二甲双胍提高了各种小鼠器官中的组织内硫化氢浓度。

Metformin raises hydrogen sulfide tissue concentrations in various mouse organs.

机构信息

Department of Human Developmental Biology, Jagiellonian University Medical College, Kraków, Poland.

出版信息

Pharmacol Rep. 2013;65(3):737-42. doi: 10.1016/s1734-1140(13)71053-3.

DOI:10.1016/s1734-1140(13)71053-3

PMID:23950598

Abstract

BACKGROUND

The epidemic of diabetes mellitus type 2 forces to intensive work on the disease medication. Metformin, the most widely prescribed insulin sensitizer, exerts pleiotropic actions on different tissues by not fully recognized mechanisms. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals and is perceived as a potential agent in the treatment of different disorders. The interaction between biguanides and H2S is unknown. The aim of the study is to assess the influence of metformin on the H2S tissue concentrations in different mouse organs.

METHODS

Adult SJL female mice were administered intraperitoneally 100 mg/kg b.w. per day of metformin (group D1, n = 6) or 200 mg/kg b.w. per day of metformin (group D2, n = 7). The control group (n = 6) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with Siegel spectrophotometric modified method.

RESULTS

There was a significant progressive increase in the H2S concentration along with the rising metformin doses as compared to the control group in the brain (D1 by 103.6%, D2 by 113.5%), in the heart (D1 by 11.7%, D2 by 27.5%) and in the kidney (D1 by 7.1%, D2 by 9.6%). In the liver, massive H2S accumulation was observed in the group D1 (increase by 420.4%), while in the D2 group only slight H2S level enhancement was noted (by 12.5%).

CONCLUSION

Our experiment has shown that metformin administration is followed by H2S tissue concentrations increase in mouse brain, heart, kidney and liver.

摘要

背景

2 型糖尿病的流行迫使人们对该疾病的药物治疗进行深入研究。二甲双胍是最广泛应用的胰岛素增敏剂，通过尚未完全明确的机制对不同组织发挥多种作用。在哺乳动物的各个系统中，硫化氢（H2S）参与生理和病理生理过程，被认为是治疗各种疾病的潜在药物。二甲双胍与 H2S 之间的相互作用尚不清楚。本研究旨在评估二甲双胍对不同小鼠器官中 H2S 组织浓度的影响。

方法

成年 SJL 雌性小鼠每天腹腔注射 100mg/kg（D1 组，n=6）或 200mg/kg（D2 组，n=7）的二甲双胍。对照组（n=6）给予生理盐水。采用 Siegel 分光光度法改良法测量游离酸不稳定 H2S 组织浓度。

结果

与对照组相比，随着二甲双胍剂量的增加，脑组织（D1 组增加 103.6%，D2 组增加 113.5%）、心脏（D1 组增加 11.7%，D2 组增加 27.5%）和肾脏（D1 组增加 7.1%，D2 组增加 9.6%）中 H2S 浓度呈显著递增趋势。在肝脏中，D1 组观察到大量 H2S 积聚（增加 420.4%），而 D2 组仅观察到 H2S 水平略有增加（增加 12.5%）。