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二氢杨梅素通过抑制糖尿病大鼠的高迁移率族蛋白B1改善心脏功能不全

[Dihydromyricetin improves cardiac insufficiency by inhibiting HMGB1 in diabetic rats].

作者信息

Liu S, Liu Q, Peng Q, Zhang Y, Wang J

机构信息

Department of Pharmacology, Xiangnan University, Chenzhou 423000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2022 May 20;42(5):641-648. doi: 10.12122/j.issn.1673-4254.2022.05.03.

DOI:10.12122/j.issn.1673-4254.2022.05.03
PMID:35673906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9178629/
Abstract

OBJECTIVE

To investigate the effect of dihydromyricetin (DHM) on cardiac insufficiency in diabetic rats and explore the underlying mechanism.

METHOD

Twenty-four male SD rats were randomized equally into normal control group, type 2 diabetes (T2DM) group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin (STZ) injection, metformin (MET) group with daily intragastric administration of MET (150 mg/kg) for 8 weeks after T2DM modeling, and dihydromyricetin (DHM) group with daily intragastric administration of DHM (250 mg/kg) for 8 weeks after modeling. The levels of fasting blood glucose, low density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C) and glycosylated hemoglobin (HbA1c) of the rats were measured, and plasma levels of insulin and high mobility group protein-1 (HMGB1) were detected with ELISA. The cardiac function of the rats was assessed using color echocardiography, ECG was measured using a biological signal acquisition system, and myocardial pathology was observed with HE staining. The protein expressions of HMGB1, nuclear factor-κB (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in the myocardial tissue were detected using Western blotting.

RESULTS

Compared with the control group, the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1, NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue ( < 0.05 or 0.01). Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats ( < 0.05 or 0.01), decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue ( < 0.05 or 0.01).

CONCLUSION

DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.

摘要

目的

探讨二氢杨梅素(DHM)对糖尿病大鼠心功能不全的影响并探究其潜在机制。

方法

将24只雄性SD大鼠随机均分为正常对照组、给予高糖高脂饮食并低剂量注射链脲佐菌素(STZ)6周的2型糖尿病(T2DM)组、T2DM建模后每日灌胃给予二甲双胍(MET,150 mg/kg)8周的二甲双胍组以及建模后每日灌胃给予二氢杨梅素(DHM,250 mg/kg)8周的二氢杨梅素组。检测大鼠空腹血糖、低密度脂蛋白(LDL-C)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)和糖化血红蛋白(HbA1c)水平,采用酶联免疫吸附测定法(ELISA)检测血浆胰岛素和高迁移率族蛋白1(HMGB1)水平。使用彩色超声心动图评估大鼠心功能,采用生物信号采集系统测量心电图,并通过苏木精-伊红(HE)染色观察心肌病理学变化。采用蛋白质印迹法检测心肌组织中HMGB1、核因子κB(NF-κB)p65和磷酸化NF-κB p65(p-NF-κB p65)的蛋白表达。

结果

与对照组相比,T2DM组大鼠建模后心功能出现明显异常,血浆HMGB1水平显著升高,心肌组织中HMGB1、NF-κB p65和p-NF-κB p65蛋白表达增加(P<0.05或0.01)。二氢杨梅素治疗显著改善了糖尿病大鼠的心功能指标(P<0.05或0.01),降低了血浆HMGB1水平,并下调了心肌组织中HMGB1和p-NF-κB p65的蛋白表达(P<0.

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