Effect and mechanism of SIRT1 on gastric emptying in diabetic gastroparesis mice

doi:10.3969/j.issn.1006-7795.2020.04.015

Abstract

Abstract: Objective To study the effect and mechanism of silent information regulator 1 (SIRT1) on gastric emptying in diabetic gastroparesis mice. Methods Thirty-two male C57BL/6J mice were randomly divided into experimental groups (n=24) and blank group (n=8) after one week of adaptive feeding. The experimental group was given a single intraperitoneal injection of streptozotocin(STZ) at 160 mg/kg to establish an animal model of diabetes. The blank group was given an intraperitoneal injection of equal amount of sodium citrate buffer. After successful modeling, the mice in the experimental group were randomly divided into a model group, a solvent control group and a resveratrol (Res) group, with 8 mice in each group. The Res group was given the SIRT1 activator Res intraperitoneally at a dose of 30 mg/kg, the solvent control group was given the same amount of DMSO and normal saline intraperitoneally once a day for 6 weeks. The general conditions of the mice in each group were observed. The gastric emptying rate was measured with solid gastric emptying method. Oxidative stress-related factors in the gastric tissues of mice such as total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) content were measured by colorimetric method. Immunohistochemical staining (IHC) and Western blotting (WB) were used to detect the expressions of SIRT1, BTB-CNC homolog 1 (Bach1), tyrosine kinase receptor (c-kit), and heme oxygenase-1 (HO-1) in gastric tissues. Results Compared with the blank group, the gastric emptying rate of the model group decreased (P<0.05). Compared with the model group, the gastric emptying rate of the Res group increased (P<0.05). Compared with the blank group, the content of MDA increased and the activity of T-SOD decreased in the gastric tissue of the Res group (P<0.05). Compared with the model group, the content of MDA decreased and the activity of T-SOD increased in the gastric tissue of the Res group(P<0.05). Compared with the blank group, the SIRT1, c-kit, HO-1 protein levels in the gastric tissue of the model group decreased, while the Bach1 protein level increased(P<0.05). Compared with the model group, the SIRT1, c-kit, HO-1 protein levels in the gastric tissue of the Res group increased, while the Bach1 protein level decreased (P<0.05). Conclusion Up-regulating SIRT1 can reduce the oxidative stress in the gastric tissues of diabetic gastroparesis mice and maintain normal gastric emptying of diabetic mice by regulating Bach1 and HO-1 protein levels.

Key words: diabetic gastroparesis, silent information regulator 1(SIRT1), Bach1

CLC Number:

R587.2

Zheng Han, Zhou Dongmei, Miao Bei, Li Wei. Effect and mechanism of SIRT1 on gastric emptying in diabetic gastroparesis mice[J]. Journal of Capital Medical University, 2020, 41(4): 590-596.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2020.04.015

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2020/V41/I4/590

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