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 Guangzhou 510000, China.
Department of Cardiovascular Medicine, Heart Center Laboratory, Zhujiang Hospital, Southern Medical University Guangzhou 510282, China.
Zhongguo Zhong Yao Za Zhi. 2022 May;47(10):2705-2711. doi: 10.19540/j.cnki.cjcmm.20211201.401.
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.
本研究旨在探讨葛根芩连汤（GQD）对湿热证糖尿病小鼠心功能的影响及其作用机制。将db/db糖尿病小鼠置于湿热环境试验箱中以诱导湿热证。48只6周龄的db/db小鼠随机分为6组，即db/db糖尿病模型组、湿热证db/db糖尿病小鼠（db/db-dh）组、低剂量GQD治疗的湿热证db/db糖尿病小鼠（db/db-dh+GQD-L）组、db/db-dh+GQD-M（中剂量）组、db/db-dh+GQD-H（高剂量）组，以及db/db-dh+lipro（铁死亡抑制剂脂抑素-1）组，另将8只6周龄的db/m小鼠分为对照组。结果显示，小鼠在暴露于“高脂饮食”和“湿热环境”后出现湿热证，表现为空腹血糖升高、食量减少、尿量减少、腹泻、精神萎靡、毛发稀疏粗糙、皮毛暗黄无光泽。然而，高剂量GQD灌胃10周可改善上述症状，抑制心肌肥大和纤维化，并改善db/db-dh小鼠的心脏舒张功能。qPCR结果表明，与db/db-dh组相比，GQD可调节铁死亡相关基因的表达，减弱心肌中的脂质过氧化，并上调谷胱甘肽过氧化物酶4（GPX4）的表达。同时，铁死亡抑制剂脂抑素-1可显著改善db/db-dh小鼠的心功能并逆转心脏重塑。可以得出结论，湿热证可能加重db/db小鼠的心肌铁死亡并加速心脏重塑，从而导致舒张功能障碍。GQD能够改善湿热证糖尿病小鼠的心脏重塑和舒张功能，这可能与其抑制心肌铁死亡有关。
