姜黄素对血管平滑肌细胞增殖及迁移的影响
Effect of curcumin on proliferation and migration of vascular smooth muscle cells
苏朝江 1刘俪婷 1熊智倩 2张帅 3陈彦 1刘宗旸 1姜燕1
作者信息
- 1. 550003 贵阳,贵州医科大学附属肿瘤医院肾内科
- 2. 贵州医科大学临床医学院
- 3. 550003 贵阳,贵州医科大学附属肿瘤医院实验室
- 折叠
摘要
目的 探讨姜黄素对血管平滑肌细胞(vascular smooth muscle cells,VSMC)异常增殖和迁移的影响及其作用机制.方法 将VSMC分为对照1组,血管紧张素Ⅱ(Angiotensin Ⅱ,AngⅡ)1组,姜黄素1组,姜黄素2组和姜黄素3组(n=11),除对照1组外,其他4组使用AngⅡ建立细胞增殖模型,姜黄素1、2、3组分别给予姜黄素1.5、3.0、4.5 μmol/I)干预,另取VSMC分为对照2组,Ang Ⅱ 2组,姜黄素组和姜黄素+Ang Ⅱ组(n=3).采用Western blot法检测VSMC分化表型蛋白α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、去分化表型蛋白骨桥蛋白(Osteopontin,OPN),自噬相关蛋白(P62、Beclin-1)以及腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)/哺乳动物雷帕霉素靶蛋白(mammaliantargetofrapamycin,mTOR)途径相关蛋白 AMPK、磷酸化 AMPK(p-AMPK)、mTOR、磷酸化 mTOR(p-mTOR)、p70S6K、磷酸化 p70S6K(p-p70S6K)表达水平.结果 AngⅡ 1组VSMC增殖率、迁移率明显高于对照1组(155％vs 100％,66％vs 48％,P＜0.05).与AngⅡ 1组比较,姜黄素2、3组VSMC增殖率以及姜黄素1、2、3组VSMC迁移率明显降低(P＜0.05).与AngⅡ 1组比较,姜黄素2、3组α-SMA表达明显升高,姜黄素1、2、3组OPN表达明显降低(P＜0.05).与对照2组比较,Ang Ⅱ 2组和姜黄素组Beclin-1、p-AMPK/AMPK表达明显升高,P62、p-mTOR/mTOR、p-p70S6K/p70S6K表达明显降低(P＜0.05).与AngⅡ 2组比较,姜黄素组和姜黄素+AngⅡ组Beclin-1、p-AMPK/AMPK表达明显升高,P62、p-mTOR/mTOR、p-p70S6K/p70S6K表达明显降低(P＜0.05).结论 姜黄素能抑制AngⅡ诱导的VSMC增殖及迁移,其作用机制可能与姜黄素激活AMPK/mTOR信号通路增强VSMC的自噬有关.
Abstract
Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.
关键词
姜黄素/肌细胞,平滑肌/细胞增殖/细胞迁移Key words
curcumin/myocytes,smooth muscle/cell proliferation/cell movement引用本文复制引用
出版年
2025
NETL
NSTL
万方数据