利心冲剂对心力衰竭大鼠铁代谢SLC7A11/GXP4信号通路的调控作用  

Regulatory effect of granules for disinhibiting heart on the SALC7A11/GXP4 signaling pathway of iron metabolism in rats with heart failure

作　　者：於悦[1] 高想[1] 张锋莉[1] 盛炜[1] 卞勇[2] YU YUE;GAO Xiang;ZHANG Fengli;SHENG Wei;BIAN Yong(Nantong Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine,Nantong 226000,Jiangsu,China;Nanjing University of Chinese Medicine,Nanjing 210000,Jiangsu,China)

机构地区：[1]南京中医药大学南通附属医院,江苏南通226000 [2]南京中医药大学,江苏南京210000

出　　处：《现代中西医结合杂志》2023年第23期3230-3235,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：南通市科技局科研课题(JCZ20191,MS12021036)。

摘　　要：目的 基于心肌铁代谢探讨利心冲剂对心力衰竭大鼠的心肌保护作用。方法 取32只SD大鼠,随机选择8只SD大鼠作为正常组,其余大鼠采用腹主动脉缩窄法制备心力衰竭模型。将造模成功后大鼠随机分为模型组、利心冲剂高剂量组及利心冲剂低剂量组,每组8只。利心冲剂高、低剂量组分别予以利心冲剂20.79 g/(kg·d)和5.20 g/(kg·d)灌胃,正常组和模型组给予等量蒸馏水灌胃,均1次/d。连续灌胃8周后,比色法检测血清铁水平,ELISA法测定血清铁蛋白水平,HE染色观察心肌组织病理形态,ELISA法测定心肌组织中活性氧(ROS)水平和超氧化物歧化酶(SOD)活性,Western blot法和RT-PCR法分别检测心肌组织中转铁蛋白受体(TfR1)、膜铁转运蛋白(FPN1)、胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)蛋白及mRNA表达情况。结果 与正常组比较,模型组大鼠血清铁和铁蛋白水平、心肌组织中SOD活性和FPN1、SLC7A11、GPX4蛋白及mRNA相对表达量均明显降低(P均<0.05),心肌组织中ROS水平和TfR1蛋白及mRNA相对表达量均明显升高(P均<0.05),心肌细胞肥大,组织间可见部分炎性细胞浸润;与模型组比较,利心冲剂高剂量组血清铁和铁蛋白水平及利心冲剂高、低剂量组心肌组织中SOD活性和FPN1、SLC7A11、GPX4蛋白及mRNA相对表达量均明显升高(P均<0.05),心肌组织中ROS水平和TfR1蛋白及mRNA相对表达量均明显降低(P均<0.05),心肌损伤明显减轻。结论 利心冲剂可通过调节铁代谢SALC7A11/GXP4信号通路抑制铁死亡,减轻心肌氧化应激,缓解心力衰竭大鼠心肌损伤。Objective It is to observe the myocardial protective effect of granules for disinhibiting heart on heart failure in rats based on myocardial iron metabolism.Methods Thirty-two SD rats were taken,in which 8 rats were randomly selected as normal group,the remaining rats were used to establish models of heart failure by abdominal aortic constriction method.After successful modeling,the rats were randomly divided into model group,high dose group of granules for disinhibiting heart and low dose group of granules for disinhibiting heart,with 8 rats in each group.The high-dose and low-dose groups of granules for disinhibiting heart were respectively given granules for disinhibiting heart 20.79 g/(kg·d)and 5.20 g/(kg·d)by gavage.After 8 weeks of continuous gavage,the serum level of iron was measured by colorimetric assay,the serum level of ferritin was measured by ELISA,the pathological morphology of myocardial tissues was observed by HE staining,the level of reactive oxygen species(ROS)and activity of superoxide dismutase(SOD)in myocardial tissues were measured by ELISA,and the expressions of protein and mRNA of transferrin receptor(TfR1),membrane iron transport protein(FPN1),cystine/glutamate reverse transporter protein solute carrier family 7 member 11(SLC7A11),and glutathione peroxidase 4(GPX4)in myocardial tissues were detected by Western blot and RT-PCR,respectively.Results Compared with the normal group,the serum levels of iron and ferritin,SOD activity and relative expressions of FPN1,SLC7A11,GPX4 protein and mRNA in myocardial tissues of rats in the model group were significantly decreased(all P<0.05),the level of ROS and relative expressions of TfR1 protein and mRNA in myocardial tissues were significantly increased(all P<0.05),the cardiomyocytes were hypertrophied with some inflammatory cell infiltration.Compared with the model group,the serum levels of iron and ferritin,SOD activity of rats in the high dose group of granules for disinhibiting heart,and relative expressions of FPN1,SLC7A11,GPX4 protein and m

关 键 词：心力衰竭 铁死亡 利心冲剂 胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11 谷胱甘肽过氧化物酶4 

分 类 号：R-332[医药卫生]