title: [Effect of calcium-independent phospholipase A(2) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance].
abstract: Objective:To investigate the effect of calcium-independent phospholipase A(2) (iPLA(2)) inhibitor in reducing hepatocyte lipoapoptosis and improving insulin resistance.Methods:A total of 28 male Sprague-Dawley rats were randomly divided into the following three groups: 12 rats in group I (normal control group) were given normal diet for 18 weeks; 8 rats in group II (non-alcoholic fatty liver disease model group) were given high-fat diet for 18 weeks; 8 rats in group III (iPLA(2) inhibitor group) were given high-fat diet for 18 weeks and intraperitoneal injection of the iPLA(2) inhibitor bromoenol lactone 150 μg/kg once every other day since week 15 (14 times of injection in total). All the rats were sacrificed at the same time, and body weight and liver weight were measured. Blood lipids, serum enzymes, fasting blood glucose, fasting insulin, free fatty acid, and serum iPLA(2) concentration were measured in each group, and liver pathological changes were evaluated. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to measure the level of hepatocyte apoptosis and the apoptotic index was calculated. Quantitative PCR was used to measure the mRNA expression of iPLA(2). The Student-Newman-Keuls test and the chi-square test were used for comparison of parameters between groups I, II, and III.P< 0.05 was considered statistically significant.Results:Compared with group I, group II had significant increases in triglyceride (0.75±0.05 mmol/L vs 1.20±0.13 mmol/L,P< 0.05), cholesterol (1.50±0.12 mmol/L vs 2.94±0.34 mmol/L,P< 0.05), low-density lipoprotein (0.65±0.06 mmol/L vs 1.30±0.16 mmol/L,P< 0.05), free fatty acid (0.58±0.09 mEq/L vs 0.80±0.20 mEq/L,P< 0.05), fasting blood glucose (4.85±0.22 mmol/L vs 6.94±0.65 mmol/L,P< 0.05), and fasting insulin (0.89±0.52 mmol/L vs 1.29±0.52 mmol/L,P< 0.05), and a significant reduction in the insulin sensitivity index (0.52±0.21 vs 0.27±0.11,P< 0.05); group II also had significant inflammation and fatty degeneration shown by liver pathology, and compared with group I, group II had significant increases in apoptotic cells and apoptotic index (0.58%±0.17% vs 39.69%±4.96%,P< 0.05). Compared with group I, group II had significant increases in serum iPLA(2) concentration (2.92±0.08 ng/ml vs 3.28±0.14 ng/ml,P< 0.05) and the mRNA expression of iPLA(2) in the liver (1.07±0.18 vs 7.68±0.49,P< 0.05). Compared with group II, group III had a lower level of hepatocyte apoptosis, a significant reduction in apoptotic index (39.69%±4.96% vs 24.80%±2.53%,P< 0.05), significant reductions in serum iPLA(2) concentration (3.28±0.14 ng/ml vs 2.64±0.24 ng/ml,P< 0.05) and the mRNA expression of iPLA(2) in the liver (7.68±0.49 vs 2.60±0.36,P< 0.05), significant reductions in fasting insulin (1.29±0.52 mmol/L vs 0.80±0.09 mmol/L,P< 0.05) and fasting blood glucose (6.94±0.65 mmol/L vs 5.18±0.35 mmol/L,P< 0.05), and a significant increase in insulin sensitivity index (0.27±0.11 vs 0.45±0.09,P< 0.05).Conclusion:There is a significant increase in the expression of iPLA(2) in rats with non-alcoholic fatty liver disease, and iPLA2 inhibitor can reduce hepatocyte lipoapoptosis and improve insulin resistance.
authors.affiliation: Department of Pediatrics, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo 315040 China.
authors.forename: H B
authors.initials: HB
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, The Affiliated Children's Hospital, College of Medicine, Zhejiang University, Hangzhou 310051, China.
authors.forename: J F
authors.initials: JF
authors.lastname: Fu
authors.affiliation: Department of Endocrinology, The Affiliated Children's Hospital, College of Medicine, Zhejiang University, Hangzhou 310051, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The Affiliated Children's Hospital, College of Medicine, Zhejiang University, Hangzhou 310051, China.
authors.forename: L R
authors.initials: LR
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D022781:Hepatocytes / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D007328:Insulin; D008055:Lipids; D064801:Phospholipase A2 Inhibitors; D014280:Triglycerides; D002784:Cholesterol; D054467:Phospholipases A2; D002118:Calcium
keywords: Fatty liver, non-alcoholic; Insulin; Rats