摘要
目的 研究固醇调节元件结合蛋白1（SREBP1）在血管紧张素II（Ang II）诱导的血管平滑肌细胞（VSMC）表型转化中的作用。方法 将C57BL/6J小鼠分为对照组、处理组1（150 ng/kg/min Ang II）、处理组2（300 ng/kg/min Ang II）、处理组3（600 ng/kg/min Ang II）和缬沙坦组（600 ng/kg/min Ang II＋40 mg/kg/d 缬沙坦）处理28 d。观测小鼠血压和动脉血管变化。实时荧光定量PCR和免疫印迹检测血管SREBP1的表达。将VSMC分为正常组、处理组1 （0.1×10-6 mol/L Ang II）、处理组2（0.5×10-6 mol/L Ang II）、处理组3（1×10-6 mol/L Ang II）、缬沙坦组（1×10-6 mol/L Ang II＋1×10-6 mol/L 缬沙坦）、LY294002组（1×10-6 mol/L Ang II＋10 ng/mL LY294002）、沉默对照组（1×10-6 mol/L Ang II＋scramble siRNA）、沉默组（1×10-6 mol/L Ang II＋SREBP1 siRNA）处理，免疫印迹检测细胞SREBP1、Akt、磷酸化Akt（p-Akt）、α平滑肌肌动蛋白（α-SMA）、骨桥蛋白（OPN）的表达。 结果 与对照组比较，Ang II处理组小鼠收缩压和舒张压明显升高，缬沙坦组与处理组比较血压降低。相比于对照组，处理组小鼠血管壁增厚、管腔增大，缬沙坦处理则抑制血管重塑。Ang II处理组小鼠主动脉血管SREBP1 mRNA和蛋白表达水平高于对照组和缬沙坦组。SREBP1、磷酸化Akt、OPN在处理组VSMC细胞中表达水平高于正常组，而在缬沙坦组、LY294002组和沉默组中低于处理组；α-SMA在处理组中表达降低，而在缬沙坦组、LY294002组和沉默组中升高。 结论 Ang II通过活化PI3K/Akt/SREBP1通路调控VSMC表型转化、诱导小鼠动脉血管重塑。
Objective To investigate the function of sterol regulatory element-binding protein 1 （SREBP1） in phenotypic transition of vascular smooth muscle cells （VSMC） induced by angiotensin Ⅱ （Ang Ⅱ ）. Methods C57BL/6J mice were randomly allocated into control group, treatment group 1 （150 ng·kg-1min-j Ang Ⅱ ）, treatment group 2（300 ng·kg-1·min-1Ang Ⅱ ）, treatment group 3（600 ng·kg-1·min-1 Ang Ⅱ ） and Valsartan group （600 ng·kg-1·min-1 Ang Ⅱ ＋40 mg·kg-1·d-1 Valsartan） and treated for 28 d. Variation of aortic blood pressure and vessel were observed. Vascular SREBP1 mRNA and protein expression was analyzed by qRT-PCR and Western blot. VSMC were divided into normal group, treatment group 1（0.1~10-5 mol/L Ang Ⅱ ）, treatment group 2（0.5x 104 mol/L Ang Ⅱ ）, treatment group 3（ 1.0× 104 mol/L AngⅡ ）, Valsartan group（ 1.0× 10-6 mol/L Ang Ⅱ ＋ 1.0×10-6 mol/L Valsartan）, LY294002 group （1.0×10-6 mol/L AngⅡ＋10 ng/mL LY294002）, mock group （1.0× 104 mol/L Ang Ⅱ ＋scramble siRNA）, and knockdown group （1.0×10-6 mol/L Ang Ⅱ ＋SREBP1 siRNA）. The expression of SREBP1, Akt, phosphorylated Akt（p-Akt）, orsmooth muscle actin（α-SMA ） and osteopontin（OPN ） in VSMC was analyzed. Results Compared with control group, the systolic pressure and diastolic pressure in Ang I1 treated mice were enhanced, while the blood pressure in Valsartan group was decreased in comparison with treatment groups. Compared with the control, vascular wall thickness and lumen enlargement were induced in mice of treatment group, whereas Valsartan alleviated vascular remodeling. The expression of SREBP1 mRNA and pro- tein was higher in the aorta of Ang Ⅱ treated mice than that in the control and Valsartan treated mice. The ex- pression of SREBP1, p-Akt, and OPN in VSMC of treatment groups was augmented compared with normal group, while they were downregulated in VSMC of valsartan group, LY294002 group, and knockdown group when com- pared with treatment groups, α-SMA expression was decreased in treatment groups and increased in Valsartan group, LY294002 group, and knockdown group. Conclusion Ang Ⅱ regulates VSMC phenotypic transition and aorta vascular remodeling through activating PI3K/Akt/SREBP1 pathway.
出处
《中国心血管病研究》
CAS
2018年第1期79-83,I0001,I0002,共7页
Chinese Journal of Cardiovascular Research
关键词
高血压
血管平滑肌细胞
固醇调节元件结合蛋白1
血管紧张素Ⅱ
表型转化
Hypertension
Vascular smooth muscle cells
Sterol regulatory element-binding protein 1
Angiotensin Ⅱ
Phenotypic transition
