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二甲双胍和葛根芩连汤促进 STZ 诱导糖尿病大鼠胰岛 α 细胞增殖。

Metformin and Gegen Qinlian Decoction boost islet α-cell proliferation of the STZ induced diabetic rats.

机构信息

Medical experiment center, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.

Toxicology Centre, University of Saskatchewan, Saskatoon, S7N 5B3, Canada.

出版信息

BMC Complement Med Ther. 2022 Jul 20;22(1):193. doi: 10.1186/s12906-022-03674-2.

Abstract

BACKGROUND

The traditional Chinese medicine Gegen Qinlian Decoction (GQD), as well as metformin, had been reported with anti-diabetic effects in clinical practice.

OBJECTIVE

To verify whether these two medicines effectively ameliorate hyperglycemia caused by deficiency of islet β-cell mass which occurs in both type 1 and type 2 diabetes.

METHODS

SD rats were injected with a single dose of STZ (55 mg/kg) to induce β-cell destruction. The rats were then divided into control, diabetes, GQD and metformin group. GQD and metformin groups were administered with GQD extract or metformin for 6 weeks. The islet α-cell or β-cell mass changes were tested by immunohistochemical and immunofluorescent staining. The potential targets and mechanisms of GQD and metformin on cell proliferation were tested using in silico network pharmacology. Real-time PCR was performed to test the expression of islet cells related genes and targets related genes.

RESULTS

Both GQD and metformin did not significantly reduce the FBG level caused by β-cell mass reduction, but alleviated liver and pancreas histopathology. Both GQD and metformin did not change the insulin positive cell mass but increased α-cell proliferation of the diabetic rats. Gene expression analysis showed that GQD and metformin significantly increased the targets gene cyclin-dependent kinase 4 (Cdk4) and insulin receptor substrate (Irs1) level.

CONCLUSION

This research indicates that GQD and metformin significantly increased the α-cell proliferation of β-cell deficiency induced diabetic rats by restoring Cdk4 and Irs1 gene expression.

摘要

背景

中药葛根芩连汤(GQD)和二甲双胍在临床上均有降血糖作用。

目的

验证这两种药物是否能有效改善 1 型和 2 型糖尿病中胰岛β细胞质量减少引起的高血糖。

方法

SD 大鼠单次注射 STZ(55mg/kg)诱导β细胞破坏。然后将大鼠分为对照组、糖尿病组、GQD 组和二甲双胍组。GQD 组和二甲双胍组分别给予 GQD 提取物或二甲双胍治疗 6 周。通过免疫组织化学和免疫荧光染色检测胰岛α细胞或β细胞质量变化。通过计算机网络药理学测试 GQD 和二甲双胍对细胞增殖的潜在靶点和机制。实时 PCR 检测胰岛细胞相关基因和靶基因相关基因的表达。

结果

GQD 和二甲双胍均不能显著降低β细胞质量减少引起的 FBG 水平,但能改善肝胰腺组织病理学。GQD 和二甲双胍均未改变胰岛素阳性细胞质量,但增加了糖尿病大鼠的α细胞增殖。基因表达分析表明,GQD 和二甲双胍显著增加了细胞周期蛋白依赖性激酶 4(Cdk4)和胰岛素受体底物 1(Irs1)靶基因的水平。

结论

本研究表明,GQD 和二甲双胍通过恢复 Cdk4 和 Irs1 基因表达,显著增加了β细胞缺乏诱导的糖尿病大鼠的α细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ee9/9301855/90a3386db90c/12906_2022_3674_Fig1_HTML.jpg

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