Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression

Yang, Xin-lu; Shu, Shuhua; Wang, Sheng; Guo, Fenglin; Yin, Ying; Zhou, Wuhua; Han, Han; Chai, Xiangping

doi:10.1007/s10753-020-01410-x

Cited by 18 publications

(12 citation statements)

References 38 publications

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“…also found that it inhibits inflammatory damage during liver ischemiareperfusion. 8 , 9 Our results also found that the expression of a large number of inflammatory cytokines in the MCAO model rats was significantly increased, which indicated that the inflammatory response was involved in the brain injury of the MCAO model rats. The inflammatory cytokines of SUF pretreated rats were significantly downregulated, indicating that SUF effectively alleviated the brain injury of MCAO rats by inhibiting inflammation.…”

Section: Discussionsupporting

confidence: 65%

“… 7 In recent years, some clinical and animal experimental studies have found that SUF has a good protective effect against ischemia-reperfusion injury. 8 , 9 SUF can protect the liver from ischemia-reperfusion injury by its excellent anti-inflammatory effect. 8 In addition, SUF has also been found to alleviate myocardial ischemia-reperfusion injury by activating the ERK1/2 signaling pathway or miR-125a/DRAM2 axis.…”

Section: Introductionmentioning

confidence: 99%

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Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

Wang

et al. 2022

Eur J Histochem

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Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

Wang

et al. 2022

Eur J Histochem

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“…Rats in the control group underwent thoracotomy without ligation. Rats in the SUF group were intravenously injected with 3 μ g/kg sufentanil (Yichang Humanwell Pharmaceutical Co., Ltd., China) at 30 min before surgery [ 18 ]. Rats in the DLZ group were intravenously injected with 20 mg/kg diltiazem (Hunan Zhongdama Pharmaceutical Technology Co., Ltd., China) 30 min prior to I/R.…”

Section: Methodsmentioning

confidence: 99%

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

Qiu

Zhong

Hou

et al. 2022

Computational and Mathematical Methods in Medicine

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Objective. Sufentanil is the most common drug in clinical practice for the treatment of ischemic heart disease. This study is to investigate the protective mechanism of sufentanil on rat myocardial ischemia-reperfusion (I/R) injury. Methods. A rat I/R model was established by ligating the left anterior descending coronary artery. A total of 24 SD male rats were enrolled and divided randomly into the control group, I/R group, sufentanil group (SUF; 3 μg/kg), and diltiazem group (DLZ; 20 mg/kg; positive control). The rat hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion. Subsequently, hemodynamics, pathological changes of myocardial tissue, serum biochemical parameters, oxidative stress factors, the level of serum inducible nitric oxide synthases (iNOS), interleukin-6 (IL-6), and other bioactive factors were analyzed in the rats. Result. Compared with the I/R group, sufentanil significantly improved cardiac action, myocardial fiber, and cardiomyocyte morphology and reduced inflammatory cell infiltration in rats in the SUF group. And the level of creatine kinase isoenzyme (CK-MB), troponin (cTn), lactate dehydrogenase (LDH), malondialdehyde (MDA), iNOS, and IL-6 was significantly declined in the serum of SUF group, while the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly activated in the myocardial tissues. In addition, sufentanil also significantly decreased the protein expression of GRP78, CHOP, Caspase 12, and ATF6 in the myocardial tissue of the SUF group. Conclusion. Sufentanil has a significant protective activity on myocardial I/R injury in rats, the mechanism of which may be associated with the inhibition of endoplasmic reticulum stress and oxidative stress.

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“…BRL-3A cells in the logarithmic phase were harvested for follow-up experimental study. Experiments to induce H/R cell model was carried out as mentioned in previous study [ 13 ]. In briefly, the collected cells were cultivated in serum-free DMEM medium and maintained in a 5% CO 2 , and 95% N 2 hypoxia incubator at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Nuclear receptor 4A1 (NR4A1) silencing protects hepatocyte against hypoxia-reperfusion injury in vitro by activating liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling

Zheng

Tao²,

Zhan

et al. 2022

Bioengineered

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The nuclear receptor 4A1 (NR4A1) is widely involved in the regulation of cell survival and is related to ischemic injury in several organs. This research examined the emerging role and mechanism of NR4A1 in hepatocyte ischemia-reperfusion injury (IRI). BRL-3A cells were subjected to hypoxia-reperfusion (H/R) to simulate an IRI model in vitro . The expression of NR4A1 and liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) pathway-related proteins (LKB1, AMPK, and ACC) was detected by western blotting or RT-qPCR under H/R condition after NR4A1 overexpression or silencing. Then, radicicol, an inhibitor of LKB1 pathway, was used to determine the role of NR4A1 in hepatocyte H/R injury by regulating LKB1. Under the help of CCK-8 assay, cell viability was assessed. The levels of ROS, MDA, and SOD were determined with corresponding kits to evaluate oxidative stress. Additionally, RT-qPCR was employed to analyze the releases of the inflammatory factors. Flow cytometry was applied to estimate the apoptosis and its related proteins, and autophagy-associated proteins were assayed by western blotting. Results indicated that NR4A1 was highly expressed, while proteins in LKB1/AMPK signaling was downregulated in BRL-3A cells exposed to H/R. The activation of LKB1/AMPK pathway could be negatively regulated by NR4A1. Moreover, NR4A1 depletion conspicuously promoted cell viability, inhibited oxidative stress as well as inflammation, and induced apoptosis and autophagy in H/R-stimulated BRL-3A cells, which were reversed after radicicol intervention. Collectively, NR4A1/LKB1/AMPK axis is a new protective pathway involved in hepatocyte IRI, shedding new insights into the improvement of hepatocyte IRI.

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Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression

Cited by 18 publications

References 38 publications

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

Sufentanil alleviates cerebral ischemia-reperfusion injury by inhibiting inflammation and protecting the blood-brain barrier in rats

Protective Effect of Sufentanil on Myocardial Ischemia-Reperfusion Injury in Rats by Inhibiting Endoplasmic Reticulum Stress

Nuclear receptor 4A1 (NR4A1) silencing protects hepatocyte against hypoxia-reperfusion injury in vitro by activating liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) signaling

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