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2022, v.47(10) 2705-2711

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葛根芩连汤对糖尿病湿热型小鼠心脏舒张功能的影响
Effect of Gegen Qinlian Decoction on cardiac diastolic function of diabetic mice with damp-heat syndrome

余洁英;林育浩;周凤华;刘海琼;邓广辉;程赛博;王先宝;
YU Jie-ying;LIN Yu-hao;ZHOU Feng-hua;LIU Hai-qiong;DENG Guang-hui;CHENG Sai-bo;WANG Xian-bao;School of Traditional Chinese Medicine, Southern Medical University;Department of Cardiovascular Medicine, Heart Center Laboratory, Zhujiang Hospital, Southern Medical University;Basic Teaching and Research Office of Integrated Traditional Chinese and Western Medicine, School of Traditional Chinese Medicine, Southern Medical University;

摘要(Abstract):

该文拟探究葛根芩连汤对糖尿病湿热型小鼠心脏功能的影响及机制。选择db/db小鼠作为糖尿病模型,并在其基础上应用湿热环境实验箱构建湿热证模型;将48只6周龄db/db小鼠随机分为6组:db/db(糖尿病小鼠模型组)、db/db-dh(湿热型糖尿病小鼠模型组)、db/db-dh+GQD-L(葛根芩连汤低剂量组)、db/db-dh+GQD-M(葛根芩连汤中剂量组)、db/db-dh+GQD-H(葛根芩连汤高剂量组)、db/db-dh+lipro (liproxstatin-1,铁死亡抑制剂组),并以8只6周龄db/m小鼠作为对照组。结果表明,通过“高脂饮食”与“湿热环境”综合因素的影响,小鼠出现了空腹血糖升高、饮食减少、小便量减少、大便溏泄、精神萎靡、毛发疏松粗糙、毛色暗黄无光泽等湿热症状。而高剂量的葛根芩连汤灌胃处理10周可显著缓解db/db-dh小鼠的上述症状,并抑制心肌细胞肥大及纤维化,进而改善小鼠的心脏舒张功能;qPCR结果提示葛根芩连汤可调控铁死亡相关基因的表达,并减轻心肌组织脂质过氧化水平、上调GPX4 (glutathione peroxidase 4)蛋白表达;同时,铁死亡抑制剂liproxstatin-1可显著改善db/db-dh小鼠心脏功能及逆转心肌重构。由此得出结论:湿热证可能通过促进心肌细胞铁死亡加速db/db小鼠心脏重构进程,进而导致舒张功能障碍;葛根芩连汤能改善糖尿病湿热型小鼠心脏重构及舒张功能,可能与抑制心肌细胞铁死亡有关。
This study was designed to explore the effect and mechanism of Gegen Qinlian Decoction(GQD) on cardiac function of diabetic mice with damp-heat syndrome. The db/db diabetic mice were exposed to the damp-heat environment test chamber for inducing the damp-heat syndrome. Forty-eight six-week-old db/db mice were randomly divided into six groups, namely the db/db diabetic model group, db/db diabetic mouse with damp-heat syndrome(db/db-dh) group, db/db diabetic mouse with damp-heat syndrome treated with low-dose GQD(db/db-dh+GQD-L) group, db/db-dh+GQD-M(medium-dose) group, db/db-dh+GQD-H(high-dose) group, and db/db-dh+lipro(liprostatin-1, the inhibitor of ferroptosis) group, with eight six-week-old db/m mice classified into the control group. The results showed that mice presented with the damp-heat syndrome after exposure to the "high-fat diet" and "damp-heat environment", manifested as the elevated fasting blood glucose, reduced food intake, low urine output, diarrhea, listlessness, loose and coarse hair, and dark yellow and lusterless fur. However, the intragastric administration of the high-dose GQD for 10 weeks ameliorated the above-mentioned symptoms, inhibited myocardial hypertrophy and fibrosis, and improved the cardiac diastolic function of db/db-dh mice. qPCR suggested that GQD regulated the expression of ferroptosis-related genes, weakened the lipid peroxidation in the myocardium, and up-regulated glutathione peroxidase 4(GPX4) expression in comparison with those in the db/db-dh group. At the same time, the ferroptosis inhibitor liprostatin-1 significantly improved the cardiac function and reversed the cardiac remodeling of db/db-dh mice. It can be concluded that the damp-heat syndrome may aggravate myocardial ferroptosis and accelerate cardiac remodeling of db/db mice, thus leading to diastolic dysfunction. GQD is able to improve cardiac remodeling and diastolic function in diabetic mice with damp-heat syndrome, which may be related to its inhibition of myocardial ferroptosis.

关键词(KeyWords): 葛根芩连汤;湿热证;糖尿病;心脏舒张功能;铁死亡
Gegen Qinlian Decoction(GQD);damp-heat syndrome;diabetes;cardiac diastolic function;ferroptosis

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(81774213);; 广东省自然科学基金面上项目(2019A1515010655,2021A1515011097)

作者(Authors): 余洁英;林育浩;周凤华;刘海琼;邓广辉;程赛博;王先宝;
YU Jie-ying;LIN Yu-hao;ZHOU Feng-hua;LIU Hai-qiong;DENG Guang-hui;CHENG Sai-bo;WANG Xian-bao;School of Traditional Chinese Medicine, Southern Medical University;Department of Cardiovascular Medicine, Heart Center Laboratory, Zhujiang Hospital, Southern Medical University;Basic Teaching and Research Office of Integrated Traditional Chinese and Western Medicine, School of Traditional Chinese Medicine, Southern Medical University;

DOI: 10.19540/j.cnki.cjcmm.20211201.401

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