Expression of aquaporin 3 and aquaporin 9 is regulated by oleic acid through the PI3K/Akt and p38 MAPK signaling pathways / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the effect of oleic acid (OA) on expression of aquaglyceroporin genes, AQP3 and AQP9, in hepatocyte steatosis and to investigate the underlying molecular mechanisms using an in vitro system.</p><p><b>METHODS</b>HepG2 cells were treated with OA at different concentration to establish in vitro models of nonalcoholic hepatocyte steatosis. The corresponding extents of hepatic steatosis modeling were assessed by oil red O staining and optical density (OD) measurements of the intracellular fat content. The model lines were then treated with inhibitors of the PI3K/Akt and p38 MAPK signaling pathway factors and effects on AQP3/9 expression was measured by real time RT-PCR and western blotting.</p><p><b>RESULTS</b>The fat concentration, indicative of hepatic steatosis, increased in conjunction with increased concentrations of OA (0 less than 250 less than 500 mumol/L). OA exposure also down-regulated AQP3 mRNA and up-regulated AQP9 mRNA levels in a concentration-dependent manner. The most robust changes in expression occurred in response to the 500 mumol/L concentration of OA for both AQP3 (0.47+/-0.18; t = 4.5450, P less than 0.05) and AQP9 (1.57+/-0.21; t = 3.0306, P less than 0.05). Treatment with OA + PI3K pathway inhibitor (LY294004) significantly decreased AQP9 mRNA expression (4.55+/-0.62) as compared to the control group (1.00+/-0.10; t = 9.7909, P less than 0.01), that 500 mumol/L OA group (2.43+/-0.53; t = 4.5018, P less than 0.05), and the LY294002 group (1.90+/-0.16; t = 7.1683, P less than 0.01). Treatment with p38 MAPK pathway inhibitor (SB230580) significantly increased the OA-suppressed level of AQP3 mRNA to the level detected in the control group (1.27+/-0.11; t = 5.7455, P less than 0.01) and decreased the OA-stimulated AQP9 mRNA (0.38+/-0.09; t = 6.5727, P less than 0.01). No significant changes in mRNA expression of AQP3/9 were observed with inhibition of the ERK1/2 and JNK signal transduction pathways. The OA-induced changes in protein expression levels of AQR3 and AQP9 followed a similar trend of the genes. Finally, OA suppressed the level of phosphorylated Akt (from 0.21+/-0.02 to 0.13+/-0.03; t = 3.8431, P less than 0.05) but elevated the level of phosphorylated p38 (from 0.58+/-0.06 to 1.02+/-0.10; t = 12.5289, P less than 0.01). Again, OA treatment produced no significant affect on ERK1/2 and JNK phosphorylation.</p><p><b>CONCLUSION</b>OA down-regulates AQP3 expression by stimulating the p38 MAPK signaling pathway, and up-regulates the AQP9 by blocking the PI3K/Akt pathway and activating the p38 MAPK signaling pathway.</p>

Effects of insulin and LY294002 inhibitors of PI3K on the regulations and expression of aquaporin 9 in normal liver cells / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To explore the effects of insulin on the expression and the regulatory pathway of AQP9 in normal human liver cells.</p><p><b>METHODS</b>Normal human liver cells L02 were cultured and treated with PI3K inhibitor LY294002, AKT inhibitor A-443654, MAPK inhibitors SB2030580 and insulin at different concentrations respectively. The AQP9 mRNA and protein expressions were detected with semi-quantitative RT-PCR and Western blot respectively.</p><p><b>RESULTS</b>The insulin (100 nmol/L approximately 500 nmol/L) treatment decreased the expression of AQP9 in normal human liver cells (P less than 0.05) concentration dependently, and the expression of AQP9 began to reduce from 3 hours of insulin stimulation (P less than 0.05), especially at insulin treatment for 12 hours (P less than 0.05); Incubated with the selective inhibitor of PI3K (LY294002) and AKT (A-443654), the inhibitory effects of insulin on AQP9 expression decreased (P less than 0.05); but it did not change significantly by blocking the MAPK signaling pathway.</p><p><b>CONCLUSION</b>The insulin treatment inhibited the expression of AQP9 and the PI3K/akt signal transduction pathway was involved in the mechanism.</p>

Efficacy of endoscopic variceal ligation and its correlation with liver function / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the efficacy of endoscopic variceal ligation and its correlation with liver function.</p><p><b>METHODS</b>322 patients received EVL (endoscopic variceal ligation) and 34 patients with PDP (pericardial devascularization procedure) were retrospectively analyzed and divided into groups A, B and C. These patients were then subdivided into bleeding and non-bleeding subgroups according to Child-Pugh scores of liver function and history of upper gastrointestinal bleeding. The bleeding rate and mortality were contrasted between EVL and PDP. Liver function, Platelet count, leucocyte count and spleen thickness of before and after ligation were contrasted in EVL.</p><p><b>RESULTS</b>The bleeding rate and mortality were 1.7%, 3.4%, 7.0%; 0%, 5.1%, 8.1% in EVL group and 9.1%, 14.3%, 100.0%; 0%, 9.5%, 50.0% in PDP group, respectively. Variceal obliteration needed means of 2.1+/-0.7, 3.1+/-0.8 and 4.2+/-1.2 sessions in A, B and C ligation groups, respectively (F = 41.2, P is less than 0.01). On subgroup analysis, the numbers of ligation session were 2.6+/-0.7, 3.2+/-0.9 and 4.3+/-1.1 in A, B and C bleeding subgroup (F = 39.3, P value is less than 0.01) and 2.0+/-0.6, 2.7+/-0.6, and 2.9+/-0.4 in A, B and C non-bleeding subgroup, respectively (F = 17.0, P value is less than 0.01). ALT, AST, Platelet count and leucocyte count reduced significantly, spleen thickness increased remarkably in bleeding subgroup after ligation.</p><p><b>CONCLUSION</b>The efficacy of EVL was significantly negatively correlated with liver function and prior to pericardial devascularization procedure. EVL had no effect on liver function but might increase spleen thickness and aggravate hypersplenism. EVL was recommended especially for the bleeding liver cirrhosis patients with Child B and C scores.</p>

The effectiveness of endoscopic variceal ligation in patients with different grades of liver function / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the effectiveness of endoscopic variceal ligation (EVL) in patients with different grades of liver function.</p><p><b>METHODS</b>MELD scores were determined for 156 patients before their EVL operations. After the EVL these patients were followed-up and their survival rates were analyzed.</p><p><b>RESULTS</b>Fifty percent of the patients whose MELDs were less than or equal to 7 survived longer than 45 months after the EVL; in those with MELDs between 7 and 9, 50% of the patients survived 47.34 months; however, the figure for those whose MELD were more than 9 survived only 24.89 months. In the first two groups, 50% of the patient' survival duration was significantly longer than that of the third group. The difference was statistically significant.</p><p><b>CONCLUSION</b>EVL becomes an effective clinical way to treat hemorrhage of esophagus varicose veins. The survival rate for this procedure is directly correlated with the liver function of the patient before the EVL.</p>

Evaluation of the effects of dense endoscopic ligation for bleeding esophageal varices / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the short-term and long-term effects of dense endoscopic variceal ligation (DEVL) for bleeding esophageal varices.</p><p><b>METHODS</b>Patients with acute or with a history of esophageal variceal bleeding underwent regular DEVLs with a 2-3 week interval between 2 sessions until their varices disappeared at the lower 5-6 cm part of the esophagus. Follow-up study and gastroscopy were performed at 3, 6 and 12 months after the final DEVL in all patients. The results at 3 months were classified as short-term effects and those after 6 months as long-term ones.</p><p><b>RESULTS</b>126 patients underwent DEVLs with 403 sessions and 3641 ligations; each patient was ligated with a mean of 3.2 sessions and at 28.9 points. The cure rate of acute variceal bleeding was 100.0%; short-term rate of variceal eradication was 94.4% and variceal rebleeding occurred in 3.9% patients. After a mean of 22.3 months follow-up period, the recurrence of esophageal varices was observed in 11.9% patients, but the variceal rebleeding rate was only 3.2% and no patients died from it.</p><p><b>CONCLUSION</b>DEVL was very useful and effective in both short-term and long-term variceal eradication and prevention of variceal rebleeding.</p>