氟伐他汀对血管紧张素Ⅱ诱导的心肌成纤维细胞增殖、迁移和侵袭的影响  

Effects of fluvastatin on proliferation, migration and invasion of cardiac fibroblasts induced by angiotensin Ⅱ

作　　者：杨萍 代天 庄红[1] 蒋品 赵谦 张苏川[1] YANG Ping;DAI Tian;ZHUANG Hong;JIANG Pin;ZHAO Qian;ZHANG Su-chuan(Department of Cardiovascular Medicine,Affiliated Hospital of Jianghan University/Wuhan No.6 Hospital,Wuhan 430015,Hubei Province,China)

机构地区：[1]江汉大学附属医院、武汉市第六医院心血管内科,湖北武汉430015

出　　处：《中国临床药理学杂志》2022年第2期103-107,102,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的探讨氟伐他汀对血管紧张素Ⅱ(AngⅡ)诱导的心肌成纤维细胞(CFs)增殖、迁移、侵袭的影响及其作用机制。方法将CFs随机分为A、B、C、D、E、F、G、H、I、J和K组。A组未给予氟伐他汀和AngⅡ处理;B组用0.1μmol·L^(-1)AngⅡ刺激细胞6 h;C、D、E组在0.1μmol·L^(-1)AngⅡ刺激细胞6 h后,再分别用0.1,1.0和10.0μmol·L^(-1)氟伐他汀处理12 h;F组将miR-NC转染至0.1μmol·L^(-1)AngⅡ处理6 h后的CFs细胞中;G组将miR-590-5p转染至0.1μmol·L^(-1)AngⅡ处理6 h后的CFs细胞中;H、I、J、K组分别将anti-miR-NC、anti-miR-590-5p、pcDNA3.1和pcDNA3.1-STAT3转染至1.0μmol·L^(-1)氟伐他汀和0.1μmol·L^(-1)AngⅡ处理12 h后的CFs细胞中。用噻唑蓝法检测细胞增殖,用Transwell法检测细胞迁移和侵袭,用实时荧光定量聚合酶链反应检测miR-590-5p和信号转导和转录激活因子3(STAT3)mRNA的表达水平。结果培养48 h后,B、C、E、F、G、H、I、J、K组的细胞活性分别为0.93±0.05,0.64±0.04,0.35±0.03,0.91±0.05,0.37±0.03,0.46±0.04,0.70±0.06,0.49±0.04和0.77±0.06,迁移细胞数分别为(136.00±11.25),(105.00±9.13),(68.00±5.15),(135.00±11.25),(72.00±7.03),(85.00±6.02),(113.00±8.67),(86.00±8.40)和(106.00±8.82)个,侵袭细胞数分别为(118.00±10.11),(85.00±5.67),(54.00±4.16),(118.00±10.11),(61.00±5.31),(68.00±5.16),(98.00±7.35),(73.00±5.26)和(89.00±6.11)个,STAT3 mRNA相对表达量分别为0.65±0.04,0.54±0.03,0.28±0.02,0.64±0.06,0.12±0.01,0.35±0.03,0.50±0.04,0.32±0.03和0.55±0.05;B、C、E、F、G、H、I组的miR-590-5p相对表达量分别为0.22±0.02,0.30±0.03,0.48±0.02,0.23±0.02,0.68±0.06,0.44±0.04和0.32±0.03。C、E组的上述指标与B组相比,G组的上述指标与F组相比,I组的上述指标与H组相比,K组的上述指标与J组相比,差异均有统计学意义(均P<0.05)。结论氟伐他汀可抑制AngⅡ诱导的心肌成纤维细胞增殖、迁移和侵袭,其机制与miR-590-5p/STAT3的表达有关。Objective To investigate the effects of fluvastatin on the proliferation, migration and invasion of cardiac fibroblasts(CFs) induced by angiotensin Ⅱ(AngⅡ) and its mechanism. Methods CFs were randomly divided into A, B, C, D, E, F, G, H, I, J and K groups. A group: no fluvastatin and AngⅡ treatment;B group: stimulate cells with 0. 1 μmol·L^(-1) AngⅡ for 6 h;C,D,E groups: after 0. 1 μmol·L^(-1) AngⅡ stimulation 6 h,the cells were treated with 0. 1,1. 0 and 10. 0 μmol·L^(-1) fluvastatin for 12 h;F group: miR-NC was transfected into CFs cells treated with0. 1 μmol·L^(-1) AngⅡ for 6 h;G group: miR-590-5 p was transfected into CFs cells treated with 0. 1 μmol·L^(-1) AngⅡ for 6 h;H,I,J,K groups: anti-miR-NC,anti-miR-590-5 p,pcDNA3. 1,pcDNA3. 1-STAT3 was transfected into CFs cells treated with 1 μmol · L^(-1) fluvastatin and 0. 1 μmol · L^(-1) Ang Ⅱ for 12 h,respectively.Thiazole blue method was used to detect cell proliferation in each group. Transwell was used to detect cell migration and invasion in each group. The expression of miR-590-5 p and signal transducers and activators of transcription 3( STAT3) mRNA were determined by reverse transcription-polymerase chain reaction. Results After 48 hours of culture,the cell viabilities of B,C,E,F,G,H,I,J,and K groups were 0. 93 ± 0. 05,0. 64 ± 0. 04,0. 35 ± 0. 03,0. 91 ± 0. 05,0. 37 ± 0. 03,0. 46 ± 0. 04,0. 70 ± 0. 06,0. 49 ± 0. 04 and 0. 77 ± 0. 06;the number of migrating cells was( 136. 00 ± 11. 25),( 105. 00 ± 9. 13),( 68. 00 ± 5. 15),( 135. 00 ± 11. 25),( 72. 00 ± 7. 03),( 85. 00 ±6. 02),( 113. 00 ± 8. 67),( 86. 00 ± 8. 40) and( 106. 00 ± 8. 82);the number of invaded cells was( 118. 00 ±10. 11),( 85. 00 ± 5. 67),( 54. 00 ± 4. 16),( 118. 00 ±10. 11),( 61. 00 ± 5. 31),( 68. 00 ± 5. 16),( 98. 00 ±7. 35),( 73. 00 ±5. 26) and( 89. 00 ± 6. 11),the expression levels of STAT3 mRNA were 0. 65 ± 0. 04,0. 54 ± 0. 03,0. 28 ± 0. 02,0. 64 ± 0. 06,0. 12 ± 0. 01,0. 35 ± 0. 03,0. 50 ± 0. 04,0. 32 ± 0. 03 and 0. 55 ± 0. 0

关 键 词：氟伐他汀 微小RNA-590-5p 信号转导和转录激活因子3 血管紧张素Ⅱ 心肌纤维化 

分 类 号：R972[医药卫生—药品]