摘要
目的评估豨加精方对环磷酰胺致小鼠心脏毒性的保护作用,并探讨其作用机制。方法将60只ICR雄性小鼠随机分为空白组、模型组和豨加精方低、中、高剂量组(5.525、11.05、22.10g/kg)。豨加精方3个剂量组均预防性灌胃给药7d,每天1次,第7天给予模型组与豨加精方各剂量组小鼠腹腔注射环磷酰胺200mg/kg。末次给药后超声监测各组小鼠心功能;ELISA法测定小鼠血清和心脏组织中心肌损伤标志物肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白T(cTnT),氧化应激和铁死亡指标过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)的含量;Western blot检测小鼠心脏组织中调控铁死亡的信号分子酪氨酸蛋白激酶(Fyn)和环氧化酶-2(COX2)蛋白表达水平。结果与空白组比较,模型组小鼠室壁振幅减低,左室射血分数(LVEF)、左室短轴缩短率(LVFS)显著降低(P<0.05);血清中CK-MB、LDH、cTnT、CAT、MDA含量显著升高(P<0.05),SOD、GSH含量显著降低(P<0.05);心脏组织中MDA含量显著升高(P<0.05),GSH含量显著降低(P<0.05);Fyn和COX2的蛋白表达水平明显上升(P<0.05)。与模型组比较,豨加精方高剂量组小鼠的LVEF和LVFS显著升高(P<0.05);豨加精方低、中、高3个剂量组小鼠血清中CK-MB、LDH、cTnT、CAT、MDA水平均显著降低(P<0.05),SOD、GSH水平显著升高(P<0.05);豨加精方高剂量组小鼠心脏组织中MDA水平显著降低(P<0.05),GSH水平显著升高(P<0.05),Fyn、COX2蛋白水平显著降低(P<0.05)。结论豨加精方能明显减轻环磷酰胺引起的小鼠心肌损伤,其作用可能与调控Fyn-COX2,抑制氧化应激和铁死亡途径有关。
Objective To evaluate the protective effect of Xijiajing formula on cyclophosphamide-induced cardiotoxicity in mice and to explore its mechanism of action.Methods Sixty ICR male mice were randomly divided into Control group,Model group,Xijiajing formula low,medium,high doses(5.525,11.05,22.10 g/kg)groups.Three dose groups of Xijiajing were given prophylactic medication orally for 7 days,once a day.On the 7th day,mice in the Model group and Xijiajing intervention groups were intraperitoneally injected with cyclophosphamide 200 mg/kg.The cardiac function in each group of mice was monitored by ultrasound after the last administration of drugs.ELISA was performed to determine the levels of myocardial injury markers CK-MB,LDH,and cTnT,as well as the indicators of oxidative stress and ferroptosis markers CAT,SOD,MDA,and GSH in serum and cardiac tissues of mice.Western blot was used to detect the protein expression levels of tyrosine protein kinase(Fyn)and cyclooxygenase-2(COX2),signaling molecules that regulate iron death,in mouse heart tissues.Results Compared with the Control group,the Model group had reduced ventricular wall amplitude,significantly lower LVEF and LVFS(P<0.05).Serum levels of CK-MB,LDH,cTnT,CAT,and MDA were significantly higher(P<0.05),while SOD and GSH levels were significantly lower(P<0.05)in Model group.Cardiac tissues levels of MDA was significantly higher(P<0.05),and GSH was significantly lower(P<0.05)in Model group.Protein expression levels of Fyn and COX2 were significantly higher(P<0.05)in Model group.Compared with the Model group,the LVEF and LVFS of mice in the Xijiajing formula high doses group were significantly higher(P<0.05).The serum levels of CK-MB,LDH,cTnT,CAT,and MDA were significantly decreased(P<0.05),while the levels of SOD and GSH were significantly increased(P<0.05)in mice of Xijiajing low,medium,and high dose groups.MDA levels were significantly reduced(P<0.05)and GSH levels were significantly increased(P<0.05),while Fyn and COX2 protein levels decreased(P<0.05)in the heart tissues of mice in the Xijiajing formula high dose group.Conclusion Xijiajing formula significantly attenuated cyclophosphamide-induced myocardial injury in mice,and its effects may be related to the modulation of Fyn-COX2,inhibition of oxidative stress and ferroptosis pathway.
作者
彭梦琪
卫晓红
林宏远
张晓维
商洪才
PENG Mengqi;WEI Xiaohong;LIN Hongyuan;ZHANG Xiaowei;SHANG Hongcai(Shandong Second Medical University,Weifang 261053,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410005,China;School of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中国中医基础医学杂志》
2025年第4期627-631,共5页
JOURNAL OF BASIC CHINESE MEDICINE
基金
国家科技重大专项(2023ZD0502700,2023ZD0502705)
北京市通州区2023年度医药健康产业发展项目(JX2023YJ024)。
关键词
豨加精方
环磷酰胺
心脏毒性
铁死亡
Xijiajing formula
Cyclophosphamide
Cardiotoxicity
Ferroptosis
