D4F alleviates macrophage-derived foam cell apoptosis by inhibiting the NF-κB-dependent Fas/FasL pathway.

This study was designed to explore the protective effect of D4F, an apolipoprotein A-I mimetic peptide, on nuclear factor-κB (NF-κB)-dependent Fas/Fas ligand (FasL) pathway-mediated apoptosis in macrophages induced by oxidized low-density lipoprotein (ox-LDL). Our results showed that ox-LDL induced apoptosis, NF-κB P65 nuclear translocation and the upregulation of Fas/FasL pathway-related proteins, including Fas, FasL, Fas-associated death domain proteins (FADD), caspase-8 and caspase-3 in RAW264.7 macrophages, whereas silencing of Fas blocked ox-LDL-induced macrophage apoptosis. Furthermore, silencing of P65 attenuated macrophage apoptosis and the upregulation of Fas caused by ox-LDL, whereas P65 expression was not significantly affected by treatment with Fas siRNA. D4F attenuated the reduction of cell viability and the increase in lactate dehydrogenase leakage and apoptosis. Additionally, D4F inhibited ox-LDL-induced P65 nuclear translocation and upregulation of Fas/FasL pathway-related proteins in RAW264.7 cells and in atherosclerotic lesions of apoE-/- mice. However, Jo2, a Fas-activating monoclonal antibody, reversed the inhibitory effect of D4F on ox-LDL-induced cell apoptosis and upregulation of Fas, FasL and FADD. These data indicate that NF-κB mediates Fas/FasL pathway activation and apoptosis in macrophages induced by ox-LDL and that D4F protects macrophages from ox-LDL-induced apoptosis by suppressing the activation of NF-κB and the Fas/FasL pathway.

Effects of neurolytic celiac plexus block on liver regeneration in rats with partial hepatectomy.

Liver regeneration is the basic physiological process after partial hepatectomy (PH), and is important for the functional rehabilitation of the liver after acute hepatic injury. This study was designed to explore the effects of neurolytic celiac plexus block (NCPB) on liver regeneration after PH. We established a model of PH in rats, assessing hepatic blood flow, liver function, and serum CRP, TNF-α, IL-1ß and IL-6 concentrations of the residuary liver after PH. Additionally, histopathological studies, immunohistochemistry, and western blotting were also performed. Our results indicated that NCPB treatment after PH improved liver regeneration and survival rates, increased hepatic blood flow, reduced hepatocyte damage, decreased the secretion and release of inflammatory cytokines, increased the expression of B cell lymphoma/leukemia-2 (Bcl-2), and decreased the expression of Bcl-2 associated X protein (Bax). Additionally, Western blotting revealed that the expression of NF-κB p65 and c-Jun were decreased in liver after NCPB. In conclusion, the results of our present study indicate that NCPB treatment has a favorable effect on liver regeneration after PH. We suggest that NCPB can be utilized as an effective therapeutic method to help the functional rehabilitation of the liver after acute hepatic injury or liver cancer surgery.

[Influence of gastric bypass surgery on hepatic gluconeogenesis in type 2 diabetic Goto Kakizaki rats].

OBJECTIVE: To investigate the influence and significance of gastric bypass surgery on hepatic gluconeogenesis in type 2 diabetic Goto Kakizaki(GK) rats. METHODS: Forty GK rats were randomly divided into Roux-en-Y gastric bypass group(group A) and sham operation group(group B). Differences in glucose tolerance experiment(OGTT) at preoperative and postoperative 1, 2 and 4 weeks were compared and weight was recorded. Glycated hemoglobin levels were measured preoperatively and 4 weeks postoperatively. The animals were sacrificed 4 weeks after surgery and liver tissues were harvested to detect the relative expression of mRNA and protein of glucose 6 phosphatase(G-6-P) and phosphoenol pyruvate kinase(PEPCK) with RT-PCR and Western blot. RESULTS: Fasting blood glucose levels were 6.5, 4.9, and 4.7 mmol/L in group A, and were 10.3, 10.4, and 12.5 mmol/L in group B, and the differences between two groups were statistically significant(P<0.05). The blood glucose level at 2 h after stomach lavage were 8.3, 6.4 and 5.5 mmol/L in group A, and were 21.4, 23.8 and 24.7 mmol/L in group B at postoperative 1, 2, 4 weeks, and the differences between two groups were statistically significant(P<0.05). The glycosylated hemoglobin at postoperative 4 weeks was(6.8±1.0)%, significantly lower than that in group B[(7.9±0.8)%, P<0.05]. Hepatic G-6-P and PEPCK mRNA relative expression at postoperative 4 weeks was reduced by 21.0% and 25.9% respectively as compared to group B, and the protein expression reduced as well. Immunohistochemistry showed that hepatic glycogen sedimentary in group A increased significantly. CONCLUSION: The relative mRNA and protein level of key enzymes of hepatic gluconeogenesis are significantly decreased after Roux-en-Y gastric bypass surgery and hepatic gluconeogenesis is reduced, which may be a potential mechanism of the decrease of blood glucose.

Percutaneous catheter drainage in combination with choledochoscope-guided debridement in treatment of peripancreatic infection.

AIM: To introduce and evaluate the new method used in treatment of pancreatic and peripancreatic infections secondary to severe acute pancreatitis (SAP). METHODS: A total of 42 SAP patients initially underwent ultrasound-guided percutaneous puncture and catheterization. An 8-Fr drainage catheter was used to drain the infected peripancreatic necrotic foci for 3-5 d. The sinus tract of the drainage catheter was expanded gradually with a skin expander, and the 8-Fr drainage catheter was replaced with a 22-Fr drainage tube after 7-10 d. Choledochoscope-guided debridement was performed repeatedly until the infected peripancreatic tissue was effectively removed through the drainage sinus tract. RESULTS: Among the 42 patients, the infected peripancreatic tissue or abscess was completely removed from 38 patients and elective cyst-jejunum anastomosis was performed in 4 patients due to formation of pancreatic pseudocysts. No death and complication occurred during the procedure. CONCLUSION: Percutaneous catheter drainage in combination with choledochoscope-guided debridement is a simple, safe and reliable treatment procedure for peripancreatic infections secondary to SAP.

[Hepatocellular glycogen alleviates hepatic ischemia reperfusion injury and its relationship to ICAM-1 gene expression].

OBJECTIVE: To investigate if higher hepatocellular glycogen contents can alleviate hepatic ischemia reperfusion injury and its relationship to ICAM-1 gene expression in hepatic sinusoidal cells (HSCs). METHODS: Twenty-one rabbits fed with a standard diet were randomly divided into three groups (n=7 in each). All the animals were subjected to hepatic ischemia reperfusion injury then sacrificed. Before the injury, group A rabbits fasted for 24 hours; group C rabbits had 6 intravenous glucose solution (25%, 20 ml) injections, 4 hours between two injections. Hepatic enzymological changes, hepatic ICAM-1 mRNA expressions and leukocytic counts in the sinusoids were observed. RESULTS: The liver glycogen contents of the three groups were significantly different. Livers of group A had higher contents of glycogen (9.85+/-0.91 mg/g. wet tissue); in group B they were 38.93+/-5.72; and in group C they were 48.31+/-6.58. Group C animals had the slightest liver function damage. There were no differences in the pre- and post-ischemic ICAM-1 mRNA contents in the three groups. However, livers with a higher content of glycogen showed less expression of ICAM-1 mRNA (group A: 1.398+/-0.365 ng/mg wet tissue; group B: 0.852+/-0.297; group C: 0.366+/-0.183) and lower leukocytic counts. The relationship analysis showed a negative relationship between hepatocellular glycogen and hepatic ICAM-1 mRNA contents (r= -0.965, P less than 0.01). CONCLUSIONS: Hepatocellular glycogen is important in protecting liver ischemic reperfusion injury. Also hepatocellular glycogen decreases the expression of ICAM-1 mRNA of HSCs.

[Perspective of pre-operational jaundice-reducing indication in carcinoma of head of pancreas].

OBJECTIVE: To explore the necessity, advantages and disadvantages of reducing the Icterus Index before operation in carcinoma of the head of pancreas. METHODS: A total of 183 patients with serum total bilirubin (TB) level higher than 220 micromol/L were randomized into 2 groups: jaundice-reducing group (92 patients) and non-reducing group (91 patients). In jaundice-reducing group, all the patients were performed ultrasound-guided percutaneous transhepatic bile duct drainage (UPTBD) and endoscopic nasobiliary drainage (ENBD). The jaundice-reducing group was operated on 3 weeks after tube placement. In non-reducing group, all the patients underwent operations only after general pre-operation routine preparation within 5 days after admission. The operation and post-operation recovery in the two groups was investigated and compared. RESULTS: In jaundice-reducing group, the level of TB decreased to 120 micromol/L from 279 micromol/L in 89 patients after biliary drainage. Of the 89 patients, pancreatoduodenectomy was successfully performed in 39 (43.8%), 47 (52.8%) underwent simple internal drainage and the other 3 were just explored. The average blood loss was 250 ml (110 - 980 ml), complications were found in 8 patients (9.0%) and one died. In non-reducing group, pancreatoduodenectomy was successfully performed in 24 (26.4%), simple internal drainage in 58 patients (63.7%) and exploration in 9 (9.9%). The average blood loss was 480 ml (320 - 1750 ml), complications were found in 19 patients (20.9%) and 4 died. In the non-reducing group, the patients with complications were older than those without complications, and the TB level was higher. The excision rate of carcinoma, incidence rate of complications and hospital time in patients whose TB decreased over 30% weekly after reducing the Icterus Index were all better than those of the rest. CONCLUSIONS: It is necessary to reduce the Icterus Index before operation in the patients with carcinoma of head of pancreas complicated with serious jaundice, especially for the elder, which can not only reduce the blood loss but also make operations safer and increase cure rate, in addition. And whether the Icterus Index decreases smoothly with biliary drainage can be used to predict the operational risk, effect and prognosis.