中国中药杂志

2021, v.46(19) 5064-5071

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竹节参皂苷Ⅳa通过调节miR199a-5p/Atg5改善大鼠心肌肥厚的实验研究
Chikusetsu saponin Ⅳa ameliorates myocardial hypertrophy of rats through regulating expression of miR199a-5p/Atg5

伍学翠;袁成福;何毓敏;周志勇;罗悦;杨梦婷;李晓晓;刘朝奇;
WU Xue-cui;YUAN Cheng-fu;HE Yu-min;ZHOU Zhi-yong;LUO Yue;YANG Meng-ting;LI Xiao-xiao;LIU Chao-qi;Affiliated Renhe Hospital of China Three Gorges University;Medical College, China Three Gorges University;

摘要(Abstract):

研究竹节参皂苷Ⅳa(chikusetsu saponinⅣa, CHS-Ⅳa)对异丙肾上腺素(isoproterenol, ISO)诱导的大鼠心肌肥厚的改善作用,并探讨其可能的分子机制。采用ISO诱导大鼠心肌肥厚模型,同时采用CHSⅣa低、高剂量(5、15 mg·kg~(-1)·d~(-1))进行干预。测量大鼠尾动脉压,心脏超声检查,计算心重指数,HE染色法观察心肌组织形态学改变,Masson染色法观察心肌组织中胶原沉积情况;qRT-PCR法检测心肌组织肥大指标心钠肽(atrial natriuretic peptide, ANP)、脑钠肽(brain natriuretic peptide, BNP)、自噬相关基因5(autophagy related gene 5,Atg5)、选择性自噬接头蛋白P62/SQSTM1(P62)、自噬调控因子(beclin1)、miR199a-5p mRNA的表达情况;Western blot法检测Atg5蛋白表达情况。结果显示,模型组中大鼠尾动脉收缩压、心重指数明显升高;左室心肌厚度明显增厚;心肌细胞体积增大,心肌纤维排列紊乱,间质增宽,且有大量胶原蛋白聚集在细胞外间质和血管周围;ANP、BNP表达明显增加;自噬相关基因P62表达升高,beclin1表达降低。经过CHSⅣa不同剂量干预后,可有效改善大鼠心肌肥厚,增强心肌组织中自噬活性,miR199a-5p表达降低而Atg5表达升高,同时生物信息学预测Atg5是miR199a-5p靶基因。这些结果表明,CHSⅣa药物可能通过miR-199a-5p/Atg5信号通路调节心肌细胞自噬发挥对心肌肥厚模型的干预作用。
The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.

关键词(KeyWords): 竹节参皂苷Ⅳa;心肌肥厚;miR199a-5p;自噬;Atg5
chikusetsu saponin Ⅳa;myocardial hypertrophy;miR199a-5p;autophagy;Atg5

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基金项目(Foundation): 国家自然科学基金项目(81673675)

作者(Author): 伍学翠;袁成福;何毓敏;周志勇;罗悦;杨梦婷;李晓晓;刘朝奇;
WU Xue-cui;YUAN Cheng-fu;HE Yu-min;ZHOU Zhi-yong;LUO Yue;YANG Meng-ting;LI Xiao-xiao;LIU Chao-qi;Affiliated Renhe Hospital of China Three Gorges University;Medical College, China Three Gorges University;

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