transforming-growth-factor-alpha and Reperfusion-Injury

Hepatic ischemia/reperfusion (I/R) describes the paradox of additional tissue injury caused by reperfusion. The aim of this survey was to investigate the mRNA expression of genes exerting their inflammatory and regenerative reaction in a porcine model of I/R and extended hepatectomy.. Twelve pigs were used, weighing 30-35 kg in average, which were allocated in two groups: the I/R group with eight pigs and the sham-operated (control) one with four pigs. The I/R group underwent portacaval anastomosis and Pringle maneuver followed by extended hepatectomy. The hepatoduodenal ligament was occluded for 150 min and the liver remnant was reperfused for 24 hours. Blood samples were steadily received throughout the surgical procedure, where hepatic biopsies were taken for pathological evaluation. Animals were sacrificed in 24 hours after the onset of reperfusion.. Between the two groups, statistically significant differences were noticed in serum values of AST, ALT, ALP, and total bilirubin in the early and late phase of reperfusion. The mRNA expression of iNOS, IL-1b, and TGF-a did not increase significantly in the I/R group. Conversely, the mRNA modification of IL-6, STAT-3, and E-selectin demonstrated significantly increased expression in I/R animals.. In the present survey, a new I/R swine model was proposed and specific parameters were analyzed, revealing differences between the study groups.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Bilirubin; Biopsy; Disease Models, Animal; E-Selectin; Female; Hepatectomy; Inflammation; Interleukin-1beta; Interleukin-6; Ischemia; Liver; Liver Diseases; Liver Regeneration; Nitric Oxide Synthase Type II; Reperfusion Injury; RNA, Messenger; STAT3 Transcription Factor; Swine; Transforming Growth Factor alpha

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a hypoxia-inducible neuroprotective protein that also stimulates proliferation of neuronal precursor cells. In this study, we investigated the possible role of HB-EGF in ischemia and reperfusion injury by measuring the changes in its mRNA expression following focal cerebral ischemia. We also examined neural damage after a middle cerebral artery occlusion (MCAO) and reperfusion in ventral forebrain specific HB-EGF knockout (KO) mice. The levels of HB-EGF mRNA in the cerebral cortex of wild-type (WT) mice were significantly increased 3-24 h after MCAO and reperfusion. Cerebral infraction in HB-EGF KO mice was aggravated at 1 day and 6 days after MCAO and reperfusion compared with WT mice. The number of terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL) and an oxidative stress marker, 8-hydroxy-2'-deoxyguanosine (8-OHdG) positive cells, were higher in HB-EGF KO mice than in WT mice. On the other hand, fewer bromodeoxyuridine (BrdU) positive cells were found in the subventricular zone in HB-EGF KO mice compared with WT mice. These results indicate that HB-EGF may play a pivotal role in ischemia and reperfusion injury and that endogenously synthesized HB-EGF is necessary for both the neuroprotective effect and for regulation of cell proliferation in the subventricular zone.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult Stem Cells; Analysis of Variance; Animals; Brain Infarction; Bromodeoxyuridine; Cerebral Ventricles; Deoxyguanosine; Disease Models, Animal; Epidermal Growth Factor; Gene Expression Regulation; Heparin-binding EGF-like Growth Factor; In Situ Nick-End Labeling; Infarction, Middle Cerebral Artery; Intercellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Prosencephalon; Reperfusion Injury; RNA, Messenger; Transforming Growth Factor alpha

Hepatic ischemia/reperfusion injury can lead to remote lung injury by inducing oxidative stress and inflammation. this study aims to investigate whether support of liver function with a bioartificial liver can attenuate remote lung injury after extended hepatectomy.. Fourteen domestic pigs were subjected to liver ischemia for 150 minutes and 70-75% hepatectomy. Six hours after initiation of hepatic reperfusion the animals were randomly allocated to a 6-hour treatment with a bioartificial liver (group b, n=7) or observation (group C, n=7). Hemodynamic and metabolic parameters were monitored for 24 hours following reperfusion. Lung biopsies were used for histological, nitrotyrosine and mrNA analysis.. Oxygenation gradually deteriorated in group C, but was not significantly impaired in group b. Histological evaluation revealed improvements in alveolar collapse, necrotized pneumonocytes and lymphocyte infiltration in group b. Nitrotyrosine content of the lung was lower in group b compared to group C (55+/-12 vs. 132+/-22 nM/mg protein, p<0.01). Lung mrNA expression of interleukin-6, Stat-3 and E-selectin also decreased in group b. Expression of transforming growth factor-alpha mrNA did not differ between groups.. Application of a bioartificial liver was associated with improvement in several parameters of post-hepatectomy lung injury. the mechanisms appear to involve reduced nitrosative stress and attenuation of the native inflammatory process in the lung.

Topics: Animals; Blood Pressure; Cytokines; Disease Models, Animal; E-Selectin; Heart Rate; Hepatectomy; Hepatocytes; Liver, Artificial; Lung; Necrosis; Nitric Oxide Synthase Type II; Reperfusion; Reperfusion Injury; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; STAT3 Transcription Factor; Swine; Tidal Volume; Transforming Growth Factor alpha

Epidermal growth factor (EGF) signals enterocyte proliferation via extracellular regulated kinases (ERKs). Because glutamine is required for EGF-stimulated proliferation and stimulates ERKs in intestinal cell culture, we hypothesized that glutamine and the EGF-related peptide transforming growth factor-alpha (TGF-alpha) would synergistically enhance repair associated with stimulation of ERKs.. Thiry-Vella loops were created in juvenile pigs. One half of the loop was subjected to 2 hours of ischemia, and the other half served as control. Loops were infused daily with Ringer's solution containing 140 mmol/L glucose, 140 mmol/L glutamine, 140 mmol/L glucose plus 60 micrograms/L TGF-alpha, or 140 mmol/L glutamine plus 60 micrograms/L TGF-alpha.. After 2 hours of ischemia, complete villous epithelial sloughing was present. By 18 hours, villous epithelium had fully restituted, but villi remained stunted until 144 hours after injury. Glutamine + TGF-alpha triggered sustained increases in ERK activity compared with glucose-treated tissues (maximal at 18 hours), whereas glutamine alone or glucose + TGF-alpha caused only transient elevations in ERK activity. By 72 hours, villous surface area had increased to normal values with glutamine plus TGF-alpha treatment, whereas villi remained stunted with glucose alone, glutamine alone, or glucose plus TGF-alpha.. Glutamine plus TGF-alpha treatment restored mucosal architecture within 72 hours of severe ischemic injury associated with sustained elevations in ERK activity.

Topics: Animals; Enzyme Activation; Extracellular Space; Female; Glucose; Glutamine; Ileum; Intestinal Mucosa; Male; Microvilli; Phosphotransferases; Reperfusion Injury; Swine; Time Factors; Transforming Growth Factor alpha