Objective To evaluate the effects of dexmedetomidine on oxidative stress response and apoptosis during lung ischemia-reperfusion (IR) in rats. Methods Forty-eight adult male Sprague-Dawley rats were randomly divided into 3 groups (n=16 each) using a random number table: sham operation group (group S), group IR, and dexmedetomidine pretreatment+IR group(group D).Dex medetomidine was injected at 25 μg·kg-1 20 min before ischemia in Dex group.The equal volume of 0.9% sodium chloride soution was injected into group S and group IR, respectively.Rats were euthanized 2 h after reperfusion.The left lung tissue was extracted.Wet lung weight and dry lung weight (W/D) and total lung water content (TLW) were tested.Morphology of lung tissue was observed.The left lung tissues were removed for determination of malondialdehyde (MDA) content (by thiobarbituric acid method) and superoxide dismutase (SOD) activity (using xan-thine oxidase method).The bcl-2, bax and Caspase-3 protein expression was detected by Western blotting. Results Compared with group S, W/D and TLW of the lung tissue in the other two groups were all significantly increased (P<0.01).Compared with group IR, W/D and TLW of the lung tissues in group D were all significantly reduced (P<0.01).As compared with group S, MDA was increased and SOD decreased, bax and Caspase-3 protein expression increased, bcl-2 protein expression decreased in the lung tissue of the other two groups (P<0.01).As compared with group IR, MDA decreased and SOD increased more significantly in group D (P<0.01), bax and Caspase-3 protein expression decreased and bcl-2 increased more significantly (P<0.01). Conclusion Dexmedetomidine can alleviate lung IR injury in rats, and the mechanism is related to inhibition of oxidative stress response and apoptosis.
DENGC,ZHAIZ,WUD,et al.Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in all experimental pulmonary thromboembolism model[J].Thromb Thrombolysis,2015,40(1):42-53.
Lung ischemia–reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. The inflammatory response mechanisms related to LIRI in pulmonary thromboembolism...
KONISHIT.Brain oxidative stress as basic target of antioxidant traditional oriental medicines[J].Neurochem Res,2009,34(4):711-715.
Prevention and amelioration of Mibyou (sub-healthy condition) is the critical target for disease prevention including age-related diseases and cancer although the Mibyou condition is not yet pathologically defined. Since the oxidative stress is an underlying basic etiology associated with many diseases and aging, the psychologically induced oxidative stress, especially in the brain was supposed as one of the pathology of Mibyou. Several traditional herbal prescriptions applied for the brain disorder were found effective to prevent cerebral oxidative stress induced by ischemia/reperfusion and also under psychological distress produced by whiskers cut in mice. Shengmai San comprising three herbs, Panax ginseng , Ophiopogon japonicus and Schisandra chinensis is a traditional herbal medicine formula having a long history of using as a remedy and clinical prescription to treat coronal heart diseases. Multifunctional aspect of traditional herbal prescription was discussed in terms of preventing oxidative injury in the brain using Shengmai San as a typical prescription.
EPPINGER MJ,JONES ML,DEEBM,et al.Pattern of injury and the role of neutrophil in reperfusion injury in the rat lung[J].Surg Res,1995,58(6):276-280.
Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P lt 0. 0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P lt 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia ( lt 75/mm-3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P lt 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events.
JIANGL,LIL,SHENJ,et al.Effecl of dexmedetomidine on lung ischemia-reperfusion injuryI[J].Mol Med Rep,2014,9(2):419-426.
Dexmedetomidine, a specific selective (2)-adrenergic agonist, does not only have the characteristics of being a sedative and analgesic, but also exhibits a protective role in brain ischemia-reperfusion injury and inhibits the inflammation in animals with sepsis. The objective of the present study was to investigate whether dexmedetomidine is capable of attenuating rat pulmonary damage induced by ischemia-reperfusion injury, which is a type of acute sterile lung injury. Sprague-Dawley rats were randomly assigned into six groups: The sham-operated (sham) group, the lung ischemia-reperfusion (I/R) group, intravenous injection of dexmedetomidine 2.5 g/kg/h (Dex2.5) or 5 g/kg/h (Dex5) for 1 h prior to ischemia, combination of (2)-adrenergic antagonist yohimbine prior to dexmedetomidine pre-treatment (Dex+Yoh) and pre-administration of yohimbine alone (Yoh) prior to ischemia. Lung injury was assessed by the histopathological changes, arterial blood gas, wet/dry (w/d) weight ratio and myeloperoxidase (MPO) activity of the lung. The concentration of tumor necrosis factor- (TNF-), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF) was measured by an enzyme-linked immunosorbent assay. The expression of toll-like receptor-4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA in the lung were determined by quantitative PCR, and phosphorylated levels of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 were determined by western blotting. Pre-treatment with dexmedetomidine significantly reduced the lung injury, w/d weight ratio and MPO activity, and decreased the concentration of TNF-, IL-6 and MCP-1 in BALF compared with the I/R group. The expression of TLR4 and MyD88 mRNA and the levels of phosphorylated JNK and ERK1/2 in the lung tissue were markedly downregulated by intravenous injection of dexmedetomidne for 1 h prior to lung I/R. The protective effects of dexmedetomidine on the lung were not completely reversed by the (2)-adrenergic antagonist, yohimbine. Pre-treatment with dexmedetomidine is capable of reducing pulmonary damage and inhibiting sterile inflammation induced by lung I/R injury. TLR4/MyD88/mitogen-activated protein kinase (MAPK) signaling is involved in the protective mechanism of dexmedetomidine through (2)-adrenoceptor independence.
CAIY,XUH,YANJ,et al.Molecular targets and mechanism of dexmedetomidine in treatment of ischemia/reperfusion iniury[J].Mol Med Rep,2014,9(5):1542-1550.
Dexmedetomidine (DEX), a highly specific α262adrenergic agonist, which exhibits anaesthetic62sparing, analgesia and sympatholytic properties. DEX modulates gene expression, channel activation, transmitter release, inflammatory processes and apoptotic and necrotic cell death. It has also been demonstrated to have protective effects in a variety of animal models of ischemia/reperfusion (I/R) injury, including the intestine, myocardial, renal, lung, cerebral and liver. The broad spectrum of biological activities associated with DEX continues to expand, and its diverse effects suggest that it may offer a novel therapeutic approach for the treatment of human diseases with I/R involvement.
GUJ,CHENJ,XIAP,et al.Dexmedetomidine attenuates remote lung injury induced by renal ischemia-reperfusion in mice[J].Acta aesthesiol Scand,2011,55(10):1272-1278.
BackgroundRenal ischemia–reperfusion (I/R) may cause acute lung injury (ALI). The mortality of combined acute kidney injury and ALI is extremely high. Dexmedetomidine, an α2 adrenergic agonist, exerts potent anti-inflammatory and organoprotective effects in addition to its sedative and analgesic properties. We sought to elucidate whether dexmedetomidine can attenuate lung injury following renal I/R in a murine model of renal I/R.MethodsAdult C57BL/6J male mice were randomized to five groups: sham-operated control (Sham); renal I/R (I/R); intraperitoneal injection of dexmedetomidine 2565μg/kg before ischemia (pre-dex) and after perfusion (post-dex); combination of α2 adrenergic antagonist atipamezole 25065μg/kg prior to dexmedetomidine pre-treatment (atip-dex). Kidney I/R was induced by bilateral renal pedicle clamping for 4565min and followed by 665h reperfusion. The pulmonary tissues were harvested for histopathological evaluation, wet/dry ratio measurement, biochemical analysis of myeloperoxidase (MPO), Polymerase chain reaction (PCR) determination of Inter-cellular adhesion molecule (ICAM-1) and Tumor necrosis factor – alpha (TNF-α) mRNA.ResultsRenal IR induced significant pulmonary injuries, increased wet/dry ratio together with the enhanced of MPO activities and increased ICAM-1 and TNF-α mRNA level. Both pre- and post-treatment with dexmedetomidine markedly reduced lung edema and inflammatory response and lowered MPO activity and ICAM-1 and TNF-α mRNA expression. The protective effects of dexmedetomidine in the lung were partially reversed by atipamezole, but there were no effect on ICAM-1 and TNF-α mRNA expression level.ConclusionsDexmedetomidine is capable of attenuating remote lung injury induced by renal IRvia both α2 adrenoceptors dependent and independent mechanisms.
HEF,XU BL,CHENC,et al.Methylophiopogonanone A sup-presses ischemia/reperfusion-induced myocardial apoptosis in mice via activating P13K/Akt/eNOS signaling pathway[J].Acta Pharmacol Sin,2016,37(6):763-771.
The dried tuber root ofOphiopogon japonicushas been used in the traditional Chinese medicine for treatment of myocardial ischemia and thrombosis. In this study we investigated the effects of methylophiopogonanone A (MO-A), a major homoisoflavonoid inOphiopogon japonicus, on myocardial ischemia/reperfusion (I/R) injury. Mice were pretreated with MO-A (10 mgd-1,po) for 2 weeks and then subjected to transient occlusion of the left anterior descending coronary artery. Cardiac function was evaluated, and the infarct size and apoptosis index were assessed. The mechanisms underlying the cardio-protection of MO-A were analyzed in H9C2 rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R). The cell viability and apoptosis were evaluated; apoptotic and relevant signaling proteins were analyzed. NO levels in the culture medium were assessed. In I/R mice, pretreatment with MO-A significantly reduced the infarct size (by 60.7%) and myocardial apoptosis (by 56.8%), and improved cardiac function. In H9C2 cells subjected to H/R, pretreatment with MO-A (10 ol/L) significantly decreased apoptosis and cleaved caspase-3 expression, elevated the Bcl-2/Bax ratio and restored NO production. Furthermore, pretreatment with MO-A markedly increased the activation of PI3K/Akt/eNOS pathway in H9C2 cells subjected to H/R, and the protective effects of MO-A were abolished in the presence of the PI3K inhibitor wortmannin (100 nmol/L). MO-A attenuates I/R-induced myocardial apoptosis in mice via activating the PI3K/Akt/eNOS signaling pathway.
FANGJ,HUF,KED,et al.N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through P13K/Akt pathway in mice[J].Basic Res Cardiol,2016,111(3):32-34.
N, N-dimethylsphingosine (DMS) has been documented to be in vitro protective against myocardial ischemia–reperfusion injury (IRI) and can recruit CD4+CD25+Foxp3+regulatory T cells (Tregs), which may...
STOOPS WW,HATTON KW,LOFWALL MR,et al.Intravenous oxycodone,hydreeodone,and morphine in recreational opioid users:abuse potential and relative potencies[J].Psychopharmacology(Bed),2010,212(2):193-203.
Rationale Nonmedical use and abuse of prescription opioids is an increasing public health problem. Intravenous (IV) administration of opioid analgesics intended for oral use is not uncommon; yet, little is known about the relative abuse potential of these drugs when administered intravenously to recreational opioid abusers without physical dependence. Methods This inpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential of IV doses of oxycodone, hydrocodone, and morphine. Nine healthy adult participants reporting recreational opioid use and histories of IV opioid use completed 11 experimental sessions, including one active-dose practice session. IV doses were infused over 5min and included three identical doses of each opioid (5, 10, and 20mg/10ml) and saline placebo. Physiological, subjective, and performance effects were collected before and for 6h after drug administration. Results All three opioids produced prototypical mu agonist effects (e.g., miosis; increased ratings of liking) that were generally dose-related. Pharmacodynamic effects were observed within 5min of IV administration. Physiological effects were more prolonged than subjective effects for all three drugs. While the magnitude of effects was generally comparable across drugs and qualitatively similar, valid potency assays indicated the following potency relationship: oxycodone > morphine > hydrocodone. Conclusions There were modest potency differences between oxycodone, hydrocodone, and morphine, but their overall profile of effects was similar, indicating significant abuse potential when administered intravenously.
HATCHER HC,TESFAYL,TORTI SV,et al.Cytoproteetive effect of ferritinh in renal isehemia reperfusion injury[J].PLoS One,2015,10(9):138-140.
[本文引用:1]
[15]
AHMADA,OLAHG,SZESNYB,et al.AP39,A mitoehondrially targeted hydrogen sulfide donor,exerts protective effects in renal epithelial ceils subjected to oxidative stress in vitro and in acute renal injury in vivo[J].Shock,2016,45(1):88-97.
[本文引用:1]
[16]
HANCIV,EROLB,BEKTASS,et al.Effect of dexmedetomidine on testicular torsion/detorsion damage in rats[J].Urol Int,2010,84(1):105-111.
[本文引用:1]
Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in all experimental pulmonary thromboembolism model
AP39,A mitoehondrially targeted hydrogen sulfide donor,exerts protective effects in renal epithelial ceils subjected to oxidative stress in vitro and in acute renal injury
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