Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Peng

J of Cellular Biochemistry

et al. 2019

Clinically, bone marrow mesenchymal stem cells (BMSCs) have been used in treatment of many diseases, but the local oxidative stress (OS) of lesion severely limits the survival of BMSCs, which reduces the efficacy of BMSCs transplantation. Therefore, enhancing the anti-OS stress ability of BMSCs is a key breakthrough point. Preconditioning is a common protective mechanism for cells or body. Here, the aim of this study was to investigate the effects of OS preconditioning on the anti-OS ability of BMSCs and its mechanism.Fortunately, OS preconditioning can increase the expression of superoxide dismutase, catalase, NQO1, and heme oxygenase 1 through the nuclear factor erythroid 2-related factor 2 pathway, thereby decreased the intracellular reactive oxygen species (ROS) levels, relieved the damage of ROS to mitochondria, DNA and cell membrane, enhanced the anti-OS ability of BMSCs, and promoted the survival of BMSCs under OS.

Section: Introductionmentioning

confidence: 99%

New strategy of bone marrow mesenchymal stem cells against oxidative stress injury via Nrf2 pathway: oxidative stress preconditioning

Peng

J of Cellular Biochemistry

et al. 2019

“…As mentioned above, apoptosis and inflammation are important mechanisms associated with II/R injury. TUNEL staining is one major method to detect cell apoptosis, and pro‐inflammatory factors including IL‐1β, IL‐6, and TNF‐α can reflect inflammatory response (Y. Li, Wen, et al, ; Y. Li, Xu, et al, ; Zu, Zhou, Che, & Zhang, ). In this study, our results showed that the numbers of apoptotic cells and the mRNA levels of IL‐1β, IL‐6, and TNF‐α were significantly increased after 4 hr of hypoxia and 120 min of reoxygenation in IEC‐6 cells and ischaemia for 45 min and reperfusion for 90 min in mice compared with control group or sham group, which were reduced with the prolongation of reoxygenation or reperfusion time compared with 120 min of reoxygenation in vitro or reperfusion for 90 min in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the data in Li, Wen, et al, 2017;Y. Li, Xu, et al, 2017;Zu, Zhou, Che, & Zhang, 2018). In this study, our results showed that the numbers of apoptotic cells and the mRNA levels of IL-1β, IL-6, and TNF-α were significantly increased after 4 hr of hypoxia and 120 min of reoxygenation in IEC-6 cells and ischaemia for 45 min and reperfusion for 90 min in mice compared with control group or sham group, which were reduced with the prolongation of reoxygenation or reperfusion time compared with 120 min of reoxygenation in vitro or reperfusion for 90 min in vivo.…”

Section: Overexpression Of Mir-29b-3p Alleviated H/r-caused Injury mentioning

confidence: 98%

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Han

et al. 2019

British J Pharmacology

Background and Purpose The microRNA miR‐29b‐3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR‐29b‐3p on II/R injury on order to find drug targets to treat the injury. Experimental Approach Two models ‐ in vitro hypoxia/reoxygenation (H/R) of IEC‐6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual‐luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR‐29b‐3p on II/R injury via targeting TNF receptor‐associated factor 3 (TRAF3). Key Results The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC‐6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR‐29b‐3p were decreased in H/R‐induced cells and II/R‐induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR‐29b‐3p level markedly increased TRAF3 expression via activating TGF‐α‐activated kinase 1 phosphorylation, increasing NF‐κB (p65) levels to promote inflammation, up‐regulating Bcl2‐associated X expression, and down‐regulating Bcl‐2 expression to trigger apoptosis. In addition, the miR‐29b‐3p mimetic and TRAF3 siRNA in IEC‐6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. Conclusions and Implications The miR‐29b‐3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.

“…Hence, lPS-induced lung injury is always used to study gram-negative bacterial-associated lung injury (54). The protective mechanisms of deX on lung injury induced by iir or lPS may not exactly be the same, since the activation of the nrf2/Ho-1 pathway has been reported to decrease oxidation products and improve intestinal mucosal injury in an iir model (55). Ho-1 is also a stress-responsive enzyme that produces antioxidants and anti-inflammatory agents (56).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with dexmedetomidine alleviates lung injury in a rat model of intestinal ischemia reperfusion

Chen

Bian

2020

Mol Med Report

The aim of the present study was to investigate the antioxidant mechanisms of dexmedetomidine against lung injury during intestinal ischemia reperfusion (iir) in rats. The model of iir-induced acute lung injury was established by occluding the superior mesenteric artery (SMa) for 1 h and reperfusing for 2 h using Sprague-dawley rats. Pathological examination was used to assess the extent of the lung injury. oxidative stress was evaluated by measuring malondialdehyde, myeloperoxidase and superoxide dismutase in the lung and plasma. The proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were determined via an enzyme-linked immunosorbent assay. The mrna and protein expression of nuclear factor-erythroid 2 related factor 2 (nrf2) and heme oxygenase 1 (Ho-1) were determined using a reverse transcription-quantitative polymerase chain reaction and western blotting. Pretreatment with dexmedetomidine significantly inhibited the oxidative stress response and proinflammatory factor release caused by IIR compared with the normal saline group (Mda and Sod in lung and plasma, P<0.05; MPo, il-1β and TnF-α in lung and plasma, P<0.05). dexmedetomidine improved pulmonary pathological changes in iir rats compared with the normal saline group. investigations into the molecular mechanism revealed that dexmedetomidine increased the expression levels of nrf2 and Ho-1 via activating α2 adrenergic receptors compared with the normal saline group. The antagonism of α2 adrenergic receptors may reverse the protective effect of dexmedetomidine on lung injury during iir, including decreasing the expression levels of nrf2 and Ho-1, elevating the oxidative stress response and increasing the proinflammatory factor release. in conclusion, pretreatment with dexmedetomidine demonstrated protective effects against lung injury during iir via α2 adrenergic receptors. The nrf2/Ho-1 signaling pathway may serve a function in the protective effect of dexmedetomidine.