miRNA-195、贝那普利与自发性高血压大鼠主动脉重构

miRNA-195,Benazepril and Aortic Remodeling in Spontaneously Hypertensive Rats

目的观察自发性高血压大鼠(SHR)的主动脉形态结构及其表达miRNA-195水平的变化,以及贝那普利干预对其影响。方法 8周龄雄性SHR及Wistar大鼠,随机分为SHR对照组、SHR贝那普利组(SHR干预组)、Wistar对照组、Wistar贝那普利组(Wistar干预组),SHR干预组和Wistar干预组大鼠予贝那普利10 mg/(kg·d)干预,8周后,测定各组大鼠尾动脉血压,HE染色检测大鼠主动脉结构形态,实时荧光定量PCR检测大鼠主动脉miRNA-195表达,Western blot检测大鼠主动脉转化生长因子β1(TGF-β1)、Smad3蛋白、Ⅰ型胶原(COL-Ⅰ)和Ⅲ型胶原(COL-Ⅲ)蛋白表达水平。结果贝那普利干预8周后,SHR干预组大鼠尾动脉收缩压及舒张压均显著低于SHR对照组(P<0.01),高于Wistar对照组(P<0.01)。SHR干预组大鼠主动脉miRNA-195表达高于SHR对照组、Wistar干预组及Wistar对照组(P<0.05或P<0.01);SHR干预组大鼠主动脉TGF-β1和Smad3蛋白表达低于SHR对照组(P<0.05),但高于Wistar干预组(P<0.01);SHR干预组大鼠主动脉COL-Ⅰ和COL-Ⅲ表达低于SHR对照组(P<0.05或P<0.01),但高于Wistar干预组(P<0.01);SHR干预组大鼠主动脉内中膜结构较SHR对照组改善,但未能恢复到Wistar对照组水平。结论贝那普利干预可改善SHR主动脉重构,这一作用可能与miRNA-195抑制TGF-β1/Smad3信号通路有关。

Aim To explore the changes of aortic morphology and expression of miRNA-195 in aorta of spontane- ously hypertensive rats （SHR）, and the effect of benazepril on them. Methods 8-week-old male SHRs were random- ly divided into SHR benazepril treatment group （SB group, benazepril 10 mg/（ kg · d）, n =8 ） and SHR control group （ SC group, n = 8）, and Wistar rats of the same age served as control were also randomly divided into benazepril treatment group （ WB group, benazepril 10 mg/（kg · d）, n -=-8） and control group （WC group, n =8）. After 8 weeks treatment, tail arterial blood pressures of rats were measured, aortic morphology were detected by hemotoxylin and eosin staining, and expression level of mi RNA-195 in aorta of rats were detected by qRT-PCR, and expression level of TGF-131, Smad3, COL- Ⅰ and COL-Ⅲ proteins were detected by Western blot. Results After 8 weeks of medication, the tail arterial systolic blood pressure and diatolic blood pressure of rats in SB group was lower than that in SC group （P 〈 0. 01 ）, but was higher than that in WB group （ P 〈 0. 0l ）. The expression of miRNA-195 in aorta of rats in SB group was higher than that in SC group, WB group and WC group （P 〈 0. 05 or P 〈 0. 01 ）. The expression levels of TGF-131 and Smad3 in aorta of rats in SB group were lower those that in SC group （P 〈 0. 05 ）, but higher than those in WB group （ P 〈 0. O1 ）, and the ex- pression of COL- Ⅰ and COL-Ⅲ protein showed a similar change （P 〈 0.05 or P 〈 0. 01 ）. Aortic morphology of rats in SB group was improved compared with SC group, but did not reach the level of that in WC group. Conclusions Treatment with Benazepril can ameliorate the aortic morphology of SHR, and miRNA-195 may play a role in this process, by inhibiting TGF-β1/Smad3 signaling pathway.