中药材2023，Vol.46Issue(4)：986-993,8.DOI:10.13863/j.issn1001-4454.2023.04.033
基于Nrf2/HO-1信号通路探讨冠心通络方对大鼠冠脉微循环障碍的影响
Effects of Guanxin Tongluo Formula on Coronary Microcirculation Dysfunction in Rats Through Nrf2/HO-1 Pathway
摘要
Abstract
Objective:To explore the protective effect and possible mechanism of Guanxin tongluo formula on coronary microcircu-lation dysfunction(CMD)in rats through nuclear factor E2-related factor(Nrf2/HO-l)signaling pathway.Methods:Male SPF SD rats were randomly divided into sham operation group,model group,nicorandil(1.56 mg/kg)posltive control group,low,medium and high dose of Guanxin tongluo formula(8.66,17.325,34.65 g/kg)groups according to the random number table,with 10 rats in each group.Except the sham operation group,the other five groups were injected with sodium silicate(1 mg/kg)into the left ventricle to prepare CMD rat models.After successful model building,rats in Guanxin tongluo formula groups were given corresponding dose of Guanxin tongluo formula by gavage,rats in nicorandil group were given gavage of nicorandil suspension,and the other two groups were given ga-vage of the same volume of normal saline,once a day,continuous gavage for 28 days.The serum and myocardial tissue were retained af-ter echocardiography.The myocardial microthrombus formation was observed by Carstairs staining,and myocardial microinfarction was observed by Heidenhain staining.The levels of NO and ET-1 in serum and the levels of SOD,GSH-Px and MDA in myocardial tissue were determined by corresponding kit.The protein expressions of Keap 1 in myocardial tissue,Nrf2 in cytoplasm,Nrf2 and HO-1 in nu-cleus were detected by Western Blot.The protein expressions of Nrf2,Keap1 and HO-1 in myocardial tissue were detected by immuno-histochemical method.Results:Compared with the sham operation group,the heart function,serum NO level,SOD and GSH-Px levels in myocardial tissue were significantly decreased in the model group,the positive proportion of myocardial microinfarction and intra myo-cardial microthrombin was significantly increased,the serum ET-1 level and MDA level in myocardial tissue were significantly in-creased,and the expressions of Keap1 protein and cytoplasmic Nrf2 protein in myocardial tissue were significantly decreased.The ex-pressions of HO-1 and Nrf2 proteins in nucleus were significantly increased(P＜0.05 or P＜0.01).Compared with model group,the heart function of rats in the medium and high dose of Guanxin tongluo formula groups was improved,the proportion of myocardial micro-infarction,the proportion of microthrombi positive,the levels of serum ET-1 and MDA in myocardial tissue were significantly decreased,and the levels of NO in serum and SOD and GSH-Px in myocardial tissue were significantly increased in each Guanxin tongluo formula group.The expressions of Keap1 protein and Nrf2 protein in myocardial tissue were significantly decreased,while the expressions of HO-1 and Nrf2 proteins in nucleus were significantly increased(P＜0.05 or P＜0.01).Conclusion:Guanxin tongluo formula can improve the pathological process and cardiac function of CMD rats,and the mechanism may be related to the activation of Nrf2/HO-1 signaling path-way expression and the increase of antioxidant capacity.关键词
冠脉微循环障碍/核因子E2相关因子(Nrf2)/血红素加氧酶1(HO-1)信号通路/冠心通络方/氧化应激Key words
Coronary microcirculation disturbance/Nuclear factor E2 related factor(Nrf2)/heme oxygenase-1(HO-1)signaling pathway/Guanxin tongluo formula/Oxidative stress分类
医药卫生引用本文复制引用
庄园妃,钟梅,刘春贵,朱瑾娴,李雨,唐新征,蔡智刚..基于Nrf2/HO-1信号通路探讨冠心通络方对大鼠冠脉微循环障碍的影响[J].中药材,2023,46(4):986-993,8.基金项目
广东省中医药局科研项目(20181232) （20181232）
