Effect of hydrogen-rich solution on peripheral neuropathy in type 2 diabetic mice and role of silent information regulator 1
10.3760/cma.j.cn131073-20240908-00711
- VernacularTitle:富氢液对2型糖尿病小鼠周围神经病变的影响及SIRT1在其中的作用
- Author:
Shu WANG
1
;
Yang JIAO
Author Information
1. 天津市胸科医院体外循环科，天津 300000
- Publication Type:Journal Article
- Keywords:
Diabetic neuropathies;
Hydrogen;
Sirtuin 1;
MAP kinase signaling system
- From:
Chinese Journal of Anesthesiology
2025;45(7):840-845
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the effect of hydrogen-rich solution on peripheral neuropathy and the role of silent information regulator 1 (SIRT1) in type 2 diabetic mice.Methods:SPF type 2 diabetic (db/db) male mice and heterozygous non-diabetic (db/m) mice from the same litter with C57BKS background, aged 16 weeks, weighing 40-50 g, were used in this study. Thirty-two db/db mice were divided into 4 groups ( n=8 each) using the random number table method: diabetes mellitus group (db/db group), diabetes mellitus plus SIRT1 inhibitor (Ex527) group (db+ E group), diabetes mellitus plus hydrogen-rich solution group (db+ H 2 group), and diabetes mellitus plus hydrogen-rich solution plus Ex527 group (db+ H 2+ E group). Eight db/m mice were selected as non-diabetic control group (db/m group). Ex527 5 ml/kg was intraperitoneally injected once a day for 8 consecutive weeks in db+ E group and db+ H 2+ E group, and hydrogen-rich saline 5 ml/kg was intraperitoneally injected once a day for 8 consecutive weeks in db+ H 2+ E group and db+ H 2 group. The equal volume of normal saline was given instead in db/db and db/m groups. The thermal paw withdrawal latency (TWL) and motor nerve conduction velocity (MNCV) were measured before intraperitoneal injection (T 0) and at 2, 4, 6 and 8 weeks after injection (T 1-4). The animals were sacrificed, and the sciatic nerve tissue was harvested for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of SIRT1, extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cellular Jun (c-Jun), phosphorylated c-Jun (p-c-Jun) (by Western blot). Results:Compared to db/m group, the TWL was significantly prolonged and MNCV was reduced at T 0-4, the expression of SIRT1 was down-regulated, and the ratios of p-ERK/ERK and p-c-Jun/c-Jun were increased in db/db group ( P<0.05). Compared to db/db group, the TWL was significantly shortened and MNCV was accelerated at T 1-4, the expression of SIRT1 was up-regulated, and the ratios of p-ERK/ERK and p-c-Jun/c-Jun were decreased in db+ H 2 group, and the TWL was significantly prolonged and MNCV was reduced at T 1-4, the expression of SIRT1 was down-regulated, and the ratios of p-ERK/ERK and p-c-Jun/c-Jun were increased in db+ E group ( P<0.05). Compared to db+ H 2 group, the TWL was significantly prolonged and MNCV was reduced at T 1-4, the expression of SIRT1 was down-regulated, and the ratios of p-ERK/ERK and p-c-Jun/c-Jun were increased in db+ H 2+ E group ( P<0.05). The myelin sheath thickness was irregular, with focal disintegration and fracturing, manifesting as vacuolar changes and demyelination along with axonal dropout in db/db group, db+ E group and db+ H 2+ E group, and myelin lesions were significantly reduced in db+ H 2 group. Conclusions:The mechanism by which hydrogen-rich saline ameliorates peripheral neuropathy may be related to up-regulating the expression of SIRT1 and inhibiting the activation of ERK/c-Jun signaling pathway in type 2 diabetic mice.
