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蜜瓜苷 IIIE 通过激活 AMPK 信号通路减轻小鼠妊娠期糖尿病。

Mogroside IIIE attenuates gestational diabetes mellitus through activating of AMPK signaling pathway in mice.

机构信息

Heze Municipal Hospital, No. 2888, Caozhou Road, Mudan District, Heze City 274000, Shandong Province, China.

Heze Municipal Hospital, No. 2888, Caozhou Road, Mudan District, Heze City 274000, Shandong Province, China.

出版信息

J Pharmacol Sci. 2018 Nov;138(3):161-166. doi: 10.1016/j.jphs.2018.09.008. Epub 2018 Sep 26.

DOI:10.1016/j.jphs.2018.09.008
PMID:30316692
Abstract

As one kind of complications of pregnancy, gestational diabetes mellitus (GDM) can influence the health of maternal-child in clinical practice. The C57 BL/KsJ(db/+) mice, genetic GDM model, and C57 BL/KsJ (wild-type) mice were purchased and classified into three groups: normal pregnancy (C57 BL/KsJ), GDM (C57 BL/KsJ), and GDM plus Mogroside IIIE (20.0 mg/kg) group. GDM symptoms (maternal body weight, serum glucose, and insulin levels), glucose and insulin tolerance, and reproductive outcome (body weight at birth and litter size of offspring) were investigated. The inflammatory factors such as IL-1β, IL-6, and TNF-α in the serum and the pancreas were detected by ELISA and qRT-PCR, while the expression of pAMPK, AMPK, pHDAC4, HDAC4, and G6Pase in the livers were analyzed by Western Blot. Mogroside IIIE greatly improved glucose metabolism, insulin tolerance, and reproductive outcome of the GDM mice. Moreover, Mogroside IIIE treatment significantly decreased inflammatory factors expression and relieved GDM symptoms through enhanced AMPK activation, inhibited HDAC4 expression, and reduced production of G6Pase. The alleviation of GDM by Mogroside IIIE was mediated by elevated AMPK activation, which in turn inhibited HDAC4 phosphorylation, and eventually down-regulated G6Pase expression and activity.

摘要

作为妊娠的一种并发症,妊娠期糖尿病(GDM)会影响母婴的健康,这在临床上已经得到证实。本研究选用 C57 BL/KsJ(db/+) 小鼠,即遗传 GDM 模型,以及 C57 BL/KsJ(野生型)小鼠作为研究对象,将其分为三组:正常妊娠组(C57 BL/KsJ)、GDM 组(C57 BL/KsJ)和 GDM 加三萜总皂苷组(20.0mg/kg)。我们对 GDM 症状(母体体重、血清葡萄糖和胰岛素水平)、葡萄糖和胰岛素耐量以及生殖结局(出生时体重和后代窝仔数)进行了研究。通过 ELISA 和 qRT-PCR 检测血清和胰腺中的炎症因子(如 IL-1β、IL-6 和 TNF-α),通过 Western Blot 分析肝脏中 pAMPK、AMPK、pHDAC4、HDAC4 和 G6Pase 的表达。三萜总皂苷显著改善了 GDM 小鼠的葡萄糖代谢、胰岛素耐量和生殖结局。此外,三萜总皂苷通过增强 AMPK 激活、抑制 HDAC4 表达和减少 G6Pase 的产生,显著降低了炎症因子的表达,缓解了 GDM 症状。三萜总皂苷通过升高 AMPK 激活来缓解 GDM,进而抑制 HDAC4 磷酸化,最终下调 G6Pase 的表达和活性。

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