[1]朱宁 项文君 周玲玲 赵旭勇.黄芩苷减轻糖尿病心肌病小鼠心功能不全的作用和机制[J].心血管病学进展,2025,(12):1145.[doi:10.16806/j.cnki.issn.1004-3934.2025.12.017]
　ZHU Ning,XIANG Wenjun,ZHOU Lingling,et al.Effect and Mechanism of Baicalin on Reducing Cardiac Dysfunction in Mice with Diabetic Cardiomyopathy[J].Advances in Cardiovascular Diseases,2025,(12):1145.[doi:10.16806/j.cnki.issn.1004-3934.2025.12.017]
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黄芩苷减轻糖尿病心肌病小鼠心功能不全的作用和机制()

《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年12期
页码:
1145
栏目:
论著
出版日期:
2025-12-25

文章信息/Info

Title:
Effect and Mechanism of Baicalin on Reducing Cardiac Dysfunction in Mice with Diabetic Cardiomyopathy
作者:
朱宁 项文君 周玲玲 赵旭勇
（温州医科大学附属第三临床学院 温州市人民医院心内科，温州 浙江 325000）
Author(s):
ZHU Ning;  XIANG Wenjun;  ZHOU Lingling;  ZHAO Xuyong
(Department of Cardiology, Third Affiliated Clinical College of Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou 325000, Zhejiang, China)
关键词:
黄芩苷; 糖尿病心肌病; 细胞焦亡; 炎症; PTPN22
Keywords:
Baicalin;  Diabetic cardiomyopathy;  Pyroptosis;  Inflammation;  PTPN22
DOI:
10.16806/j.cnki.issn.1004-3934.2025.12.017
摘要:
目的 探讨黄芩苷减轻糖尿病心肌病（DCM）的作用及其机制。方法 采用链脲佐菌素腹腔注射以建立DCM模型，并随机将小鼠分为4个处理组：对照组、模型组、黄芩苷低浓度组和黄芩苷高浓度组。采用网络药理学寻找黄芩苷治疗的靶点。酶联免疫吸附分析检测血清肌酸激酶MB同工酶（CK-MB）和乳酸脱氢酶（LDH）的表达。超声心动图用于检测小鼠心功能的变化。HE染色检测心脏病理变化。为评估心肌纤维化程度，本研究采用Masson染色法观察心肌组织形态学改变，同时通过蛋白质印迹法检测转化生长因子-β1（TGF-β1）、Ⅰ型胶原（ColⅠ）以及结缔组织生长因子（CTGF）等纤维化相关标志蛋白的表达。qRT-PCR检测C-C基序趋化因子配体20（CCL20）、集落刺激因子（CSF）1和CSF2的mRNA水平。免疫荧光染色和蛋白质印迹法检测细胞焦亡标志物GSDMD（Gasdermin D）-N的表达。蛋白质印迹法检测非受体22型蛋白酪氨酸磷酸酶（PTPN22）和肿瘤坏死因子α（TNF-α）信号通路的蛋白水平。结果 网络药理学显示黄芩苷主要的作用靶点为PTPN22和TNF-α。黄芩苷显著减少DCM小鼠心肌损伤标志物CK-MB和LDH的表达。与对照组相比，DCM组射血分数、缩短分数显著降低，左室收缩末、舒张末内径显著升高；黄芩素组较DCM组射血分数、缩短分数显著升高，左室收缩末、舒张末内径显著降低。黄芩素可显著抑制DCM小鼠心肌纤维化以及TGF-β1、ColⅠ和CTGF的高表达。黄芩苷减少DCM小鼠炎症因子CCL20、CSF1、CSF2的表达，以及GSDMD-N的表达。黄芩苷抑制DCM小鼠PTPN22和TNF-α信号通路的激活。结论 黄芩苷可能通过抑制PTPN22和TNF-α信号通路以及细胞炎症和细胞焦亡来减轻DCM小鼠心功能不全。
Abstract:
Objective To investigate the effects of baicalin on diabetic cardiomyopathy (DCM) and its underlying mechanisms. Methods A DCM model was established by intraperitoneal injection of streptozotocin and mice were randomly divided to four groups: control group, model group, low-dose baicalin group, and high-dose baicalin group. Network pharmacology was employed to identify the therapeutic targets of baicalin. The expression of serum creatine kinase MB isoenzyme (CK-MB) and lactate dehydrogenase (LDH) was measured using enzyme-linked immunosorbent assay kits. Echocardiography was performed to assess changes in cardiac function. HE staining was used to evaluate pathological changes in the heart. Myocardial tissue morphological alterations were observed using Masson’s trichrome staining, while the expression levels of fibrosis-related marker proteins, including transforming growth factor-β1 (TGF-β1),collagen type Ⅰ(Col Ⅰ),and connective tissue growth factor (CTGF),were detected by Western blot analysis. qRT-PCR was used to measure the expression levels of C-C motif chemokine ligand 20 (CCL20),colony-stimulating factor 1 (CSF1),and colony-stimulating factor 2 (CSF2). Immunofluorescence and Western blot were used to analyze the expression of the pyroptosis marker GSDMD (Gasdermin D)-N. Western blot was also employed to assess the protein levels of protein tyrosine phosphatase non-receptor type 22 (PTPN22) and TNF-α signaling pathways. Results Network pharmacology indicated that the primary targets of baicalin are PTPN22 and TNF-α. Baicalin significantly reduced the expression of myocardial injury markers CK-MB and LDH in DCM mice. Compared with the control group, the DCM group exhibited significantly decreased ejection fraction and fractional shortening, along with significantly increased left ventricular end-systolic and end-diastolic diameters. In contrast, the baicalin group showed significantly increased ejection fraction and fractional shortening, as well as significantly decreased left ventricular end-systolic and end-diastolic diameters compared to the DCM group. Baicalin significantly inhibited cardiac fibrosis in DCM mice and reduced the high expression of TGF-β1, Col I and CTGF. Baicalin reduced the expression levels of inflammatory factors CCL20,CSF1,and CSF2 in DCM mice. Baicalin also reduced the expression of GSDMD-N. Baicalin inhibited the activation of the PTPN22 and TNF-α signaling pathways in DCM mice. Conclusion Baicalin may alleviate cardiac dysfunction in DCM mice by inhibiting the PTPN22 and TNF-α signaling pathways,as well as reducing cellular inflammation and pyroptosis

参考文献/References:

[1] Shen C,Zhang Q. Forsythiaside A alleviates myocardial injury in streptozotocin-induced diabetes via endoplasmic reticulum stress-NLRP3 inflammasome pathway[J]. Int Immunopharmacol,2025,147:113956.
[2] Dillmann WH. Diabetic cardiomyopathy[J]. Circ Res,2019,124(8):1160-1162.
[3] Zhao X,Huang B,Zhang J,et al. Celastrol attenuates streptozotocin-induced diabetic cardiomyopathy in mice by inhibiting the ACE/Ang Ⅱ/AGTR1 signaling pathway[J]. Diabetol Metab Syndr,2023,15(1):186.
[4] Sun X,Wang X,He Q,et al. Investigation of the ameliorative effects of baicalin against arsenic trioxide-induced cardiac toxicity in mice[J]. Int Immunopharmacol,2021,99:108024.
[5] Chan E,Liu XX,Guo DJ,et al. Extract of Scutellaria baicalensis Georgi root exerts protection against myocardial ischemia-reperfusion injury in rats[J]. Am J Chin Med,2011,39(4):693-704.
[6] Guo L,Yang J,Yuan W,et al. Baicalein ameliorated obesity-induced cardiac dysfunction by regulating the mitochondrial unfolded protein response through NRF2 signaling[J]. Phytomedicine,2024,126:155441.
[7] Xin L,Gao J,Lin H,et al. Regulatory mechanisms of baicalin in cardiovascular diseases:a review[J]. Front Pharmacol,2020,11:583200.
[8] Zeng Y,Liao X,Guo Y,et al. Baicalin-peptide supramolecular self-assembled nanofibers effectively inhibit ferroptosis and attenuate doxorubicin-induced cardiotoxicity[J]. J Control Release,2024,366:838-848.
[9] Wang T,Wang S,Jia X,et al. Baicalein alleviates cardiomyocyte death in EAM mice by inhibiting the JAK-STAT1/4 signalling pathway[J]. Phytomedicine,2024,128:155558.
[10] Hu S,Jiang L,Yan Q,et al. Evidence construction of baicalin for treating myocardial ischemia diseases:a preclinical meta-analysis[J]. Phytomedicine,2022,107:154476.
[11] Zhao F,Fu L,Yang W,et al. Cardioprotective effects of baicalein on heart failure via modulation of Ca2+ handling proteins in vivo and in vitro[J]. Life Sci,2016,145:213-223.
[12] Tan Y,Zhang Z,Zheng C,et al. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies:preclinical and clinical evidence[J]. Nat Rev Cardiol,2020,17(9):585-607.
[13] Nakamura K,Miyoshi T,Yoshida M,et al. Pathophysiology and treatment of diabetic cardiomyopathy and heart failure in patients with diabetes mellitus[J]. Int J Mol Sci,2022,23(7):3587.
[14] Xu M,Li X,Song L. Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway[J]. Pharm Biol,2020,58(1):655-663.
[15] 冯友根,郭丽敏. 黄芩苷防治糖尿病并发症的作用与临床应用[J]. 医药导报,2004,23(8):572-573.
[16] 刘长山. 黄芩苷对糖尿病患者红细胞醛糖还原酶活性及周围神经传导速度的影响[J]. 神经科学通报(英文版),2002,18(2):555-557.
[17] 陈中华,易晓玲,李立建. 黄芩苷对急性脑梗死合并2型糖尿病患者的神经功能、血糖以及炎性因子影响[J]. 中国医药指南,2019,17(16):12-13,16.
[18] 董淑雯,孙丽萍. 黄芩苷联合胰岛素对新诊断2型糖尿病患者胰岛功能的保护作用[J]. 中国医药,2013,8(3):348-350.

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备注/Memo

备注/Memo:
基金项目（）；（2023RC271）收稿日期：2025-02-22
更新日期/Last Update: 2026-04-14