Research on the protection effect of pioglitazone for non-alcoholic fatty liver disease (NAFLD) in rats / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>The prevalence of non-alcoholic fatty liver disease (NAFLD) has markedly increased. Insulin resistance has been implicated in the pathogenesis of NAFLD. This study was aimed at observing the relationship between insulin resistance and NAFLD, and evaluating the role of pioglitazone (PGZ) acting as insulin-sensitizing agents in the prevention and treatment of rat fatty liver induced by high fat feeding.</p><p><b>METHODS</b>The rats were separated randomly into 6 groups: model group I were fed high fat diet for 8 weeks, PGZ prevention group were given PGZ 4 mg/(kg.d) simultaneously, while control group I were fed normal food for 8 weeks; model group II were fed high fat diet for 16 weeks, PGZ treatment group were given PGZ 4 mg/(kg.d) orally simultaneous with high fat diet for 8 weeks after high fat feeding for 8 weeks, control group II were fed normal food for 16 weeks. The rats were sacrificed after 8 weeks and 16 weeks respectively. Liver weight, body weight, serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), tumor necrosis factor alpha (TNF-alpha), fasting blood glucose (FBG), fasting plasma insulin (FINS), HOMA (homeostasis model assessment) insulin resistance index (HOMA-IR), and the liver histology of rats of all groups were assayed.</p><p><b>RESULTS</b>After 8 weeks, the liver in model group I showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration, liver indexes and serum levels of ALT, AST, ALP, TNF-alpha were significantly increased (P<0.05) compared with control group I. Whereas, the degree of hepatic injury was attenuated in PGZ prevention group, liver indexes and serum levels of ALT, ALP were significantly decreased (P<0.05) compared with model group I. After 16 weeks, notable steatosis, and lobular inflammation were observed in model group II rat liver, while the degree of hepatic injury was attenuated in the PGZ treatment group. Liver index, serum levels of ALT, AST, ALP, FINS and HOMA-IR were significantly increased (P<0.05) in model group II compared with control group II. Whereas, in PGZ treatment group, serum levels of AST and FINS showed decreasing tendency, liver indexes, serum levels of ALT, ALP, TNF-alpha and HOMA-IR were significantly decreased compared with model group II.</p><p><b>CONCLUSION</b>Insulin resistance plays a role in the pathogenesis of NAFLD in rats. Pioglitazone can attenuate insulin resistance and biochemical and histological injury in high fat-induced fatty liver in rats.</p>

Evaluation of leptin receptor Lys109Arg polymorphism in patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate whether leptin receptor Lys109Arg polymorphism influences non-alcoholic fatty liver disease.</p><p><b>METHODS</b>Genomic DNA samples were extracted from blood of subjects who had received a physical examination. Genotyping was performed using oligonucleotide microarray and these fluorescence labeled PCR-amplified fragments were hybridized to allele-specific oligonucleotide probes. The relevant mutation was confirmed by sequencing analysis.</p><p><b>RESULTS</b>A total of 180 subjects (109 males and 71 females) were included in the study, 117 of them had fatty liver disease and the other 63 had no liver problems and served as healthy controls. There were 144 (80%) subjects with GG genotype (Arg109Arg), 33 (18.3%) with GA genotype (Lys109Arg) and 3 (1.7%) with AA genotype (Lys109Lys). The distribution of leptin receptor Lys109Arg polymorphism had no significant difference (P > 0.05) between the fatty liver disease patients (95GG, 21GA and 1AA) and the healthy control subjects (49GG, 12GA and 2AA). The abdominal wall fat was significantly thicker in AA genotype subjects (4.1+/-0.4) cm than that in GA (2.8+/-0.6) cm and GG genotype subjects (2.7+/-0.7) cm (F = 5.197, P = 0.006). The serum cholesterol levels in AA genotype subjects (5.1+/-0.4) mmol/L was significantly lower than that in AG (25.5+/-6.9) mmol/L and GG genotype (27.2+/-8.4) mmol/L subjects (F = 8.164, P = 0.005). There were no significant differences in age, body mass index, hip circumference, waist circumference, blood pressure (BP), percentage of body fat, blood protein, triglyceride, HDL and fasting blood glucose between AA, GG and GA genotype subjects.</p><p><b>CONCLUSION</b>Leptin receptor Lys109Arg polymorphism may be involved in the regulation of distribution of abdominal wall fat thickness and cholesterol metabolism. Whether leptin receptor Lys109Arg polymorphism is in any way related to fatty liver disease is still not known.</p>

Research on cytokines gene express of rats alcoholic liver disease affected by tea polyphenol / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic liver damage.</p><p><b>METHOD</b>Rats were divided into 3 groups, in which 2 groups were stomach perfused with alcohol to result in ALD, and 1 group of them stomach perfused with TP simultaneously. Another group was normal control groups (stomach perfused with drinking water). In the end of 12 weeks, the liver specimen of each rat was observed by anglicizing its tissue damage, and all data collected was performed by statistical analysis in quantum and semi-quantum. Meanwhile cytokines gene express of each group is determined.</p><p><b>RESULT</b>In the end of 12 weeks, alcoholic hepatitis appeared in rat liver. Hepatic injury in alcohol group and TP group were found, but could not be found in normal group. Compared with pure alcohol group, alcoholic liver damage mainly showing with steatosis in TP group were slight, in addition showing liver cellular swelling with small area, with less spot and focal necrosis, none bridging necrosis. Steatosis were slight relatively, mega-bubble steatosis were less found. Collagen deposition of TP group were less than those of pure alcohol group. Gene expression of. cytokine have diversity statistically such as IL-3, IL-4, IL-1R2, IL-6R, IL-7R2, IL-3Ra, IL-R1, IL-13, IL-1R1, IL-7R2, EPO-R, LIFR, IL-1R2, IL-5R2, CSF1, CD27, IL-6R.</p><p><b>CONCLUSION</b>TP is able to attenuate alcoholic liver damage. It's mechanism is possibly due to modulating cytokines gene expression of cytokine.</p>

Effect of tea polyphenols on alcoholic liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To reproduce an experimental model of alcoholic liver disease in rats and to investigate the preventive and treatment effects of tea polyphenols on alcoholic liver disease.</p><p><b>METHODS</b>68 male Sprague-Dawley rats were randomly divided into 3 groups: alcohol group (gastrically infused with 56% of ethanol once a day with a dose of 7 g/kg body weight for 4, 12 and 24 weeks), tea polyphenols group (gastric infusion with alcohol same as in the alcohol group and with tea polyphenols at 0.25 g/kg bw) and control group (gastric infusion with normal saline). At the end of 4, 12 and 24 weeks, blood samples were collected and then the rats were sacrificed. Liver samples were obtained for routine histological examination and the degree of hepatic steatosis and alcoholic hepatitis were examined. Blood specimens were used for evaluation of alanine transaminase (ALT) and aspartate aminotransferase (AST).</p><p><b>RESULTS</b>(1) The levels of the two transaminases were elevated with the increase of the duration of ethanol feeding and the difference is significant. TP significantly mitigated the increase of ALT and AST activities induced by the alcohol. (2) Histological changes of the liver injury indicated that piecemeal or focal necrosis of hepatocytes was present in the centrilobular area. As fibrosis advanced, broader septa were formed with central-central and centra-portal bridging necrosis. In the TP infusion group, the severity of the pathological changes was significantly milder.</p><p><b>CONCLUSION</b>The results of this study revealed that TP mitigated the development of alcoholic liver disease, and TP may be a potential drug for treatment of alcoholic liver disease.</p>

Hypoxia inducible factor 1-alpha mRNA expression in alcoholic liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of hypoxia on chronic alcoholic liver disease.</p><p><b>METHODS</b>Twenty four male Sprague-Dawley rats were randomly into two groups. The alcohol group (n=12) was fed 56% (v/v) of ethanol once per day by gastric infusion at 8 g/kg body weight for 24 weeks. The control group (n=12) was gastrically infused with normal saline with the same dose. At the end of 24 weeks, a blood sample was collected for determination of hepatic enzymes and then the rat was killed. Liver specimens were obtained for immunohistochemical staining and frozen at -80 degrees C used for RT-PCR.</p><p><b>RESULTS</b>Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity increased significantly compared to the control group. A significant elevation in the expression of HIF1-alpha in liver of alcohol group was found compared to the control group.</p><p><b>CONCLUSION</b>Hypoxia inducible factor 1-alpha expression was activated by ethanol-induced injury. This information suggested that hypoxia was involved in mechanism of alcoholic liver disease.</p>

Effect of tea polyphenol on liver fibrosis in rats and related mechanism / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of tea polyphenol (TP)'s on liver fibrosis in rats and its possible mechanism.</p><p><b>METHOD</b>Rats were divided into 5 groups, 4 groups of which were stomach perfused with alcohol resulting in alcoholic liver fibrosis, and 3 groups of which were stomach perfused with TP simultaneously. Another group was normal control one. Histological change of rat liver was investigated and quantitative analysis was made in 24 weeks, and rat liver anti-oxidation index and serum endotoxin were determined at the same time.</p><p><b>RESULT</b>Liver fibrosis in TP group was slight, and anti-oxidize index and endotoxin level were markedly improved in comparison with those of alcohol groups.</p><p><b>CONCLUSION</b>Tea polyphenol can protect hepatocytes from fibrosis. Its mechanism is possibly due to cleaning up overfull lipid per-oxidation and reducing the level of endotoxin.</p>

An epidemiological survey of alcoholic liver disease in Zhejiang province / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To describe the brief survey of alcohol intake and the incidence of alcohol liver disease in Zhejiang province.</p><p><b>METHODS</b>18,237 requested persons aged over 18 years were selected by multi-stage stratified cluster sampling in Zhejiang province. Questionnaire about alcohol consumption, hepatic ultrasonic scan and detection of hepatic enzymes and markers of HBV and HCV were carried out. Daily alcohol intake more than 40g (including equal to 40g/d) was essential for the diagnosis of alcoholic liver disease.</p><p><b>RESULTS</b>Among the 18,237 persons (male 12,042, female 6195), the average daily alcohol intake was (17.7 +/- 27.2) g. The incidence of alcoholic liver disease in Zhejiang province was 4.34% (male 6.36%, female 0.36%) in the whole population. Four subtypes were separated as alcoholic cirrhosis, alcoholic fat liver, alcoholic hepatitis and mild alcoholic injury in liver with the corresponding incidence of 0.68%, 0.94%, 1.51% and 1.21% separately.</p><p><b>CONCLUSION</b>Alcoholic liver disease is found to be a common disease in Zhejiang province, indicating an urgent need for the public education on alcohol abuse and the treatment on related health problems</p>

Gene expression of interstitial collagenase MMP-13 in progressive phase of rat liver fibrosis induced by ethanol / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To demonstrate the gene expression of MMP-13 in the progressive phase of ethanol-induced experimental liver fibrosis in rats.</p><p><b>METHODS</b>34 SD rats were randomized into two groups. The rats in experimental group (n=24) were given ethanol (44%, 7g/kg) every day, and the rats in control group (n=10) were given equality normal saline. Liver samples were harvested from experimental rats at the 4th, 12th and 24th weeks respectively. The dynamic expression of MMP-13 mRNA was assayed by semi-quantity reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>In normal rat liver, a faint band of MMP-13 mRNA was observed by RT-PCR (0.24+/-0.41). The gene expression of MMP-13 increased in the livers of rats treated with ethanol for 4 weeks (0.62+/-0.54), but it was not considered statistically, when compared with that in normal rats livers. And the livers from 12-week-treated rats showed a markedly MMP-13 mRNA expression (1.65+/-0.47, t=-4.363, P<0.01). Once the fibrosis became prominent (24 weeks), a faint band of MMP-13 mRNA was observed (0.39+/-0.25).</p><p><b>CONCLUSION</b>MMP-13 participates in the degradation of newly-formed matrix in the early phase of rat liver fibrosis induced by ethanol, but it expresses in a distinct time frame</p>