心力衰竭存在高发病率、高病死率的特征,寻求针对心力衰竭的有效治疗策略并进一步提升临床疗效一直是重要的研究方向。炎症失衡已被证明是心力衰竭的重要病理环节之一,与心功能障碍、心肌纤维化等不良事件呈正相关。近些年研究证实NOD...心力衰竭存在高发病率、高病死率的特征,寻求针对心力衰竭的有效治疗策略并进一步提升临床疗效一直是重要的研究方向。炎症失衡已被证明是心力衰竭的重要病理环节之一,与心功能障碍、心肌纤维化等不良事件呈正相关。近些年研究证实NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain-associated protein 3,NLRP3)炎症小体激活在不同因素诱导心力衰竭的炎症失衡环节中具有共性调控机制,并且部分中药及其有效成分能够显著抑制NLRP3炎症小体激活而改善心力衰竭。该文首先概述了NLRP3炎症小体的基本情况,然后总结了NLRP3炎症小体在不同因素诱导心力衰竭中的调控机制,最后介绍了近年来抑制NLRP3炎症小体而改善心力衰竭的中药及有效成分的研究进展,以期为中西医结合防治心力衰竭的创新药物研究提供参考。展开更多
Yi-Qi-Huo-Xue Decoction(YQHX)is the recombination of Dang-Gui-Bu-Xue Decoction(DBD),which is one of the well-known traditional Chinese Medicine(TCM)prescription,and has long been shown to have significant protective e...Yi-Qi-Huo-Xue Decoction(YQHX)is the recombination of Dang-Gui-Bu-Xue Decoction(DBD),which is one of the well-known traditional Chinese Medicine(TCM)prescription,and has long been shown to have significant protective effects against myocardial ischemic injury.In previous studies,we found that YQHX could regulate lipid and glucose metabolism,promote angiogenesis,attenuate inflammatory response,and ameliorate left ventricular function in myocardial ischemia rat models.However,the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far.In this study,the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9 c2 cell injury model.YQHX(8.2 g·kg-1)and positive-control drug trimetazidine(10 mg·kg-1)were administered daily on the second day after left anterior descending(LAD)operation.At 7 days and 28 days after surgery,changes of cardiac morphology,structure,and function were evaluated by H&E staining and echocardiography,respectively.The plasma lipid levels and mitochondrial ATP content were also evaluated.Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK,PGC-1α,CPT-1α,and PPARα.YQHX improved cardiac function and ameliorated lipid metabolism disorders.Furthermore,YQHX increased the expression of p-AMPK,PGC-1α,and CPT-1αwithout changing PPARαin ischemic rat myocardium.In vitro,YQHX activated the protein and mRNA expression of PGC-1α,CPT-1α,and PPARαin hypoxia-induced H9 c2 cells injury,whereas AMPK inhibitor Compound c blocked the effects of YQHX.Taken together,the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.展开更多
文摘心力衰竭存在高发病率、高病死率的特征,寻求针对心力衰竭的有效治疗策略并进一步提升临床疗效一直是重要的研究方向。炎症失衡已被证明是心力衰竭的重要病理环节之一,与心功能障碍、心肌纤维化等不良事件呈正相关。近些年研究证实NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain-associated protein 3,NLRP3)炎症小体激活在不同因素诱导心力衰竭的炎症失衡环节中具有共性调控机制,并且部分中药及其有效成分能够显著抑制NLRP3炎症小体激活而改善心力衰竭。该文首先概述了NLRP3炎症小体的基本情况,然后总结了NLRP3炎症小体在不同因素诱导心力衰竭中的调控机制,最后介绍了近年来抑制NLRP3炎症小体而改善心力衰竭的中药及有效成分的研究进展,以期为中西医结合防治心力衰竭的创新药物研究提供参考。
基金the National Natural Science Foundation of China(No.81473552)the China Postdoctoral Science Foundation(No.2019TQ0043)。
文摘Yi-Qi-Huo-Xue Decoction(YQHX)is the recombination of Dang-Gui-Bu-Xue Decoction(DBD),which is one of the well-known traditional Chinese Medicine(TCM)prescription,and has long been shown to have significant protective effects against myocardial ischemic injury.In previous studies,we found that YQHX could regulate lipid and glucose metabolism,promote angiogenesis,attenuate inflammatory response,and ameliorate left ventricular function in myocardial ischemia rat models.However,the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far.In this study,the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9 c2 cell injury model.YQHX(8.2 g·kg-1)and positive-control drug trimetazidine(10 mg·kg-1)were administered daily on the second day after left anterior descending(LAD)operation.At 7 days and 28 days after surgery,changes of cardiac morphology,structure,and function were evaluated by H&E staining and echocardiography,respectively.The plasma lipid levels and mitochondrial ATP content were also evaluated.Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK,PGC-1α,CPT-1α,and PPARα.YQHX improved cardiac function and ameliorated lipid metabolism disorders.Furthermore,YQHX increased the expression of p-AMPK,PGC-1α,and CPT-1αwithout changing PPARαin ischemic rat myocardium.In vitro,YQHX activated the protein and mRNA expression of PGC-1α,CPT-1α,and PPARαin hypoxia-induced H9 c2 cells injury,whereas AMPK inhibitor Compound c blocked the effects of YQHX.Taken together,the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.
