SIRT1对糖尿病胃轻瘫小鼠胃排空的影响及机制

doi:10.3969/j.issn.1006-7795.2020.04.015

摘要/Abstract

摘要： 目的研究沉默信息调节因子1（silent information regulator 1，SIRT1）对糖尿病胃轻瘫小鼠胃排空率的影响及机制。方法雄性C57BL/6J小鼠采用数字法随机分为空白组、模型组、溶剂对照组、白藜芦醇（resveratrol，Res）组，每组8只。除空白组以外，其余小鼠一次性腹腔注射链脲佐菌素（streptozotocin，STZ）造模，空白组小鼠给予等量的柠檬酸缓冲液腹腔注射。造模成功后，Res组小鼠给予Res 30 mg·kg^-1·d^-1腹腔注射，溶剂对照组小鼠给予等量DMSO0.9%（质量分数）氯化钠注射液溶液腹腔注射，持续6周。6周后采用固体胃排空法测胃排空率，比色法检测小鼠胃窦组织中总超氧化物歧化酶（total superoxide dismutase，T-SOD）和丙二醛（malondialdehyde，MDA）浓度，免疫组织化学染色和蛋白免疫印迹法（Western blotting，WB）检测胃窦组织中SIRT1、BTB-CNC异体同源体1（BTB and CNC homology 1，Bach1）、酪氨酸激酶受体（tyrosine kinase receptor，c-kit）和血红蛋白氧合酶-1（heme oxygenase-1，HO-1）的表达变化。结果与空白组小鼠相比，模型组小鼠胃排空率明显下降，与模型组小鼠相比，Res组小鼠胃排空率明显升高（P<0.05）；与空白组小鼠相比，模型组小鼠胃窦组织中T-SOD活力下降，MDA含量升高，与模型组小鼠相比，Res组小鼠T-SOD活力升高，MDA含量下降（P<0.05）；模型组小鼠胃窦组织中SIRT1、c-kit、HO-1较空白组下降，而Bach1浓度高于空白组；Res组小鼠SIRT1、c-kit、HO-1均较模型组上升，而Bach1浓度低于模型组（P<0.05）。结论上调SIRT1可以通过调控Bach1和HO-1蛋白浓度，减轻糖尿病胃轻瘫小鼠胃组织中的氧化应激，维持小鼠正常的胃排空。

关键词: 糖尿病胃轻瘫, 沉默信息调节因子1, BTB-CNC异体同源体1

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

中图分类号:

R587.2

郑晗, 周冬梅, 苗蓓, 李伟. SIRT1对糖尿病胃轻瘫小鼠胃排空的影响及机制[J]. 首都医科大学学报, 2020, 41(4): 590-596.

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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