Ketamine reduces intestinal injury and inflammatory cell infiltration after ischemia/reperfusion in rats

Purpose  

Intestinal ischemia reperfusion (I/R) induces severe injury and significant mortality. New therapeutic interventions are needed; ketamine is an anesthetic with anti-inflammatory properties, which has shown protective effects on I/R in various organs. This study investigated effects of ketamine on intestinal I/R injury.     

Dexamethasone pretreatment alleviates intestinal ischemia–reperfusion injury

Background

Activated mast cells are involved in the pathogenesis of intestinal ischemia–reperfusion (I/R)-related injury. Dexamethasone has been widely used to protect organs from I/R injury. This study was conducted to investigate the impact of treatment with dexamethasone at different stages of the II/R process on mast cell infiltration and activity and intestinal injury.

Methods

Kunming mice were randomized and subjected to a sham surgery or the II/R induction by clamping the superior mesenteric artery for 30 min and then reperfusion. During the II/R induction, the mice were treated intravenously with dexamethasone (10 mg/kg) for 30 min before ischemia (pretreatment group), at 5 min after clamping the superior mesenteric artery (isc-treatment group), or at the beginning of perfusion (rep-treatment group), respectively. The levels of intestinal injury, mast cell infiltration and activity, tumor necrosis factor α (TNFα) and myeloperoxidase (MPO) activity in the intestines, and mouse survival rates were measured.

Results

The death rates, levels of intestinal injury, mast cell infiltration and activity, and tumor necrosis factor α and myeloperoxidase activity in the intestinal tissues from the II/R group were similar to those from the isc-treatment and rep-treatment groups of mice and were significantly higher than those from the sham group. In contrast, pretreatment with dexamethasone significantly mitigated the II/R-induced mast cell infiltration and activity, inflammation, and intestinal injury and reduced the death rates in mice.

Conclusions

Pretreatment with dexamethasone inhibits II/R injury by reducing mast cell–related inflammation in mice.     

Mast cell degranulation promotes ischemia–reperfusion injury in rat liver

Background

Mast cells (MCs) play a role in ischemia–reperfusion (I/R) injury in many organs. However, a recent study found that MCs are not involved in I/R injury in isolated rat livers that were perfused only for 1 h. The purpose of this study is to reevaluate the role of MCs in hepatic I/R injury in rat.

Materials and methods

A warm hepatic I/R injury model of 1 h ischemia followed by 24 h of reperfusion was used. MC modulation was induced via cromolyn injection or a method called MC depletion using compound 48/80. The effects of MC modulation were evaluated by toluidine blue staining and assessment of mast cell tryptase in sera. The role of MCs in I/R injury was evaluated by hematoxylin and eosin staining graded by Suzuki criteria, alanine aminotransferase and aspartate aminotransferase levels in sera, and malondialdehyde levels in liver homogenates.

Results

First, MC degranulation peaked after 2 h of reperfusion and liver damage peaked after approximately 6 h of reperfusion. Second, a method called MC depletion previously used in the skin with repeated injections of compound 48/80 worked similarly in the hepatic setting. Third, stabilization of MCs with cromolyn or depletion of MCs with compound 48/80 each decreased hepatic I/R injury. The most noticeable effects of cromolyn and compound 48/80 treatment were observed after approximately 6 h of reperfusion.

Conclusions

MC degranulation promotes hepatic I/R injury in rats.     

Fish-oil emulsion (omega-3 polyunsaturated fatty acids) attenuates acute lung injury induced by intestinal ischemia–reperfusion through Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 pathway

Background

Activated macrophage infiltration into the lungs is paramount in the pathogenesis of acute lung injury (ALI) induced by intestinal ischemia–reperfusion (I/R). Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a potent activator of the Adenosine 5′-monophosphate-activated protein kinase–sirtuin1 (AMPK/SIRT1) pathway against macrophage inflammation. We aimed to evaluate whether ω-3 PUFAs may protect against ALI induced by intestinal I/R via the AMPK/SIRT1 pathway.

Methods

Ischemia in male Wistar rats was induced by superior mesenteric artery occlusion for 60 min and reperfusion for 240 min. One milliliter per day of fish-oil emulsion (FO emulsion, containing major ingredients as ω-3 PUFAs) or normal saline (control) was administered by intraperitoneal injection for three consecutive days to each animal. All animals were sacrificed at the end of reperfusion. Blood and tissue samples were collected for analysis.

Results

Intestinal I/R caused intestinal and lung injury, evidenced by severe lung tissue edema and macrophage infiltration. Pretreatment with FO emulsion improved the integrity of microscopic structures in the intestine and lungs. Intestinal I/R induced the expression of macrophage-derived mediators (macrophage migration inhibitory factor and macrophage chemoattractant protein-1), inflammatory factors (nuclear factor κB, tumor necrosis factor α, interleukin 6, and interleukin 1β), and proapoptosis factor p66shc. There was a decrease in the expression of AMPK, SIRT1, and claudin 5. FO emulsion significantly inhibited macrophage infiltration into the lungs, inflammatory factor expression, and p66shc phosphorylation. Importantly, FO emulsion restored AMPK, SIRT1, and claudin 5 in the lungs.

Conclusions

Pretreatment with ω-3 PUFAs effectively protects intestinal and lung injury induced by intestinal I/R, reduces macrophage infiltration, suppresses inflammation, inhibits lung apoptosis, and improves the lung endothelial barrier after intestinal I/R in a manner dependent on AMPK/SIRT1. Thus, there is a potential for developing AMPK/SIRT1 as a novel target for patients with intestinal I/R–induced ALI.     

Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model

Background

Lung ischemia-reperfusion (I/R) injury plays an important role in lung transplantation. Less well known is the role of sildenafil in lung I/R injury; therefore, we attempted to determine whether sildenafil could alleviate lung apoptosis and tissue injury in a rat model.

Methods

Forty male Sprague-Dawley rats were randomized into four groups: saline + sham, saline + I/R, sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation, each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53, caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry (W/D) weight ratio.

Results

Compared with the saline + sham group, the saline + I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared with the saline + I/R group, sildenafil + I/R group had significant decreases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-α level, and W/D weight ratio but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil + sham group, there were significant increases in p53 and TNF-α expression in the sildenafil + I/R group (P < 0.05).

Conclusions

Pretreatment with sildenafil alleviates lung apoptosis and tissue injury in a rat model.     

α-Lipoic acid and ebselen prevent ischemia/reperfusion injury in the rat intestine

Purpose  Reactive oxygen species (ROS) and reactive nitrogen species (RNS), generated during tissue reperfusion, are characteristic of ischemia/reperfusion (I/R) injury. We conducted this study to evaluate the protective effect of α-lipoic acid (α-LA) and ebselen against intestinal I/R injury. Methods  Forty Sprague-Dawley rats were divided into five groups: a sham-operated group; an I/R group, subjected to intestinal ischemia for 45 min and reperfusion for 3 days; an I/R+α-LA group; an I/R+ebselen group; and an I/R+α-LA+ebselen group. We collected ileal specimens, to measure the tissue levels of malondialdehyde (MDA), protein carbonyl content (PCC), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and to evaluate the histologic changes. Results  There was a significant decrease in SOD and GPx levels, with an increase in MDA and PCC levels and intestinal mucosal injury in the intestinal I/R group (P < 0.05). Superoxide dismutase and GPx levels were significantly higher, MDA and PCC levels were significantly lower, and intestinal injury was significantly less severe in the I/R+α-LA+ebselen group than in the I/R group (P < 0.05). Although shortened villi and epithelial lifting were seen in the I/R group, only slight mucosal injury was seen in the treatment groups. Conclusion  α-Lipoic acid and ebselen played an important role in attenuating I/R injury of the intestine by scavenging ROS and RNS.     

Hydrogen-rich saline solution attenuates renal ischemia�Creperfusion injury

Purpose  

Renal ischemia–reperfusion (I/R), an important cause of acute kidney injury, is unavoidable during various types of operations, including renal transplantation, surgical revascularization of the renal artery, partial nephrectomy, and treatment of suprarenal aortic aneurysms. Exacerbation of I/R injury is mediated by reactive oxygen species (ROS). A recent study has shown that hydrogen has antioxidant properties. In this study, we tested the hypothesis that a hydrogen-rich saline solution (HRSS) attenuates renal I/R injury in a rodent model.     

Transduced PEP-1–heme oxygenase-1 fusion protein protects against intestinal ischemia/reperfusion injury

Background

Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury.

Materials and methods

PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1).

Results

Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1–treated animals.

Conclusion

Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.     

Resveratrol ameliorates subacute intestinal ischemia-reperfusion injury

Background

Resveratrol has been shown to attenuate reactive oxygen species formation and protect against ischemia-reperfusion (I/R) injury. However, the effects of resveratrol against subacute intestinal I/R injury are not clearly elucidated. Therefore, this study was designed to investigate the effects and possible protective mechanisms of resveratrol on subacute intestinal I/R injury in mice.

Methods

BALB/c mice were subjected to 1 h ischemia by occluding the superior mesenteric artery and 24 h reperfusion. Histologic injury; myeloperoxidase, superoxide dismutase, and glutathione peroxidase activity; malondialdehyde level; inducible nitric oxide synthase (iNOS), Ac-NF-κBp65, and sirtuin 1 (SIRT1) expression; NF-κB translocation; and nitric oxide (NO) production were examined in treated with or without resveratrol in the absence or presence of pharmacologic inhibitors.

Results

Resveratrol significantly ameliorated subacute intestinal I/R injury accompanied with the decrease of NO production as well as iNOS expression. In addition, resveratrol obviously upregulated the expression of SIRT1 and inhibited the activity of NF-κB. After application of iNOS inhibitor S-methylisothiourea and NF-κB inhibitor pyrrolidine dithiocarbamate, the protective effect of resveratrol was significantly augmented by attenuating iNOS and NO production, indicating that resveratrol exerted its protective effect on intestinal I/R injury via NF-κB-mediated iNOS pathway. Furthermore, the protective effect of resveratrol was correlated with SIRT1, because application of SIRT1 inhibitor nicotinamide strikingly weakened the protective effect of resveratrol.

Conclusions

Taken together, our findings showed that resveratrol protects intestinal subacute I/R injury via the SIRT1-NF-κB pathway in an iNOS-NO-dependent manner. Therefore, resveratrol has a potential clinical prospect for further development of anti-injury therapy.     

Acute Hyperglycemia Worsens Hepatic Ischemia/Reperfusion Injury in Rats

Background/Aims  

Acute hyperglycemia is known to worsen ischemia/reperfusion (I/R) injury following myocardial infarction and stroke. We investigated whether acute hyperglycemia worsens injury and amplifies the inflammatory response evoked by hepatic I/R.     

Role of glycogen synthase kinase 3β in protective effect of propofol against hepatic ischemia–reperfusion injury

Background

It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia–reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3β (GSK-3β) is known to play an important role in the oxidative stress–induced apoptosis. In this study, we investigated the role of GSK-3β and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.

Materials and methods

The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.

Results

Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells. Importantly, propofol suppressed the mitochondrial GSK-3β by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.

Conclusions

Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3β.     

Curcumin Nutrition for the Prevention of Mesenteric Ischemia-Reperfusion Injury: An Experimental Rodent Model

Background

Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-κB (NF-κB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats.

Methods

Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-α.

Results

There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-α in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05).

Conclusion

This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.     

Heparin-binding epidermal growth factor-like growth factor gene disruption is associated with delayed intestinal restitution, impaired angiogenesis, and poor survival after intestinal ischemia in mice

Purpose

We have demonstrated that administration of heparin-binding epidermal growth factor-like growth factor (HB-EGF) protects the intestines from injury. The aim of the current study was to evaluate the effect of HB-EGF gene disruption on intestinal restitution, angiogenesis, and long-term survival after intestinal ischemia/reperfusion (I/R) injury.

Methods

HB-EGF (−/−) and wild-type HB-EGF (+/+) littermate mice were subjected to 45 minutes of superior mesenteric artery occlusion followed by reperfusion. Functional recovery of the gut permeability barrier was evaluated with Ussing chamber studies, and microvessel density was evaluated immunohistochemically. Animal survival was evaluated using the Kaplan-Meier method.

Results

Histologic damage after ischemia was significantly higher in HB-EGF (−/−) mice compared with HB-EGF (+/+) mice, associated with a significantly higher number of incompetent (nonhealed, nonresurfaced) villi indicative of delayed structural healing by restitution. HB-EGF (−/−) mice had increased intestinal permeability after intestinal I/R. HB-EGF (−/−) mice had significantly lower microvessel density at 3 and 7 days after I/R, indicating that HB-EGF gene deletion resulted in delayed onset of angiogenesis. Two-week mortality rates were significantly higher in HB-EGF (−/−) mice.

Conclusions

Endogenous HB-EGF significantly enhances healing by restitution, prolongs survival, and enhances angiogenesis in mice subjected to intestinal I/R injury. These findings support our hypothesis that HB-EGF administration may improve outcome in patients with intestinal I/R injury, including necrotizing enterocolitis.     

Penehyclidine hydrochloride ameliorates renal ischemia–reperfusion injury in rats

Background

Renal ischemia–reperfusion (I/R) injury is a major cause of acute kidney failure by mechanisms that involve oxidative stress, inflammation, and apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent, possesses anti-inflammatory, antioxidative stress, and antiapoptotic effects. Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in Sprague–Dawley rats.

Materials and methods

Rats were randomly assigned to three groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated I/R. After removing the right kidney, renal I/R injury was induced by clamping the left renal artery for 45 min followed by reperfusion. The rats were administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after reperfusion. Renal function and histologic changes were assessed. Markers of oxidative stress, inflammation, and apoptosis in the kidneys were also measured.

Results

PHC treatment significantly attenuated renal dysfunction and histologic damage caused by I/R injury. The treatment also decreased malondialdehyde level and attenuated the reduction in superoxide dismutase activity in the kidney. Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear factor kappa B, and caspase 3 were lower in the PHC-treated animals.

Conclusions

PHC protected rat kidneys from I/R injury by attenuating oxidative stress, inflammatory response, and apoptosis. Thus, PHC may represent a novel practical strategy for the treatment of renal I/R injury.     

The Early Protective Effect of Glutamine Pretreatment and Ischemia Preconditioning in Renal Ischemia–Reperfusion Injury of Rat

Background

Heat shock proteins (HSP) play an important role in protecting cells against stress.

Methods

Using a rat model, we tested the hypothesis that pretreatment with glutamine (Gln) and ischemia preconditioning (IPC) increase the expression of HSP resulting in attenuation of renal ischemia/reperfusion (I/R) injury. Sprague-Dawley rats were randomized into 4 groups [group I, Gln injection (+), IPC (+); group II, Gln injection (+), IPC (−); group III, saline injection (+), IPC (+); group IV, saline injection (+), IPC (−)]. Renal HSP70 expression was determined by Western blotting and kidney function was assessed by blood urea nitrogen and serum creatinine. Renal cross-sections were microscopically examined for tubular necrosis, exfoliation of tubular epithelial cells, cast formation, and monocyte infiltration.

Results

Gln pretreatment increased intrarenal HSP expression (P = .031). In group I, tubulointerstitial abnormalities were clearly slighter compared with the other groups (P < .001).

Conclusion

Our experiments suggest that (1) a single dose of Gln could induce HSP expression and (2) IPC could relieve renal I/R injury. In addition, IPC combined with Gln pretreatment had a synergic protective effect against renal I/R injury.     

Protective effect of 2-aminoethyl diphenylborinate on acute ischemia–reperfusion injury in the rat kidney

Background

To investigate the protective effect of 2-aminoethyl diphenylborinate (2-APB) against ischemia–reperfusion (I/R) injury in the rat kidney by an experimental study.

Materials and methods

Thirty male Sprague-Dawley rats were randomly divided into the following three groups: (1) sham group, (2) I/R group, and (3) I/R + 2-APB group. Renal I/R injury was induced by clamping the left renal pedicle for 45 min after right nephrectomy, followed by 3 h of reperfusion. The therapeutic agent 2-APB was administered intravenously at a dose of 2 mg/kg 10 min before renal ischemia. Glutathione, superoxide dismutase, total antioxidant capacity, malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were measured from blood samples, and the rats were sacrificed subsequently. Tissue samples were scored histopathologically. Visualization of apoptotic cells was performed using the terminal deoxynucleotidyl transferase dUTP nick end labeling staining method.

Results

2-APB significantly reduced serum malondialdehyde, tumor necrosis factor α, interleukin 6, aspartate aminotransferase, alanine aminotransferase, and creatinine levels in the I/R injury group. However, glutathione, superoxide dismutase, and total antioxidant capacity levels increased significantly. Histopathologic scores were significantly better and the rate of apoptosis was lower in the 2-APB group.

Conclusions

2-APB reduces oxidative stress and damage caused by renal I/R injury. The results of this study demonstrate that 2-APB can be used as an effective agent against I/R injury in the kidney.     

HB-EGF augments the ability of mesenchymal stem cells to attenuate intestinal injury

Background

We have previously demonstrated that heparin-binding EGF-like growth factor (HB-EGF) and mesenchymal stem cell (MSC) administration protect the intestines from ischemia/reperfusion (I/R) injury in vivo, with amniotic fluid-derived MSC (AF-MSC) being more efficacious than bone marrow-derived MSC (BM-MSC). The goal of the current study was to determine whether the protective effects of HB-EGF were from direct effects on MSC or via alternative mechanisms.

Methods

Murine MSC were transfected with an HB-EGF plasmid or control plasmid by electroporation. Mice were subjected to segmental intestinal I/R injury and received either BM-MSC or AF-MSC either with or without exogenous HB-EGF, or BM-MSC or AF-MSC that endogenously over-expressed HB-EGF. MSC engraftment, intestinal histologic injury, and intestinal permeability were quantified.

Results

There was increased MSC engraftment into injured compared to uninjured intestine. HB-EGF increased AF-MSC engraftment into injured intestine. Administration of HB-EGF and MSC improved intestinal histology and intestinal permeability after I/R injury, with AF-MSC being most efficacious. The effect of HB-EGF on MSC was similar when the growth factor was administered exogenously, or when it was overexpressed endogenously.

Conclusions

The effect of HB-EGF on AF-MSC was similar with both exogenous administration and endogenous overexpression of the growth factor, implying that HB-EGF has a direct effect on AF-MSC. This information may assist in guiding potential future AF-MSC-based therapies for patients at risk of intestinal ischemic injuries.     

Resveratrol Alleviates Lung Ischemia and Reperfusion–Induced Pulmonary Capillary Injury Through Modulating Pulmonary Mitochondrial Metabolism

Objective

Lung ischemia and reperfusion (I/R) injury is one of the major causes of postoperative pulmonary dysfunction after cardiopulmonary surgery and thoracic organ transplantation. Recent studies suggest that lung I/R injury may be associated with defects in pulmonary mitochondrial function, in addition to damage from reactive oxygen species. In this study, we examined effects of one lung I/R injury on the other lung, and the protective efficacy of resveratrol on mitochondrial biogenesis in lungs.

Methods

Studies were performed in male Sprague-Dawley rats in 3 groups: sham-operated, lung I/R injury, and treated with resveratrol before lung I/R injury (20 mg/kg/d, orally). Lung ischemia was established by occluding the lung left hilum for 60 minutes, followed by releasing the occlusion and closing the chest. Four days after ischemia, we assessed the lung water content and protein concentration in lung lavage of the nonischemic lung; lung inflammation and pulmonary oxidative stress were assessed by leukocyte counts and tissue content of malondialdehyde (MDA), respectively. The level of mitochondrial biogenesis was determined according to PGC1-α mRNA expression.

Results

The left lung I/R injury significantly suppressed right lung PGC1-α mRNA expression, increasing pulmonary oxidative stress, lung water content, and lavage leukocyte count and protein concentration (P < .05). Resveratrol treatment attenuated lung injury as well as increasing PGC1-α mRNA expression.

Conclusions

Resveratrol treatment protects lung against I/R injury through improving mitochondrial biogenesis and reducing oxidative stress and leukocyte infiltration.     

Effect of Autologous Adipose-Derived Stem Cells in Renal Cold Ischemia and Reperfusion Injury

Objective

The aim of this study was to investigate the effect of autologous adipose-derived stem cells (ADSCs) on renal cold ischemia and reperfusion (I/R) injury via intravenous infusion on rats.

Methods

A renal cold I/R injury rat model was established. Rats were equally randomized into Sham group, Cold I/R group (cold I/R plus culture medium only), and ADSC-treated group (cold I/R plus immediate intrarenal administration of 2 × 10⁶ autologous ADSCs, followed by intravenous autologous ADSCs 6 hours after reperfusion). All rats were killed 24 hours after the I/R procedure.

Results

Serum creatinine levels were significantly reduced in the ADSC-treated group compared with the Cold I/R group (P < .01). The renal tissue in the ADSC-treated group had well conserved renal architecture compared with the Cold I/R group. The mRNA expression of tumor necrosis factor α was significantly lower and Bcl-2 was higher in the ADSC-treated group than in the Cold I/R group (P < .05).

Conclusions

Autologous ADSC infusions ameliorated renal damage undergoing cold I/R injury and improved the renal function, partly through inhibiting inflammatory reactions and reducing apoptosis.