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采用代谢组学方法系统评估链脲佐菌素诱导的大鼠糖尿病代谢变化。

Systematic assessment of streptozotocin-induced diabetic metabolic alterations in rats using metabolomics.

机构信息

Department of Endocrinology, Tengzhou Central People's Hospital, Tengzhou, China.

Translational Pharmaceutical Laboratory, Jining First People's Hospital, Shandong First Medical University, Jining, China.

出版信息

Front Endocrinol (Lausanne). 2023 Jan 24;14:1107162. doi: 10.3389/fendo.2023.1107162. eCollection 2023.

Abstract

PURPOSE

Type 1 diabetes is characterized by elevated blood glucose levels, which negatively impacts multiple organs and tissues throughout the body, and its prevalence is on the rise. Prior reports primarily investigated the serum and urine specimen from diabetic patients. However, only a few studies examined the overall metabolic profile of diabetic animals or patients. The current systemic investigation will benefit the knowledge of STZ-based type 1 diabetes pathogenesis.

METHODS

Male SD rats were arbitrarily separated into control and streptozotocin (STZ)-treated diabetic rats (n = 7). The experimental rats received 50mg/kg STZ intraperitoneal injection daily for 2 consecutive days. Following 6 weeks, metabolites were assessed gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to screen for differentially expressed (DE) metabolites between the induced diabetic and normal rats.

RESULTS

We identified 18, 30, 6, 24, 34, 27, 27 and 12 DE metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of STZ-treated diabetic rats, compared to control rats. Based on our analysis, the largest differences were observed in the amino acids (AAs), B-group vitamin, and purine profiles. Using the metabolic pathway analysis, we screened 13 metabolic pathways related to the STZ-exposed diabetes pathogenesis. These pathways were primarily AA metabolism, followed by organic acids, sugars, and lipid metabolism.

CONCLUSION

Based on our GC-MS analysis, we identified potential metabolic alterations within the STZ-exposed diabetic rats, which may aid in the understanding of diabetes pathogenesis.

摘要

目的

1 型糖尿病的特征是血糖水平升高,这会对全身多个器官和组织造成负面影响,其患病率呈上升趋势。先前的报告主要研究了糖尿病患者的血清和尿液标本。然而,只有少数研究检查了糖尿病动物或患者的整体代谢特征。目前的系统研究将有助于了解基于链脲佐菌素的 1 型糖尿病发病机制。

方法

雄性 SD 大鼠被任意分为对照组和链脲佐菌素(STZ)处理的糖尿病大鼠(n = 7)。实验大鼠每天腹腔注射 50mg/kg STZ,连续 2 天。6 周后,采用气相色谱-质谱联用(GC-MS)评估代谢物,并采用多元分析筛选诱导型糖尿病大鼠与正常大鼠之间的差异表达(DE)代谢物。

结果

与对照组大鼠相比,我们在 STZ 处理的糖尿病大鼠的血清、心脏、肝脏、肾脏、皮质、肾脂、海马和棕色脂肪组织中分别鉴定出 18、30、6、24、34、27、27 和 12 个 DE 代谢物。根据我们的分析,在氨基酸(AA)、B 族维生素和嘌呤谱中观察到最大的差异。通过代谢途径分析,我们筛选出与 STZ 暴露导致糖尿病发病机制相关的 13 条代谢途径。这些途径主要是 AA 代谢,其次是有机酸、糖和脂质代谢。

结论

基于我们的 GC-MS 分析,我们确定了 STZ 暴露的糖尿病大鼠中潜在的代谢变化,这可能有助于了解糖尿病的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4284/9902650/87201bb4672f/fendo-14-1107162-g001.jpg

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