小檗碱对大鼠高血压左室肥厚心肌表达miRNA-29b的影响及抑制心肌纤维化的作用机制

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摘要目的探讨小檗碱（BBR）对大鼠高血压左室肥厚心肌表达miRNA-29b的影响及抑制心肌纤维化的作用机制。方法将25只雄性SD大鼠随机分成假手术组（Sham组，n = 7），模型组（Model组，n = 9）和模型给药组（Model+BBR组，n = 9）。腹主动脉缩窄法制备大鼠高血压心肌肥厚模型，术后8周测定各组超声心动图、心脏肥大指数，Masson染色检测心肌组织纤维化，RT-PCR检测心肌组织miRNA-29b及其靶基因col1α1和col3α1 mRNA表达。结果 Model组的舒张末期室间隔厚度（IVSd）、舒张末期左室后壁厚度（LVPWd）均厚于Sham组，左室长轴缩短分数（FS）、射血分数（EF）均低于Sham组，差异有统计学意义（P < 0.05）；Model+BBR组的IVSd、LVPWd均薄于Model组，FS、EF均高于Model组，差异有统计学意义（P < 0.05）。Model组的心脏重量显著重于Sham组，心脏/体重比显著高于Sham组（P < 0.01）；Model+BBR组的心脏重量轻于Model组，心脏/体重比低于Model组（P < 0.05）。Model组的心肌胶原蛋白体积分数显著高于Sham组（P < 0.01）；Model+BBR组的心肌胶原蛋白体积分数低于Model组（P < 0.05）。Model组的Col1α1 mRNA和Col3α1 mRNA水平均高于Sham组，miRNA-29b水平低于Sham组（P ＜ 0.05或P < 0.01）；Model+BBR组的Col1α1 mRNA和Col3α1 mRNA水平均低于Model组，miRNA-29b水平高于Model组（P ＜ 0.05）。结论 BBR可能通过下调miRNA-29b水平及上调其靶基因表达水平，抑制高血压心肌肥厚模型心肌肥厚和心肌纤维化。

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	郑颖李小华李强张忆雪陈漠水

关键词 ：小檗碱, 心肌肥厚, 心肌纤维化, miRNA-29b

Abstract：Objective To investigate the effect of Berberine on expression of miRNA-29b in hypertensive left ventricular hypertrophy myocardial tissue and the mechanism of inhibition for myocardial fibrosis. Methods Male SD rats (n = 25) were randomly divided into sham operation group (sham group, n = 7), model group (model group, n = 9) and model administration group (model+BBR group, n = 9). Rat model of hypertensive cardiac hypertrophy was established by abdominal aortic coarctation. The cardiac structure and function were measured by echocardiography. The cardiac hypertrophy index was measured at 8 weeks postoperatively. The changes of myocardial fibrosis were detected by Masson staining. The expression of miRNA-29b and its target genes col1α1 and col3α1 mRNA in myocardial tissue were detected by RT-PCR. Results IVSd and LVPWd in model group were thicker than those in sham group, and FS and EF were lower than those in Sham group (P < 0.05). IVSd and LVPWd of model+BBR group were thinner than those of model group, and FS and EF were higher than those of model group (P < 0.05). Heart weight of model group was significantly heavier than that of sham group, and heart/body weight ratio was significantly higher than that of sham group (P < 0.01). Heart weight of model+BBR group was lighter than that of model group, and the heart/body weight ratio was lower than that of model group (P < 0.05). The volume fraction of myocardial collagen in model group was significantly higher than that in sham group (P < 0.01). The volume fraction of myocardial collagen in model+BBR group was lower than that in model group (P < 0.05). The level of col1α1 mRNA and col3α1 mRNA in model group was higher than those in sham group, and the level of miRNA-29b was lower than that in sham group (P < 0.05 or P < 0.01). The level of col1α1 mRNA and col3α1 mRNA in model+BBR group was lower than those in model group, and the level of miRNA-29b was higher than that in model group (P < 0.05). Conclusion Berberine inhibits myocardial hypertrophy and myocardial fibrosis by down-regulating miRNA-29b levels and up-regulating its target gene expression.

Key words： Berberine Cardiac hypertrophy Cardiac fibrosis miRNA-29b

基金资助:海南省自然科学基金项目（20158339）。

通讯作者: 李小华（1971.9-），女，主任医师，主要从事高血压病、冠心病的基础及临床研究。

作者简介: 郑颖（1977.9-），女，硕士，副主任医师，主要从事高血压病、心律失常、冠心病的基础及临床研究。

引用本文:

郑颖李小华李强张忆雪陈漠水. 小檗碱对大鼠高血压左室肥厚心肌表达miRNA-29b的影响及抑制心肌纤维化的作用机制[J]. 中国医药导报, 2020, 17(14): 19-22.
ZHENG Ying LI Xiaohua LI Qiang ZHANG Yixue CHEN Moshui. Effect of Berberine on the expression of miRNA-29b in left ventricular hypertrophy and the mechanism of inhibition of myocardial fibrosis. 中国医药导报, 2020, 17(14): 19-22.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2020/V17/I14/19

[1] 张慧阁，郑荣果，任红欣.阿托伐他汀逆转原发性高血压患者左心室心肌肥厚临床研究[J].中国药业，2018，27（24）：71-73.
[2] Werfel S，Leierseder S，Ruprecht B，et al. Preferential microRNA targeting revealed by in vivo competitive binding and differential Argonaute immunoprecipitation [J]. Nucleic Acids Res，2017，45（17）：10218-10228.
[3] Liao Y，Chen K，Dong X，et al. Berberine inhibits cardiac remodeling of heart failure after myocardial infarction by reducing myocardial cell apoptosis in rats [J]. Exp Ther Med，2018，16（3）：2499-2505.
[4] Ckv N，Macedo CT，Brr C，et al. Circulating miRNAs as potential biomarkers associated with cardiac remodeling and fibrosis in chagas disease cardiomyopathy [J]. Int J Mol Sci，2019，20（16）：E4064.
[5] 刘静，崔海峰，李思耐，等.压力负荷诱导的大鼠舒张性心力衰竭模型的改良及效果探讨[J].医学研究杂志，2017，46（1）：34-38，52.
[6] 刘成芳，刘继斌，王瑾，等.心肌内向整流钾电流激动剂扎考比利对腹主动脉缩窄大鼠心功能和心肌纤维化的作用[J].中国循环杂志，2019，34（6）：606-611.
[7] 梁悦，张光涛，汤晓萌，等.压力超负荷致心肌肥厚形成过程中收缩压和心重指数的变化[J].中国医药导报，2017， 14（14）：16-19.
[8] Travers JG，Kamal FA，Robbins J，et al. Cardiac fibrosis：the fibroblast awakens [J]. Circ Res，2016，118（6）：1021-1040.
[9] Kong P，Christia P，Frangogiannis NG. The pathogenesis of cardiac fibrosis [J]. Cell Mol Life Sci，2014，71（4）：549-574.
[10] 唐青，邢晓为，黄利华，等.miRNA在高血压疾病中的应用及调控机制[J].中华高血压杂志，2013，21（2）：121-126.
[11] Moghaddam AS，Afshari JT，Esmaeili SA，et al. Cardioprotective microRNAs：lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease [J]. Atherosclerosis，2019，285：1-9.
[12] 张国华.TGF-β1/Smads信号通路在高血压心肌纤维化中的调控机制研究进展[J].山东医药，2014，54（7）：85-87.
[13] Syed M，Ball JP，Mathis KW，et al. MicroRNA-21 ablation exacerbates aldosterone-mediated cardiac injury，remodeling，and dysfunction [J]. Am J Physiol Endocrinol Metab，2018，315（6）：E1154-E1167.
[14] 朱珂，娄利霞，高永红，等.扶正化瘀方对血管紧张素Ⅱ诱导的心肌成纤维细胞miR-29b-5p表达的影响[J].医学综述，2019，25（13）：2689-2694.
[15] Liu Y，Wang H，Wang X，et al. MiR-29b inhibits ventricular remodeling by activating notch signaling pathway in the rat myocardial infarction model [J]. Heart Surg Forum，2019，22（1）：E19-E23.
[16] 于怡卉，李明慧，张瑶俊，等.小檗碱对压力负荷所致心肌肥厚大鼠的保护作用[J].南京医科大学学报:自然科学版，2015，35（1）：40-45.
[17] 王小英，林佳，潘竞锵.小檗碱及同系物抑制心肌肥厚和心室重构的药理作用[J].今日药学，2012，22（1）： 46-50.
[18] 王英伟，李秀东，孙明君，等.小檗碱对力竭运动诱导的大鼠心肌损伤具有保护作用[J].中华心血管病杂志，2019， 47（8）：647-652.
[19] Dong S，Zhang S，Chen Z，et al. Berberine could ameliorate cardiac dysfunction via interfering myocardial lipidomic profiles in the rat model of diabetic cardiomyopathy [J]. Front Physiol，2018，9：1042.
[20] Zhu ML，Yin YL，Ping S，et al. Berberine promotes ischemia-induced angiogenesis in mice heart via upregulation of microRNA-29b [J]. Clin Exp Hypertens，2017，39（7）：672-679.