TNF-α inhibitor protects against myocardial ischemia/reperfusion injury via Notch1-mediated suppression of oxidative/nitrative stress

2015 ◽  
Vol 82 ◽  
pp. 114-121 ◽  
Author(s):  
Haifeng Pei ◽  
Xiaofeng Song ◽  
Chengfei Peng ◽  
Yan Tan ◽  
Ying Li ◽  
...  
2020 ◽  
Author(s):  
Xingye Wang ◽  
Zhenzhu Hao ◽  
Xinghu Piao ◽  
Li Sun ◽  
Ye Tao ◽  
...  

Abstract Background: The traditional Chinese medicine Shuxin Shengmai Dan (SXSMD) is clinically used to treat angina pectoris. The mechanism of action of SXSMD protection of the heart involves inhibition of inflammation and remains poorly understood. The role of SXSMD in rats with myocardial ischemia reperfusion (IR) and the mechanism of SXSMD action were studied in this research.Methods: The rats were treated with SXSMD (3.38, 6.76, and 13.52 g/kg/day, p.o.) or Danshen injecta (1.8 mL/kg/day, p.o.) for 15 days, then the coronary arteries were ligated. Cardiac function was evaluated by electrocardiography and hemodynamic measurements. Hematoxylin-eosin (H&E) staining was used to detect pathological changes in ischemic myocardial sections. Transmission electron microscopy (TEM) was used to assess the ultrastructure of cardiomyocytes. The changes in IL-6 and TNF-α in the rat serum were detected by ELISA. The changes in the expression levels of HMGB1, TLR4, MyD88, and NF-κB mRNAs and proteins related to the TLR4/NF-κB pathway in myocardial tissue were detected by qPCR and Western blot, respectively.Results: Rats with coronary artery ligation had abnormal cardiac function, inflammatory infiltration of myocardial cells, disordered myocardial fiber arrangement, accumulation of mitochondria, and disordered muscle fibers and sarcomeres according to electron microscopy. The levels of the expression of mRNAs and proteins in myocardial tissue of the SXSMD group were decreased compared with those in the MIRI group. The serum levels of IL-6 and TNF-α were decreased. SXSMD treatment can inhibit the inflammatory response and downregulate the TLR4/NF-κB pathway in cardiomyocytes.Conclusion: SXSMD protects the rats from myocardial ischemia-reperfusion injury in the MIRI model by downregulating the TLR4/NF-κB pathway to inhibit inflammation.


2019 ◽  
Author(s):  
Jianfeng Chen ◽  
Shufeng Xue ◽  
Mingming Zhang ◽  
Junlong Wu ◽  
Shouyan Zhang

Abstract Background This study aimed to investigate the effect of miR-30c on myocardial ischemia reperfusion (IR) injury and its underlying molecular mechanisms.Methods In our study, rat myocardial IR injury model was established and hemodynamic examination was performed. Moreover, the myocardial infarct size was detected by TTC staining. The pathologic change of myocardial tissues was measured by HE staining. The myocardial cell apoptosis was measured by TUNEL staining and flow cytometry. The expression of miR-30c and Sirtuin 1 (SIRT1) was detected by qRT-PCR. The levels of IL-1β, IL-6 and TNF-α were detected by ELISA. The expressions of Bax, Bcl-2, caspase-3, p-IκBα, IκBα, p-NF-κB p65, NF-κB p65 and SIRT1 were detected by western blot. The luciferase activity was measured by dual luciferase reporter gene assay. Interaction between miR-30c and SIRT1 were analyzed by RNA immunoprecipitation assay.Results Our results showed that rat myocardial IR injury model was successfully established and IR injury induced myocardial injury in rats. miR-30c increased the levels of IL-1β, IL-6 and TNF-α and myocardial cell apoptosis by activating NF-κB pathway. In addition, we also confirmed that SIRT1 was the target gene of miR-30c. SIRT1 could reverse the effect of miR-30c on the process of inflammation and apoptosis, as well as the activation of NF-κB pathway in myocardial cells.Conclusions Our study demonstrated that miR-30c could promote myocardial ischemia reperfusion injury through activating SIRT1 mediating NF-κB pathway.


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