银纳米颗粒调节链脲佐菌素诱导的糖尿病大鼠肾脏中的S/JAK/STAT和P13K/Akt/PTEN信号通路。

silver nanoparticles modulate S/JAK/STAT and P13K/Akt/PTEN signalling pathways in the kidney of streptozotocin-induced diabetic rats.

作者信息

Elekofehinti Olusola Olalekan, Oyedokun Victor Oluwatoyin, Iwaloye Opeyemi, Lawal Akeem Olalekan, Ejelonu Oluwamodupe Cecilia

机构信息

Bioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology Akure, Akure, Ondo State Nigeria.

Biochemistry Programme, Department of Chemical Sciences, School of Sciences, Olusegun Agagu University of Science and Technology, Okitipupa, Ondo State Nigeria.

出版信息

J Diabetes Metab Disord. 2021 Feb 5;20(1):245-260. doi: 10.1007/s40200-021-00739-w. eCollection 2021 Jun.

DOI:10.1007/s40200-021-00739-w

PMID:34178835

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8212297/

Abstract

OBJECTIVES

Diabetes nephropathy (DN) is one of the complications of diabetes mellitus (DM) marked by gradual progressive loss of renal function. SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways are among the chain of interactions implicated in the onset, progression and pathology of DN. (bitter melon) is often used in folk medicine as therapy for DM due to its hypoglycemic properties. This study was designed to evaluate silver nanoparticles' therapeutic effect on DN-induced by streptozotocin (STZ) in Wistar rats.

METHODS

The nanoparticles used was synthesized using the filtrate from the plant methanolic extract added to 1 mM concentration of aqueous silver nitrate. DM was induced in Wistar rats by intraperitoneal injection of STZ (65 mg/kg). The animals' treatment groups were divided into; Diabetic control (65 mg/kg STZ), Control, and groups treated with silver nitrate (10 mg/kg), nanoparticles (50 mg/kg), metformin (100 mg/kg), and plant extract (100 mg/kg). Treatment was terminated after 11 days. RT-PCR determined renal mRNA expression of Akt, PI3k, PTEN, TGF-β, JAK2, STAT3, STAT5, SOCS3, SOCS4 and glucokinase (GCK). Consequently, characterized compounds from identified from literatures were docked with PI3K, JAK2 and TGF-β and STAT3 to retrieve potential hits.

RESULTS

Oral administration of nanoparticles (50 mg/kg) to STZ-induced diabetic untreated rats significantly (( 0.05) down-regulated the mRNA expression of Akt, PI3k, TGF-β, JAK2, STAT3 and upregulated the mRNA expression of PTEN, SOCS3 and SOCS4, thus establishing the role of nanoparticles in alleviating DN in diabetic rats. Additionally, there was a significant up-regulation of glucose metabolizing gene (glucokinase) upon administering nanoparticles. Molecular docking results showed 12 compounds from bitter melon with docking score ranging from -6.114 kcal/mol to -8.221 kcal/mol that are likely to exert anti-diabetic properties.

CONCLUSION

Observation drawn from this study suggests that nanoparticles ameliorate DN through regulation of SOCS/JAK/STAT and PI3K/Akt/PTEN signalling pathways.

摘要

目的

糖尿病肾病（DN）是糖尿病（DM）的并发症之一，其特征是肾功能逐渐进行性丧失。SOCS/JAK/STAT和PI3K/Akt/PTEN信号通路参与了DN的发生、发展和病理过程。苦瓜因其降血糖特性，在民间医学中常被用作治疗DM的药物。本研究旨在评估银纳米颗粒对链脲佐菌素（STZ）诱导的Wistar大鼠糖尿病肾病的治疗效果。

方法

所用纳米颗粒是通过将植物甲醇提取物的滤液加入1 mM浓度的硝酸银水溶液中合成的。通过腹腔注射STZ（65 mg/kg）诱导Wistar大鼠患糖尿病。动物治疗组分为：糖尿病对照组（65 mg/kg STZ）、对照组，以及用硝酸银（10 mg/kg）、纳米颗粒（50 mg/kg）、二甲双胍（100 mg/kg）和植物提取物（100 mg/kg）治疗的组。11天后终止治疗。RT-PCR测定肾组织中Akt、PI3k、PTEN、TGF-β、JAK2、STAT3、STAT5、SOCS3、SOCS4和葡萄糖激酶（GCK）的mRNA表达。因此，将文献中鉴定出的特征化合物与PI3K、JAK2、TGF-β和STAT3进行对接，以寻找潜在的活性成分。

结果

对STZ诱导的未经治疗的糖尿病大鼠口服纳米颗粒（50 mg/kg）显著（P<0.05）下调了Akt、PI3k、TGF-β、JAK2、STAT3的mRNA表达，并上调了PTEN、SOCS3和SOCS4的mRNA表达，从而确定了纳米颗粒在减轻糖尿病大鼠DN中的作用。此外，给予纳米颗粒后，葡萄糖代谢基因（葡萄糖激酶）显著上调。分子对接结果显示，苦瓜中的12种化合物对接分数在-6.114 kcal/mol至-8.221 kcal/mol之间，可能具有抗糖尿病特性。