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熊果酸通过 AGEs-RAGE 信号通路对妊娠期糖尿病大鼠胎儿发育的治疗作用。

Therapeutic effect of ursolic acid on fetal development in pregnant rats with gestational diabetes mellitus via AGEs-RAGE signaling pathway.

机构信息

Department of Obstetrics and Gynecology, Tongde Hospital of Zhejiang Province, Hangzhou, China.

Department of Obstetrics and Gynecology, Suzhou Wuzhong People's Hospital, Suzhou, China.

出版信息

J Food Biochem. 2021 Apr;45(4):e13651. doi: 10.1111/jfbc.13651. Epub 2021 Feb 15.

Abstract

To investigate the effect of ursolic acid on the fetal development of gestational diabetes mellitus (GDM) caused by streptozotocin (STZ) and explore the potential mechanism for it. For the current experimental research, SD rats (pregnant animal) were used. STZ has been used to cause the diabetes mellitus in pregnant rats. Rats with evolved GDM were randomly divided and ursolic acid was given to pregnant rats in the experimental period up to 19 days in a dose-dependent manner. Blood samples and fetal rats of all group rats were collected at 19 days (pregnant rats), fetal rats and placental rats were weighted and the blood glucose, plasma insulin, C-peptide, and lipid parameters of pregnant women were estimated prior to delivery. Advanced serum glycation end-products (AGEs) were estimated at regular intervals in the heart and brain of pregnant rats. Monocyte Chemoattractant Protein-1 (MCP-1), NADPH oxidase 2 (Nox2), Role of advanced glycation end product (RAGE), Vascular endothelial growth factor (VEGF), p65, and vascular cell adhesion molecule 1 (VCAM-1) mRNA expression were estimated in the placenta. STZ-induced GDM pregnant rats showed significantly decreased placental weight and weight of fetal rats and dose-dependent ursolic acid treatment (p < .001) improved placental weight and weight of fetal rats at dose-dependent levels. After the ursolic acid treatment, serum blood glucose and lipid level were improved especially fasting blood glucose (FBG), high density lipoprotein (HDL), hepatic glycogen, fasting insulin (FINS), and serum insulin level and reached near to the normal control group rats. The antioxidant level of pancreas and liver were significantly (p < .001) reduced by the dose-dependent treatment of ursolic acid. Treatment with Ursolic acid moderately but not significantly decreases the risk of fetal development defects relative to the GDM group. The potential effect on fetal development in Pregnant Rats with Gestational Diabetes Mellitus via AGEs-RAGE signaling pathway was shown by Ursolic acid. PRACTICAL APPLICATIONS: As we know that the gestational diabetes mellitus increases worldwide day by day. In the current experimental study, we try to examine the gestational diabetic effect of ursolic acid. The finding of the current study showed the gestational diabetic protective effect in the female rats via AGEs-RAGE signaling pathway. The result showed the antioxidant, anti-inflammatory, and biochemical parameters. On the basis of the result, we can say that the ursolic acid can be the protective drug for treatment of gestational diabetes mellitus.

摘要

为了研究熊果酸对链脲佐菌素(STZ)引起的妊娠糖尿病(GDM)胎儿发育的影响,并探讨其潜在机制。本实验采用 SD 大鼠(妊娠动物)。STZ 已被用于诱导妊娠大鼠糖尿病。将患有 GDM 的大鼠随机分组,并在实验期间以剂量依赖性的方式给怀孕大鼠熊果酸。所有组大鼠在 19 天(怀孕大鼠)时收集血液样本和胎鼠,称重胎鼠和胎盘大鼠,并在分娩前估计孕妇的血糖、血浆胰岛素、C 肽和血脂参数。定期评估妊娠大鼠心脏和大脑中晚期糖基化终产物(AGEs)的含量。估计胎盘内单核细胞趋化蛋白-1(MCP-1)、NADPH 氧化酶 2(Nox2)、晚期糖基化终产物(RAGE)、血管内皮生长因子(VEGF)、p65 和血管细胞粘附分子 1(VCAM-1)的 mRNA 表达。STZ 诱导的 GDM 妊娠大鼠胎盘重量和胎鼠体重明显下降,熊果酸呈剂量依赖性治疗(p < 0.001)改善胎盘重量和胎鼠体重呈剂量依赖性。熊果酸治疗后,血清血糖和血脂水平改善,尤其是空腹血糖(FBG)、高密度脂蛋白(HDL)、肝糖原、空腹胰岛素(FINS)和血清胰岛素水平,接近正常对照组大鼠。熊果酸呈剂量依赖性治疗显著降低(p < 0.001)胰腺和肝脏的抗氧化水平。与 GDM 组相比,熊果酸治疗对胎儿发育缺陷的风险适度但无显著降低。熊果酸通过 AGEs-RAGE 信号通路对妊娠糖尿病大鼠胎儿发育的潜在影响。实际应用:正如我们所知,妊娠糖尿病在全球范围内日益增加。在本实验研究中,我们试图研究熊果酸对妊娠糖尿病的影响。本研究结果显示,熊果酸通过 AGEs-RAGE 信号通路对雌性大鼠具有妊娠糖尿病保护作用。结果显示了抗氧化、抗炎和生化参数。基于这一结果,我们可以说熊果酸可以作为治疗妊娠糖尿病的保护药物。

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