Pharmacokinetic, antihypertension and deep sequencing MiRNomes analysis of aorta from SHR fed with EGCG

Mechanism (s) of the epigallocatechin-3-gallate (EGCG) as major effective components in green tea regarding the reduction of hypertensive risk might associate with microRNAs (miRNAs). The plasma distribution of EGCG and epigallocatechin (EGC) in Sprague-Dawley rats were analyzed pharmacokinetically and found that they did not distribute well in plasma but widely in tissues, and their plasma deposition best fitted a mono-compartmental model with Cmax (6.65 vs 4.45 μg/mL) and Tmax (15 vs 10 min). Blood pressure monitoring of spontaneously hypertensive rats (SHR) intragastrically administrated with 300 mg/kg BW showed that systolic blood pressure (SBP) decreased to the lowest point by 34.04 mmHg and recovered by 23.39 mmHg after 15 and 30 min of administration, respectively, and it decreased again at 60 min and recovered at time 2 h. Total 150 upregulated and 18 downregulated miRNAs were identified via the deep sequencing and were 1.0 or 0.5 fold to the control group (P<0.01) after EGCG administration. And, hypertension-associated miRNA-126-3p and miRNA-150 were further validated by qRT-PCR. It might help explore novel pathways involving antihypertensive effect of EGCG.绿茶主要有效成分表没食子儿茶素没食子酸酯（epigallocatechin-3-gallate, EGCG）降低高血压风险的作用机制，可能与微小RNA（microRNAs, miRNAs）相关。本研究对斯普拉格-道利大鼠（Sprague-Dawley rats）体内EGCG与表没食子儿茶素（epigallocatechin, EGC）的血浆分布进行了药代动力学分析，结果显示二者在血浆中分布水平较低，但广泛分布于各组织中；其血浆药物浓度-时间过程最符合单房室模型，峰浓度（Cmax）分别为6.65 μg/mL与4.45 μg/mL，达峰时间（Tmax）分别为15 min与10 min。对灌胃给予300 mg/kg体重剂量的自发性高血压大鼠（spontaneously hypertensive rats, SHR）进行血压监测发现：给药后15 min时，其收缩压（systolic blood pressure, SBP）降至最低值，较基线降低34.04 mmHg；给药后30 min时，收缩压回升23.39 mmHg；随后在60 min时收缩压再次下降，并于2小时时恢复至初始水平。经深度测序共鉴定得到150个上调微小RNA及18个下调微小RNA，EGCG给药后，这些微小RNA的表达量较对照组分别为1.0倍或0.5倍（P<0.01）。此外，研究通过实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）进一步验证了与高血压相关的miRNA-126-3p与miRNA-150的表达变化。本研究可为探索EGCG降压作用的全新通路提供有益参考。