430060

出　　处：《中国药师》2021年第4期636-640,共5页China Pharmacist

基　　金：国家自然科学基金项目(编号:81530012);国家重点研发计划资助项目(编号:2018YFC1311300)。

摘　　要：目的:探讨姜酮对心肌成纤维细胞激活的作用及机制。方法:分离培养原代大鼠乳鼠成纤维细胞,将细胞随机分为对照组、血管紧张素Ⅱ(AngⅡ)刺激组、姜酮不同浓度组(5,50,250,500μmol·L-1)。AngⅡ刺激24 h诱导成纤维细胞活化;MTT法检测细胞活性,CCK8法检测细胞增殖,qPCR法检测细胞胶原的转录情况,荧光染色检测平滑肌肌动蛋白(α-SMA)和Ⅲ型胶原的表达,免疫印迹法检测相关信号分子;丝氨酸/苏氨酸激酶(Akt)抑制剂MK2206抑制Akt的激活(将细胞分为对照组、AngⅡ组和Akt抑制剂组)。结果:各浓度姜酮处理细胞后其细胞活性与对照组比较,差异无统计学意义(P>0.05)。姜酮各浓度组细胞增殖率显著低于AngⅡ组(P<0.05);250μmol·L-1姜酮组Ⅰ、Ⅲ型胶原、α-SMA的表达、磷酸化Akt水平显著低于AngⅡ组(P<0.05)。Akt抑制剂组Ⅲ型胶原和α-SMA的表达与AngⅡ组比较,差异无统计学意义(P>0.05)。结论:姜酮通过抑制Akt活化抑制成纤维细胞激活,可能成为治疗心肌纤维化的新药物。Objective: To investigate the effect and mechanism of zingerone in the activation of cardiac fibroblasts. Methods: Fibroblasts from neonatal rats of primary rats were isolated and cultured. The cells were randomly divided into control group,angiotensinⅡ(AngⅡ) stimulation group and different concentration groups of zingerone(5,50,250 and 500 μmol·L-1). AngⅡ was used to induce fibroblast activation for 24 h. MTT method was used to detect the cell viability. CCK8 method was used to detect the cell proliferation. q PCR method was used to detect the cellular transcription. Fluorescence staining was used to detect smooth muscle actin(α-SMA) and typeⅢ protein levels. Immunoblotting was used to detect related signal molecules. Akt inhibitor MK2206 was used to inhibit Akt activation(cells were divided into control group,AngⅡ group and Akt inhibitor group). Results: There was no significant difference in the cell viability of cells treated with zingerone at various concentrations when compared with the control group(P>0.05). The cell proliferation rate of each concentration group of zingerone was significantly lower than that of AngⅡ group(P<0.05). The expressions of type Ⅰ and Ⅲ collagen,α-SMA and phosphorylated Akt levels in 250 μmol·L-1 zingeron group were significantly lower than those in AngⅡ group(P<0.05). The expressions of type Ⅲ collagen and α-SMA in Akt inhibitor group were not significantly different from those in Ang II group(P > 0.05). Conclusion: Zingerone inhibits cardiac fibroblast activation by inhibiting Akt activation,and may be a new drug for the treatment of cardiac fibrosis.

关 键 词：姜酮 心肌纤维化 心肌成纤维细胞 丝氨酸/苏氨酸激酶 

分 类 号：R965.1[医药卫生—药理学]