血府逐瘀汤对气虚血瘀型慢性心力衰竭患者心肌保护及Cadherin-NrF2通路铁死亡交互作用的影响

Effect of Xuefu Zhuyu Decoction on myocardial protection and the interaction between Cadherin-NrF2 pathway and ferroptosis in patients with chronic heart failure resulting from qi deficiency and blood stasis

目的观察血府逐瘀汤对气虚血瘀型慢性心力衰竭患者心肌保护及Cadherin-NrF2通路铁死亡交互作用的影响。方法选择2021年2月至2022年5月湖州市第一人民医院治疗的气虚血瘀型心力衰竭患者100例进行病例对照研究, 分组方式为随机数字表法。50例患者为基础西医组, 给予常规治疗;50例患者为血府逐瘀汤组, 在常规治疗同时给予血府逐瘀汤治疗。两组患者均连续治疗8周, 治疗前、后检测两组患者白细胞介素13(IL-13)、细胞间黏附分子1(ICAM-1)、一氧化氮(NO)、胱抑素C(Cystatin C)、血栓素(TVB2)、可溶性白细胞分化抗原40配体(sCD40L)、血管内皮细胞钙黏蛋白(VE-cadherin)、可溶性酪氨酸激酶受体AXL(sAXL)、可溶性基质溶素2(sST2)、亚铁离子(Fe^(2+))水平, 检测谷胱甘肽过氧化物酶4(GPX4)、核因子E2相关因子2(NrF2)mRNA表达情况, 给予患者证候评分, 比较两组临床疗效。结果治疗后, 血府逐瘀汤组IL-13[(7.63±1.85)ng/L]、ICAM-1[(41.71±6.25)ng/L]、Cystatin C[(0.61±0.17)ng/L]含量均较基础西医组低[(10.56±2.13)ng/L、(50.11±8.34)ng/L、(1.03±0.22)ng/L](t=7.34、5.69、10.68, 均P<0.05);血府逐瘀汤组sCD40L[(14.61±1.19)μg/L]、TVB2[(40.18±7.24)ng/L]含量均较基础西医组低[sCD40L(16.03±1.47)μg/L、TVB2(53.37±10.16)]ng/L(t=5.30、7.47, 均P<0.05), 血府逐瘀汤组NO[(59.92±6.16)μmol/L]含量较基础西医组高[(53.17±5.49)μmol/L](t=5.78, P<0.05);血府逐瘀汤组Fe^(2+)[(0.23±0.08)μg/L]含量较基础西医组高[(0.16±0.05)μg/L](t=5.24, P<0.05), 血府逐瘀汤组VE-Cadherin[(3.02±0.72)ng/L]、NrF2 mRNA[(2.11±0.43)]、GPX4 mRNA[(4.65±0.74)]含量均较基础西医组低[(4.34±1.05)ng/L、(2.93±0.56)、(5.16±0.88)](t=7.33、8.21、3.13, 均P<0.05);血府逐瘀汤组半乳糖凝集素3(Galectin-3)[(62.48±6.09)μg/L]、sST2[(0.98±0.24)ng/L]、sAXL[(42.16±7.54)ng/L]水平均较基础西医组低[(70.96±8.15)μg/L、(1.57±0.46)ng/L、(56.11±10.02)ng/L](t=5.89、8.04、7.86, 均P<0.05);血府逐瘀汤组气短或喘息[(1.06±0.24)分]、心悸[(0.92±0.15)分]、乏力[(0.75±0.17)分]、语声低微[(0.68±0.16)分]、自汗[(0.83±0.21)分]、倦怠懒言[(0.73±0.20)分]、活动易劳累[(0.66±0.14)分]、面色或口唇紫暗[(0.61±0.16)分]评分均较基础西医组低[(1.65±0.49)分、(1.15±0.27)分、(1.16±0.31)分、(1.12±0.29)分、(1.28±0.32)分、(1.28±0.37)分、(1.01±0.21)分、(0.96±0.25)分](t=7.64、5.26、8.20、9.39、8.31、9.24、9.80、8.33, 均P<0.05);血府逐瘀汤组总有效率较基础西医组高[96.00%(48/50)比88.00%(44/50)](Z=1.91, P<0.05)。结论给予心力衰竭患者血府逐瘀汤治疗, 可抑制机体炎症反应, 改善血管内皮细胞功能, 调节Cadherin及NrF2通路, 减少氧化应激损伤, 进一步抑制铁死亡, 降低Galectin- 3、sST2、sAXL水平, 保护心肌, 缓解患者临床症状, 提升其疗效。

Objective To investigate the effect of Xuefu Zhuyu Decoction on myocardial protection and the interaction between Cadherin-NrF2 pathway and ferroptosis in patients with chronic heart failure resulting from qi deficiency and blood stasis.Methods A case-control study was conducted on 100 patients with heart failure resulting from qi deficiency and blood stasis who received treatment at The First People's Hospital of Huzhou from February 2021 to May 2022.These patients were divided into a basic western medicine group and a Xuefu Zhuyu Decoction group with 50 patients per group using the random number table method.The basic western medicine group received conventional treatment,while the Xuefu Zhuyu Decoction group received treatment with Xuefu Zhuyu Decoction in addition to conventional treatment.Both groups were treated continuously for 8 weeks.Interleukin-13,intercellular adhesion molecule-1,nitric oxide,cystatin C,thromboxane B2,soluble cluster of differentiation 40 ligand,vascular endothelial cadherin were detected before and after treatment,and soluble tyrosine kinase receptor AXL(sAXL),soluble stromal lysin-2,and ferric ion levels were determined.The mRNA expression levels of glutathione peroxidase 4 and NrF2 were detected.Syndrome scores were evaluated.Clinical efficacy was compared between the two groups.Results After treatment,the levels of interleukin-13[(7.63±1.85)ng/L],intercellular adhesion molecule-1[(41.71±6.25)ng/L],and cystatin C[(0.61±0.17)ng/L]in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group[(10.56±2.13)ng/L,(50.11±8.34)ng/L,(1.03±0.22)ng/L,t=7.34,5.69,10.68,all P<0.05].The levels of soluble cluster of differentiation 40 ligand[(14.61±1.19)μg/L]and thromboxane B2[(40.18±7.24)ng/L]in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group[(16.03±1.47)μg/L,(53.37±10.16)ng/L,t=5.30,7.47,both P<0.05],while the level of nitric oxide[(59.92±6.16)μmol/L]in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic Western medicine group[(53.17±5.49)μmol/L,t=5.78,P<0.05].The level of ferric ion[(0.23±0.08)μg/L]in the Xuefu Zhuyu Decoction group was significantly higher than that in the basic western medicine group[(0.16±0.05)μg/L,t=5.24,P<0.05].The levels of vascular endothelial cadherin[(3.02±0.72)ng/L],NrF2 mRNA[(2.11±0.43)],and glutathione peroxidase 4 mRNA[(4.65±0.74)]in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group[(4.34±1.05)ng/L,(2.93±0.56),(5.16±0.88),t=7.33,8.21,3.13,all P<0.05].The levels of Galectin-3[(62.48±6.09)μg/L],soluble stromal lysin-2[(0.98±0.24)ng/L],and sAXL[(42.16±7.54)ng/L]in the Xuefu Zhuyu Decoction group were significantly lower than those in the basic western medicine group[(70.96±8.15)μg/L,(1.57±0.46)ng/L,(56.11±10.02)ng/L,t=5.89,8.04,7.86,all P<0.05].The Xuefu Zhuyu Decoction group had lower scores for shortness of breath or wheezing[(1.06±0.24)points],palpitations[(0.92±0.15)points],fatigue[(0.75±0.17)points],low voice[(0.68±0.16)points],spontaneous sweating[(0.83±0.21)points],fatigue and laziness[(0.73±0.20)points],prone to fatigue[(0.66±0.14)points],and dark complexion or lips[(0.61±0.16)points]compared with the basic western medicine group[(1.65±0.49)points,(1.15±0.27)points,(1.16±0.31)points,(1.12±0.29)points,(1.28±0.32)points,(1.28±0.37)points,(1.01±0.21)points,(0.96±0.25)points,t=7.64,5.26,8.20,9.39,8.31,9.24,9.80,8.33,all P<0.05].The total response rate of the Xuefu Zhuyu Decoction group was significantly higher than that of the basic western medicine group[(96.00%(48/50)vs.88.00%(44/50),Z=1.91,P<0.05).Conclusion Treating patients with heart failure with Xuefu Zhuyu Decoction can inhibit inflammation,improve vascular endothelial cell function,regulate Cadherin-NrF2 pathways,reduce oxidative stress injury,further inhibit ferroptosis,reduce the levels of Galectin-3,soluble stromal lysin-2,and sAXL,protect myocardium,relieve clinical symptoms,and improve its efficacy.