中文摘要：

目的观察微小RNA-145（microRNA-145,miR-145）在高血压血管内膜增生中的作用。方法常规HE染色观察自发性高血压大鼠（SHR）和对照大鼠（WKY）主动脉内膜增生情况,逆转录多聚酶链反应（RT-PCR）方法检测不同病程SHR大鼠主动脉中miR-145的表达水平,并应用miR-145前体premiR-145和抑制剂2’OMe-miR-145分别升高和抑制血管平滑肌细胞（smooth muscle cell,VSMC）中miR-145的表达水平,从分化标志蛋白α平滑肌肌动蛋白（α-SMA）表达水平、VSMC的增殖和迁移能力等方面检测VSMC表型转化情况。结果①SHR大鼠主动脉内膜增生,内膜/中膜面积百分比（39.7±12.1）%显著高于WKY组（3.8±1.2）%（P=0.001）,α-SMA染色阳性的VSMC是增生内膜的主要细胞成分;②与WKY相比,SHR大鼠主动脉来源的VSMC表型转化明显增多,表现为增殖和迁移能力升高,而α-SMA表达降低（P〈0.01）;③SHR大鼠主动脉中的miR-145水平在8周龄时开始下降（P=0.045 6）,至18周龄时降至仅为WKY组的7.5%;④应用premiR-145可上调SHR-VSMC中α-SMA的表达（P=0.005 6）并促进VSMC增殖迁移过程（P〈0.01）,而2’OMe-miR-145可抑制VSMC中α-SMA的表达（P=0.023 2）和VSMC增殖迁移过程（P〈0.01）。结论高血压时动脉中miR-145水平呈进行性下降,可能是引起VSMC表型转化并促进动脉内膜增生的一个重要机制。

英文摘要：

Objective To determine the effect of miR-145 on arterial intimal hyperplasia in hypertension.Methods Spontaneous hypertension rats（SHR） and Wistar-Kyoto（WKY） rats were used in this study.Aortic intimal hyperplasia was evaluated pathologically.The expression of miR-145 in aorta of SHR was detected by reverse transcription polymerase chain reaction（RT-PCR）.The phenotypic modulation of vascular smooth muscle cells（VSMCs） was assessed by detecting the expression of α-smooth muscle actin（α-SMA） and the capability of proliferation and migration in the presence of miR-145 precursor,premiR-145,or inhibitor 2＇OMe-miR-145.Results SHR aortas exhibited obvious neo-intima formation which was composed primarily of VSMCs,with the ratios of intima/media significant higher than WKY rats（P=0.001）.SHR-derived VSMCs exhibited marked phenotypic modulation,however,the expression of α-SMA was lower（P0.01）.The expression of miR-145 in SHR aortas was declined at the 8th week（P=0.045 6） and reduced to 7.5% of that of WKY rats at the 18th week.Expression of α-SMA and proliferative and migratory capacities of VSMCs were respectively upregulated and downregulated by premiR-145 and 2＇OMe-miR-145.Conclusion The expression of miR-145 decreases progressively during hypertension,which may at least partly contribute to the excessive VSMCs phenotypic modulation and thus arterial intimal hyperplasia.