Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway

Zhang, Minghao; Wang, Xiuyu; Bai, Bin; Zhang, Rui; Li, Yunhong; Wang, Yin

doi:10.3892/mmr.2016.5250

Cited by 36 publications

(33 citation statements)

References 24 publications

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“…34,35 The present study investigated lncRNA CRNDE as a potential modulator of inflammatory responses underlying sepsis pathogenesis. Specifically, the clinical analyses demonstrated that CRNDE was differentially expressed within sepsis patients of distinct prognosis (Figure 1c), and in vitro tests also uncovered that CRNDE could propel expression of sepsis-specific biomarkers, including TNF-a, 36 IL-1b, 37 NF-kB 38 and IL-6 34 (Figure 2). CRNDE had been previously reported as a modulator of sepsis-initiated inflammatory pathways as mentioned above.…”

Section: Discussionmentioning

confidence: 98%

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

Wang

Yue

et al. 2019

Innate Immun

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This investigation was performed to verify whether lncRNA CRNDE sponging miR-181a-5p was involved with sepsisrelevant inflammatory dysfunctions. Aggregately 136 sepsis patients and 151 healthy people were recruited, and their fasting peripheral blood was gathered to detect expressions of CRNDE and miR-181a-5p. In addition, THP-1 cells were transfected with si-CRNDE, miR-181a-5p mimic, pcDNA3.1-TLR4 and si-TLR4, and then sepsis-specific inflammatory cytokines within the cells were quantified. The sponging relationships between CRNDE and miR-181a-5p, as well as between miR-181a-5p and TLR4, were ascertained by means of luciferase reporter gene assay. The experimental results revealed that over-expressed CRNDE and under-expressed miR-181a-5p were associated with shortened lifespan of sepsis patients. Mechanically, si-CRNDE-1 and miR-181a-5p mimic were able to reverse the promoting effects of LPS on production of NF-kB, TNF-a, IL-1b and IL-6 by THP-1 cells. Moreover, the expressional change of miR-181a-5p in THP-1 cells was in part owing to its being sponged by CRNDE. Lastly, TLR4, subjected to targeted modification of miR-181a-5p, was capable of disturbing the contribution of CRNDE and miR-181a-5p to THP-1 cells' release of NF-kB, TNF-a, IL-1b and IL-6. Collectively, the CRNDE/miR-181a-5p/TLR4 axis seemed to have potential in modifying sepsisrelated inflammatory pathogenesis, which offered a direction for sepsis diagnosis and treatment.

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Section: Discussionmentioning

confidence: 98%

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

Wang

Yue

et al. 2019

Innate Immun

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“…In line with our finding, previously, AT1R was demonstrated to induce extracellular signal-regulated kinases (ERK1/2) and p38 MAPK. 3 Another study noted that declined proinflammatory cytokines and inactivation of the p38 MAPK signaling pathway caused by irbesartan could contribute to attenuated cardiac dysfunction during sepsis. 39 Furthermore, activation of the AT1R/p38 MAPK signaling pathway was associated with myocardial injury in myocardial infarction-induced rat models, indicating that AT1R silencing and inactivation of the MAPK signaling pathway may contribute to reducing myocardial injury.…”

Section: Discussionmentioning

confidence: 99%

Retracted: AT1R knockdown confers cardioprotection against sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway in rats

Zhang

Yin

et al. 2018

J of Cellular Biochemistry

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Myocardial dysfunction is an important manifestation of sepsis. In addition, inactivation of the mitogen‐activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in sepsis. The current study used gene expression profiling to demonstrate the overexpression of angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in sepsis. In this study, we used a rat model of sepsis established by cecal ligation and puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed. Enzyme‐linked immunosorbent assay was used to measure the concentration of cardiac troponin T (TnT), cardiac troponin I (cTnI), and creatine kinase isoenzyme muscle/brain (CK‐MB). Myocardial enzyme, tissue antioxidant capacity, mitochondria swelling, and membrane potential were also detected. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and protein levels of apoptosis‐related proteins (Fas ligand [Fasl], B‐cell CLL/lymphoma [Bcl‐2], p53) were also detected. Initially, sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of TnT, cTnI, and CK‐MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased extracellular signal–regulated kinase and cyclic adenosine 3′,5′‐monophosphate response element binding protein expression), decreased EF, heart rate, and concentrations of TnT, cTnI, and CK‐MB, but increased sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl‐2 expression). These findings indicated that AT1R silencing plays an inhibitory role in sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway.

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“…3A). Previous studies have reported that sepsis-induced cardiac dysfunction was positively correlated with myocardial apoptosis (26,27). Thus, the TUNEL assay was used to examine the rate of myocardial apoptosis in the experimental groups.…”

Section: Apelin Treatment Improves Survival and Attenuates Clp Sepsismentioning

confidence: 99%

Apelin protects against sepsis‑induced cardiomyopathy by inhibiting the TLR4 and NLRP3 signaling pathways

et al. 2018

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The mechanism underlying sepsis‑induced cardiomyopathy (SICM) remains unclear. The aim of the present study was therefore to illuminate the mechanisms and effects of apelin on SICM, using both patient clinical features and a sepsis rat model. A total of 73 adult patients with or without sepsis were analyzed. Male rats were used to generate the sepsis model through cecal ligation and puncture (CLP). The clinical analysis results demonstrated that sepsis induced cardiac dysfunction, including a decrease of left ventricular end‑diastolic dimension, fractional shortening, ejection fraction, left ventricular end‑systolic dimension, and stroke volume, compared with healthy controls. In addition, the results demonstrated that white blood cell count and inflammatory cytokine expression increased in sepsis patients compared with healthy controls. ELISA analyses revealed that apelin was upregulated following sepsis. The animal model study demonstrated that rats treated with apelin had significantly reduced mortality and suppressed sepsis‑induced myocardial damage and inflammatory responses, through suppression of activation of the Toll‑like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3) signaling pathways. Taken together, the present results suggested that apelin had a protective effect against sepsis‑induced cardiac impairment by attenuating TLR4 and NLRP3 signaling‑mediated inflammatory responses.

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Oxymatrine protects against sepsis-induced myocardial injury via inhibition of the TNF-α/p38-MAPK/caspase-3 signaling pathway

Cited by 36 publications

References 24 publications

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

Linkage of lncRNA CRNDE sponging miR-181a-5p with aggravated inflammation underlying sepsis

Retracted: AT1R knockdown confers cardioprotection against sepsis‐induced myocardial injury by inhibiting the MAPK signaling pathway in rats

Apelin protects against sepsis‑induced cardiomyopathy by inhibiting the TLR4 and NLRP3 signaling pathways

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