Propofol alleviates intestinal ischemia/reperfusion injury in rats through p38 MAPK/NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the influences of propofol on intestinal ischemia/reperfusion (I/R) injury in rats through the p38 mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. MATERIALS AND METHODS: The models of intestinal I/R injury were first successfully established. All rats were randomly divided into 4 groups, namely, S group, I/R group, P group and P + S group. Pathological-morphological changes, injury score and wet-to-dry weight ratio of intestinal tissues as well as oxidative stress indexes in each group of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the levels of inflammatory factors such as creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group of rats. Furthermore, Western blotting (WB) assay was applied to determine the protein expression levels of p38 MAPK and NF-κB in different groups. RESULTS: Intestinal tissue injury was the severest in I/R group, with the infiltration of massive inflammatory cells and oozing of blood (Figure 1A, I/R). Compared with those in I/R group, the infiltration of inflammatory cells and damage to intestinal villi were notably relieved in P group and P + S group, revealing that the intestinal mucosal injury was remarkably repaired in P group and P + S group (Figure 1A, P). Moreover, the intestinal tissue injury score was evidently higher in I/R group, P group and P + S group than that in S group (p<0.05). However, it was markedly lower in P group and P + S group than that in I/R group (p<0.05). I/R group, P group and P + S group exhibited significantly increased wet-to-dry weight ratio of intestinal tissues in comparison with S group (p<0.05). However, P group and P + S group exhibited distinctly lower wet-to-dry weight ratio of intestinal tissues than I/R group (p<0.05). The content of malondialdehyde (MDA) was reduced prominently, while that of superoxide dismutase (SOD) was elevated significantly in P group and P + S group in contrast with those in I/R group (p<0.05). On the contrary, P + S group displayed remarkably lower MDA content and higher SOD content than P group (p<0.05). The levels of CK-MB, TNF-α and IL-6 in the blood rose markedly in I/R group compared with those in S group (p<0.05). However, they declined evidently in P group and P + S group in contrast with those in I/R group (p<0.05). Besides, the protein expression level of phosphorylated p38 MAPK was significantly higher in I/R group, P group and P + S group than that in S group (p<0.05). However, no significant difference was observed in the protein expression of total p38 MAPK among the four groups (p>0.05). However, the protein expression level of phosphorylated p38 MAPK was distinctly down-regulated in P group and P + S group in comparison with that in I/R group (p<0.05). Finally, I/R group, P group and P + S group had a prominently higher protein expression level of NF-κB than S group (p<0.05). However, P group and P + S group exerted a significantly lower protein expression level of NF-κB than I/R group (p<0.05). CONCLUSIONS: Propofol decreases the release of inflammatory factors and alleviates intestinal edema by inhibiting the p38 MAPK/NF-κB signaling pathway, thereby mitigating and treating the intestinal I/R injury in rats.

Sevoflurane ameliorates adriamycin-induced myocardial injury in rats through the PI3K/Akt/GSK-3ß pathway.

OBJECTIVE: The aim of this study was to explore the effects of sevoflurane (SEV) pretreatment on Adriamycin (ADR)-induced myocardial injury through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway. MATERIALS AND METHODS: A total of 24 rats weighing 200-250 g were divided into four groups, including: control group (C group), ADR injection group (ADR group), SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group). H9c2 cells were cultured in vitro and were divided into control group (C group), ADR treatment group (ADR group), and SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group) as well. Next, the content of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum was detected via Enzyme-Linked Immunosorbent Assay (ELISA). Hematoxylin-eosin (HE) staining assay was performed to determine the severity of myocardial injury. Meanwhile, the apoptosis rate of cells was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Additionally, Western blotting (WB) was employed to measure the protein expression levels of phosphorylated (p)-GSK-3ß, p-PI3K, Akt and p-Akt. RESULTS: Compared with C group, ADR significantly increased the content of AST, LDH and CK in the serum (p<0.01), reduced protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), increased apoptosis rate (p<0.01), and induced myocardial injury. SEV pretreatment significantly alleviated the effect of ADR, manifested as significantly lowered content of AST, LDH and CK in the serum (p<0.01), distinctly elevated protein expression levels of p-GSK-3ß, p-PI3K and p-Akt (p<0.01), notably reduced apoptosis rate (p<0.01), and relieved myocardial injury. LY294002 remarkably inhibited the protective effect of SEV against myocardial injury (p<0.01) CONCLUSIONS: SEV is able to prominently ameliorate ADR-induced myocardial injury by regulating the phosphorylation level of the PI3K/Akt/GSK-3ß signaling pathway.

Polyglycolic Acid-islet grafts improve blood glucose and insulin concentrations in rats with induced diabetes.

Pancreatic islet transplantation is a promising therapeutic treatment for type 1 diabetes mellitus. In the present study, we cocultured islets with or without a polyglycolic acid (PGA) fibrous scaffold for 5 days and transplanted the PGA-islet grafts into the leg muscles of Wistar rats with streptozotocin-induced diabetes; controls were injected with saline. The results showed that the blood glucose concentrations of the group given islets embedded with the PGA scaffold were lower than those without the scaffold or controls. On the other hand, the insulin content of the PGA-islet group was higher at all 5 time points compared with the insulin contents of the other 2 groups. After transplantation, many islets in the PGA-islet grafts showed normal morphology (as seen under the scanning electron microscope) and were surrounded by red blood cells. A fibrous extracellular matrix was visible around the PGA-islet grafts. These results demonstrated that PGA-islet grafts improved blood glucose and insulin concentrations in rats with induced diabetes.