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

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.