基于Nrf2/HO-1通路探讨藏红花酸对高血脂合并冠心病大鼠心肌损伤的改善作用及对心电图的影响

Effects of Crocetin on Myocardial Injury and Electrocardiogram in Hyperlipidemic Rats with Coronary Heart Disease Based on Nrf2/HO-1 Pathway

目的:探究藏红花酸通过Nrf2/HO-1通路对高血脂合并冠心病大鼠心肌损伤的改善作用和对心电图的影响。方法:建立高血脂合并冠心病大鼠模型。建模成功大鼠随机分为模型组、消心痛组、藏红花酸组、藏红花酸+ML385组,同时设对照组。心电图检查各组大鼠ST段偏移幅度;比较血脂指标;TUNEL染色观察心肌细胞凋亡情况;Western blotting检测心肌组织Nrf2、HO-1、Bcl-2、Bax蛋白的表达。结果:模型组大鼠心电图ST段偏移幅度,血清中TG、TC、LDL-C水平,心肌细胞AI,以及心肌组织Bax蛋白相对表达量均高于对照组,HDL-C水平,Nrf2、HO-1、Bcl-2蛋白相对表达量均低于对照组(P<0.05);消心痛组、藏红花酸组大鼠心电图ST段偏移幅度,血清中TG、TC、LDL-C水平,心肌细胞AI,以及心肌组织Bax蛋白相对表达量低于模型组,HDL-C水平,Nrf2、HO-1、Bcl-2蛋白相对表达量均高于模型组(P<0.05);藏红花酸+ML385组大鼠心电图ST段偏移幅度,血清中TG、TC、LDL-C、HDL-C水平,心肌细胞AI,以及心肌组织Nrf2、HO-1、Bcl-2、Bax蛋白相对表达量与模型组比较,差异均无统计学意义(P>0.05);藏红花酸组大鼠心电图ST段偏移幅度,血清中TG、TC、LDL-C水平,心肌细胞AI,以及心肌组织Bax蛋白相对表达量均高于消心痛组,HDL-C水平,Nrf2、HO-1、Bcl-2蛋白相对表达量均低于消心痛组(P<0.05);藏红花酸+ML385组大鼠心电图ST偏移幅度,血清中TG、TC、LDL-C水平,心肌细胞AI,以及心肌组织Bax蛋白相对表达量均高于藏红花酸组,HDL-C水平,Nrf2、HO-1、Bcl-2蛋白相对表达量均低于藏红花酸组(P<0.05)。结论:藏红花酸对高血脂合并冠心病大鼠血脂代谢及心肌损伤有改善作用,并能抑制心肌细胞凋亡,其机制可能与激活Nrf2/HO-1信号通路有关。

Objective:To explore the effect of crocetin on myocardial injury in rats with hyperlipidemia and coronary heart disease through the Nrf2/HO-1 pathway and its influence on the electrocardiogram(ECG).Methods:Establish a rat model of hyperlipidemia combined with coronary heart disease.Successfully modeled rats were randomly divided into model group,Xiaoxintong group,crocetin group,crocetin+ML385 group,and a control group.ECG was used to detect ST segment deviation.Blood lipid indexes were compared.TUNEL staining was used to observe cardiomyocyte apoptosis.Western blotting was used to detect the expression of Nrf2,HO-1,Bcl-2 and Bax protein.Results:The ST segment deviation amplitude of the ECG,the levels of TG,TC,LDL-C in serum,and the relative expressions of AI and Bax in myocardial cells of model group were higher than those of control group,while the levels of HDL-C and the relative expressions of Nrf2,HO-1 and Bcl-2 in model group were lower than those of control group(P<0.05).The ST segment deviation amplitude of ECG,the levels of TG,TC and LDL-C in serum,the relative expression of AI and Bax in myocardial cells of rats in Xiaoxintong group and crocetin group were lower than those in model group,while the levels of HDL-C,the relative expression of Nrf2,HO-1 and Bcl-2 in myocardial cells of rats in Xiaoxintong group and crocetin group were higher than those in model group(P<0.05).There were no significant differences in ST segment deviation amplitude of ECG,serum TG,TC,LDL-C,HDL-C levels and relative expression of AI,Nrf2,HO-1,Bcl-2,Bax proteins between crocetin+ML385 group and model group(P>0.05).The ST segment deviation amplitude of ECG,the levels of TG,TC,LDL-C in serum,the relative expression of AI and Bax in myocardial cells of rats in the crocetin group were higher than in the Xiaoxintong group,while the levels of HDL-C,the relative expression of Nrf2,HO-1 and Bcl-2 in myocardial cells of rats in crocetin group were lower than Xiaoxintong group(P<0.05).The ST segment deviation amplitude of ECG,the levels of TG,TC,LDL-C in serum,the relative expression of AI and Bax in myocardial cells of rats in crocetin+ML385 group were higher than in the crocetin group,while the levels of HDL-C,the relative expression of Nrf2,HO-1 and Bcl-2 in myocardial cells of rats in crocetin+ML385 group were lower than the crocetin group(P<0.05).Conclusion:Crocetin can improve blood lipid metabolism and myocardial damage in rats with hyperlipidemia and coronary heart disease,and can inhibit cardiomyocyte apoptosis.The mechanism may be related to the activation of Nrf2/HO-1 signaling pathway.