Zhang Mei, Xu Meimei
Department of Obstetrics and Gynecology, Liaocheng People's Hospital, No. 67 of Dongchang West Road, Liaocheng, 252000, China.
Fundam Clin Pharmacol. 2017 Oct;31(5):526-533. doi: 10.1111/fcp.12294. Epub 2017 May 24.
Matrix metalloproteinase (MMP)-2 and matrix metalloproteinase-9 are involved in many illnesses affecting pregnant women, including intrahepatic cholestasis of pregnancy (ICP), a serious liver abnormality during pregnancy. Epigallocatechin-3-gallate (EGCG) has been widely reported to inhibit activities of MMP-2 and MMP-9. We aimed to investigate the role of EGCG in ameliorating ICP symptoms in a rat model. Using 17α-ethinylestradiol to induce ICP in pregnant rats, we investigated the efficacy of EGCG administration on ICP symptoms, including bile flow rate, total bile acids (TBA) and MMP-2 and MMP-9 activities. Correlation study was conducted among levels of the two MMPs with other ICP symptoms. In ICP rats, activities of both MMP-2 and MMP-9 were significantly elevated. EGCG administration could inhibit the upregulation of MMP-2 and MMP-9 post-transcriptionally. Furthermore, EGCG ameliorated ICP symptoms, as evidenced by restored bile flow rate and TBA, showing efficient treatment outcomes. At last, levels of TBA and the two MMPs were found to be strongly correlated. Our study demonstrates that, for the first time, the efficacy of EGCG in ameliorating ICP symptoms by inhibiting both MMP-2 and MMP-9, which supports its potential as a novel drug in ameliorating ICP.
基质金属蛋白酶(MMP)-2和基质金属蛋白酶-9与许多影响孕妇的疾病有关,包括妊娠期肝内胆汁淤积症(ICP),这是一种妊娠期严重的肝脏异常疾病。表没食子儿茶素-3-没食子酸酯(EGCG)已被广泛报道可抑制MMP-2和MMP-9的活性。我们旨在研究EGCG在改善大鼠模型中ICP症状方面的作用。使用17α-乙炔雌二醇诱导孕鼠发生ICP,我们研究了给予EGCG对ICP症状的疗效,包括胆汁流速、总胆汁酸(TBA)以及MMP-2和MMP-9的活性。对两种MMPs的水平与其他ICP症状进行相关性研究。在ICP大鼠中,MMP-2和MMP-9的活性均显著升高。给予EGCG可在转录后抑制MMP-2和MMP-9的上调。此外,EGCG改善了ICP症状,胆汁流速和TBA的恢复证明了这一点,显示出有效的治疗效果。最后,发现TBA水平与两种MMPs密切相关。我们的研究首次证明了EGCG通过抑制MMP-2和MMP-9来改善ICP症状的疗效,这支持了其作为改善ICP的新型药物的潜力。