鹿角方调控NF-κB通路抑制血管紧张素Ⅱ诱导的心肌细胞肥大  

Lujiao Formula Inhibiting Cardiac Hypertrophy Induced by AngⅡthrough Regulating the NF-κB Pathways

在线阅读下载全文

作  者:张建伟[1] 刘力[1] 徐光临[1] 时潇丽 ZHANG Jianwei;LIU Li;XU Guanglin;SHI Xiaoli(Third Grade Laboratory of TCM Preparations,National Administration of Traditional Chinese Medicine(TCM),Shuguang Hospital Affiliated to Shanghai University of TCM,Shanghai 201203,China)

机构地区:[1]上海中医药大学附属曙光医院,国家中医药管理局中药制剂三级实验室,上海201203

出  处:《中国药物警戒》2024年第11期1250-1255,1263,共7页Chinese Journal of Pharmacovigilance

基  金:国家自然科学基金资助项目(82104616);上海中医药大学附属曙光医院四明基金项目(SGKJ-201711)。

摘  要:目的探究鹿角方调控NF-κB信号通路对血管紧张素Ⅱ(AngⅡ)诱导的心肌细胞肥大的影响。方法以血管紧张素Ⅱ诱导建立原代乳鼠心肌细胞肥大模型,将细胞分为正常组、AngⅡ模型组、鹿角方+AngⅡ组、BAY11-7082+AngⅡ组、鹿角方+BAY11-7082+AngⅡ组。检测终浓度为0、0.1、0.3、1、3、10μg·mL^(-1)的鹿角方对心肌细胞表面积的影响;酶联免疫吸附法(ELISA)检测有效浓度10、100μg·mL^(-1)鹿角方对心肌细胞培养液中肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-2(IL-2)的含量的影响;通过实时荧光定量聚合酶链反应(q RT-PCR)检测ANP和BNP的基因表达;蛋白免疫印迹(Western Blot)法检测NF-κB p65、p-NF-κB p65(Ser536)、p-IKK(Ser176/180)、IκBα和p-IκBα(Ser32)的蛋白表达。结果与正常组相比,模型组心肌细胞表面积显著增大(P<0.01或P<0.05),肥大标志物ANP和BNP m RNA表达显著增加(P<0.01),促炎因子TNF-α、IL-1β、IL-6的水平显著升高(P<0.01),抑炎因子IL-2的水平显著降低(P<0.01),p-NF-κB p65(Ser536)、p-IKK(Ser176/180)和p-IκBα(Ser32)蛋白表达均显著增加(P<0.01),IκBα蛋白表达显著下降(P<0.01);与模型组相比,鹿角方可显著抑制心肌细胞表面积增大(P<0.01),显著抑制心肌细胞ANP和BNP m RNA表达(P<0.01),显著降低心肌细胞培养液中TNF-α、IL-1β和IL-6水平(P<0.01),显著升高IL-2的水平(P<0.01),并显著降低p-NF-κB p65(Ser536)、p-IKK(Ser176/180)和p-IKBα(Ser32)的蛋白表达(P<0.01或P<0.05),显著增加IκBα蛋白表达水平(P<0.01),且鹿角方对上述蛋白表达水平的影响与BAY11-7082相当(P>0.05)。结论鹿角方可显著抑制AngⅡ诱导的心肌细胞肥大,其机制与阻断NF-κB信号通路有关。Objective To investigate the effect of Lujiao formula on cardiac hypertrophy induced by angiotensin II(Ang II)through regulating the NF-κB signaling pathway.Methods Ang II was used to establish a cardiac hypertrophy model of neonatal rat cardiac myocytes(NRCMs).The cells were divided into normal group,AngⅡmodel group,Lujiao formula+AngⅡgroup,BAY11-7082+AngⅡgroup and Lujiao formula+BAY11-7082+AngⅡgroup.The effect of Lujiao formula with final concentrations of 0,0.1,0.3,1,3,and 10μg·mL^(-1)on the surface area of cardiomyocytes was detected.The level of tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and interleukin-2(IL-2)in culture medium of cells treated with Lujiao formula at effective concentrations of 10 and 100μg·mL^(-1)were detected by enzyme-linked immunosorbent assay(ELISA).Quantitative real-time polymerase chain reaction(RT-qPCR)was used to quantify the gene expression of ANP and BNP.Protein expression of NF-κB p65,p-NF-κB p65(Ser536),p-IKK(Ser176/180),IκBαand p-IκBα(Ser32)were detected by Western Blot.Results Compared with normal group,the surface area of cardiomyocytes in model group was significantly increased(P<0.01 or P<0.05),and the mRNA level of hypertrophy markers ANP and BNP were increased(P<0.01),and the levels of pro-inflammatory factors TNF-α,IL-1βand IL-6 were increased(P<0.01).The level of anti-inflammatory factor IL-2 was decreased(P<0.01),the protein expressions of p-NF-κBp65(Ser536),p-IKK(Ser176/180)and p-IκBα(Ser32)were significantly increased(P<0.01),and the protein expressions of IκBαwere decreased(P<0.01).Compared with the model group,Lujiao formula could significantly inhibit the increase of surface area of cardiomyocytes(P<0.01),and inhibit the expressions of ANP and BNP mRNA of cardiomyocytes(P<0.01),and reduce the levels of TNF-α,IL-1βand IL-6 in cardiomyocyte culture medium(P<0.01),and increase the level of IL-2(P<0.01).Lujiao formula could significantly decrease the protein expressions of p-NF-κB p65(Ser536),p-IKK(Ser176/18

关 键 词:鹿角方 心肌细胞 血管紧张素Ⅱ 心力衰竭 心肌细胞肥大 NF-ΚB信号通路 炎症 SD乳鼠 

分 类 号:R916.691[医药卫生—药学] R972

 

参考文献:

正在载入数据...

 

二级参考文献:

正在载入数据...

 

耦合文献:

正在载入数据...

 

引证文献:

正在载入数据...

 

二级引证文献:

正在载入数据...

 

同被引文献:

正在载入数据...

 

相关期刊文献:

正在载入数据...

相关的主题
相关的作者对象
相关的机构对象