活血潜阳祛痰方抑制铁死亡改善肥胖高血压大鼠心肌重构的研究OA
Inhibition of Ferroptosis and Improvement of Myocardial Remodeling in Obese Hypertensive Rats by Huoxue Qianyang Qutan Recipe
目的 在临床确有疗效的基础上,明确活血潜阳祛痰方(Huoxue Qianyang Qutan Recipe,HQQR)抑制铁死亡改善肥胖高血压(Obesity hypertension,OBH)心肌重构的疗效.方法 通过高脂饮食喂养自发性高血压大鼠(Spontaneously hypertensive rats,SHR)建立OBH模型,将成功造模的OBH大鼠随机分为模型组(OBH)、HQQR低剂量组(HQQR-L,19.35 g生药/kg/d)、高剂量组(HQQR-H,38.7 g生药/kg/d)和缬沙坦组(Valsartan,30 mg/kg/d),并以普通饲料喂养的SHR和京都种大鼠作为对照.药物干预10周后,对大鼠进行体重、Lee's指数、肝指数、血压、糖脂代谢及心室重构指标测定;通过HE和Masson染色观察心肌组织病理学变化;生化检测铁离子(Fe2+)及谷胱甘肽(Glutathione,GSH)含量;进一步应用RT-qPCR和Western blot检测心肌组织中铁死亡标志物溶质载体家族7成员11(Solute carrier family 7 member 11,SLC7A11)及谷胱甘肽过氧化物酶4(Glutathione peroxidase 4,GPX4)的mRNA和蛋白表达水平.结果 造模成功后的OBH大鼠表现出典型的肥胖、高血压、糖脂代谢紊乱,心肌重构改变,心肌细胞水肿和纤维化程度严重.且心肌组织中Fe²⁺蓄积显著,GSH、SLC7A11和GPX4的含量显著降低.HQQR治疗后,大鼠的体重、Lee's指数、肝指数及血压显著降低(P<0.05),糖脂代谢紊乱明显改善(P<0.05);心室重构改善(P<0.05);心肌细胞形态改善,纤维化程度显著减少(P<0.05);Fe2+水平显著降低(P<0.05),而GSH水平显著升高(P<0.05);并在基因和蛋白水平验证SLC7A11及GPX4的mRNA及蛋白表达均显著上调(P<0.05),呈剂量依赖性.结论 活血潜阳祛痰方可能通过抑制铁死亡改善肥胖高血压大鼠的心肌重构.
Objective To evaluate the efficacy of Huoxue Qianyang Qutan Recipe(HQQR),a clinically proven traditional Chinese medicine formula,in attenuating myocardial remodeling in obesity hypertension(OBH)rats by inhibiting ferroptosis.Methods A rat model of OBH was established by feeding spontaneously hypertensive rats(SHR)by a high-fat diet.Successfully modeled OBH rats were randomly divided into the model group(OBH),low-dose HQQR group(HQQR-L,19.35 g crude drug/kg/d),high-dose HQQR group(HQQR-H,38.7 g crude drug/kg/d),and valsartan group(30 mg/kg/d).Age-matched SHR and Wistar Kyoto rats fed a standard diet served as controls.After 10 weeks of drug intervention,body weight,Lee's index,liver index,blood pressure,glucose and lipid metabolism parameters,and indices of myocardial remodeling were measured.Myocardial pathological changes were observed by HE and Masson's trichrome staining.Biochemical assays were used to detect myocardial levels of ferrous ion(Fe²⁺)and glutathione(GSH).Additionally,the mRNA and protein expression levels of ferroptosis-related markers,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),were measured by RT-qPCR and Western blot,respectively.Results OBH rats exhibited typical symptoms of obesity,hypertension,metabolic dysregulation,and significant myocardial remodeling,characterized by cardiomyocyte edema and extensive fibrosis.Fe²⁺ accumulation markedly increased in myocardial tissue,while levels of GSH,SLC7A11,and GPX4 significantly reduced.Treatment with HQQR significantly decreased body weight,Lee's index,liver index,and blood pressure(P<0.05),improved glucose and lipid metabolism(P<0.05),alleviated myocardial remodeling(P<0.05),reduced myocardial fibrosis,and ameliorated cardiomyocyte morphology(P<0.05).Furthermore,HQQR significantly reduced Fe²⁺ levels(P<0.05),increased GSH levels(P<0.05),and upregulated the mRNA and protein expression of SLC7A11 and GPX4 in a dose-dependent manner(P<0.05).Conclusion HQQR may ameliorate myocardial remodeling in OBH rats by inhibiting ferroptosis,likely through the activation of the SLC7A11/GPX4 pathway.
赵妤修;马玉龙;芦波;李达;陈晓喆;王明珠;符德玉
上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437上海中医药大学附属岳阳中西医结合医院 上海 200437
医药卫生
活血潜阳祛痰方肥胖高血压铁死亡心肌重构
Huoxue Qianyang Qutan recipeObesity hypertensionFerroptosisMyocardial remodeling
《世界科学技术-中医药现代化》 2026 (1)
153-163,11
国家自然科学基金委员会面上项目(82174130):基于线粒体自噬与NLRP3炎性小体crosstalk探讨活血潜阳祛痰方改善OBH心肌损害的机制研究,负责人:符德玉国家自然科学基金委员会面上项目(82274262):活血潜阳祛痰方调控FUNDC1-MAM-线粒体Ca2+稳态改善OBH心肌重构的机制研究,负责人:芦波上海市白玉兰人才计划浦江项目(24PJD113):基于线粒体内质网Ca2+转运介导的铁死亡探讨活血潜阳祛痰方对OBH心肌重构的干预机制,负责人:芦波.
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