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通过靶向 PPARγ 调控的基因表达抑制 2 型糖尿病的发展。

Inhibition of Type-2 Diabetes Mellitus Development by Sophocarpine through Targeting PPARy-Regulated Gene Expression.

机构信息

Health Management Center, Ningxia Medical University General Hospital, Yinchuan, Ningxia, China.

Department of Endocrinology and Metabolism, Aerospace Center Hospital, Beijing, China.

出版信息

Dokl Biochem Biophys. 2021 Mar;497(1):137-143. doi: 10.1134/S1607672921020150. Epub 2021 Apr 24.

Abstract

Diabetes mellitus (DM), a metabolic disorder, is the causes of oxidative stress leading to complications in micro- and macro-vascular system. The present study investigated sophocarpine for anti-diabetic potential in vivo in mice model. Sophocarpine administration to diabetic mice significantly (p < 0.05) attenuated glucose content in the plasma. The diabetes mediated lowering of GSH, ceruloplasmin and vitamin E was prevented in mice plasma by sophocarpine administration. Sophocarpine significantly (p < 0.05) reversed diabetes mediated suppression of insulin level and total Hb content in the mice plasma. In sophocarpine administrated diabetic mice C-peptide level was elevated and glycosylated hemoglobin content was suppressed significantly (p < 0.05) relative to diabetic group. Administration of sophocarpine significantly (p < 0.05) repressed diabetes mediated increase in TG and TC levels in dose-based manner. Administration of sophocarpine exhibited preventive role against diabetes mediated pathological damage to pancreas in the mice. Sophocarpine administration to diabetic mice repressed PPARγ recruitment significantly (p < 0.05) in dose-dependent manner. Sophocarpine prevents oxidative stress mediated pancreatic damage through increase in vitamin E, GSH and C-peptide levels, Moreover, the PPARγ activity was down-regulated, LDL-c content lowered and HDL-c level elevated in diabetic mice by sophocarpine. Therefore, sophocarpine may be developed for treatment of diabetes, however, further in vivo studies need to confirm the same.

摘要

糖尿病(DM)是一种代谢紊乱,可导致氧化应激,从而引发微血管和大血管系统的并发症。本研究在糖尿病小鼠模型中研究了苦参碱的抗糖尿病潜力。苦参碱给药可显著(p < 0.05)降低糖尿病小鼠血浆中的葡萄糖含量。糖尿病导致的血浆 GSH、铜蓝蛋白和维生素 E 降低,可通过苦参碱给药得到预防。苦参碱可显著(p < 0.05)逆转糖尿病介导的对血浆胰岛素水平和总 Hb 含量的抑制。在苦参碱给药的糖尿病小鼠中,C-肽水平升高,糖化血红蛋白含量显著(p < 0.05)降低,与糖尿病组相比。苦参碱给药可显著(p < 0.05)以剂量依赖的方式抑制糖尿病介导的 TG 和 TC 水平升高。苦参碱给药对糖尿病介导的小鼠胰腺病理损伤具有预防作用。苦参碱给药可显著(p < 0.05)抑制糖尿病小鼠中 PPARγ 的募集,呈剂量依赖性。苦参碱通过增加维生素 E、GSH 和 C-肽水平来防止氧化应激介导的胰腺损伤,此外,PPARγ 活性降低,LDL-c 含量降低,HDL-c 水平升高在糖尿病小鼠中由苦参碱。因此,苦参碱可能被开发用于治疗糖尿病,但需要进一步的体内研究来证实这一点。

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