Prophylactic Pattern Scanning Laser Retinal Photocoagulation for Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats: Preliminary Experimental Results

Research Background and Purpose: The number of diabetic patients is rapidly increasing, making it crucial to find methods to prevent diabetic retinopathy (DR), a leading cause of blindness. We investigated the effects of prophylactic pattern scanning laser retinal photocoagulation on DR development in Spontaneously Diabetic Torii (SDT) fatty rats as a new prevention approach. Methods: Photocoagulation was applied to the right eyes of 8-week-old Spontaneously Diabetic Torii (SDT) fatty rats, with the left eyes serving as untreated controls. Electroretinography at 9 and 39 weeks of age and pathological examinations, including immunohistochemistry for vascular endothelial growth factor and glial fibrillary acidic protein at 24 and 40 weeks of age, were performed on both eyes. Results: There were no significant differences in amplitude and prolongation of the OP waves between the right and left eyes in SDT fatty rats at 39 weeks of age. Similarly, no significant differences in pathology and immunohistochemistry were observed between the right and left eyes in SDT fatty rats at 24 and 40 weeks of age. Conclusion: Prophylactic pattern scanning retinal laser photocoagulation did not affect the development of diabetic retinopathy in SDT fatty rats.

Experimental models of non-alcoholic fatty liver disease in rats

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the Western world,and it persists at a high prevalence.NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings,ranging from simple fatty liver through non-alcoholic steatohepatitis(NASH)to fibrosis and ultimately cirrhosis,which may progress to hepatocellular carcinoma.The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance.Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models.The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages.Within the past several years,great emphasis has been placed on the development of an appropriate model for human NASH.This paper reviews the widely used experimental models of NAFLD in rats.We discuss nutritional,genetic and combined models of NAFLD and their pros and cons.The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies.Considering the legislative,ethical,economical and health factors of NAFLD,animal models are essential tools for the research of this disease.

Therapeutic effects of sericin on diabetic keratopathy in Otsuka Long-Evans Tokushima Fatty rats

An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.

Danhong Huayu Koufuye combined with metformin attenuated diabetic retinopathy in Zucker diabetic fatty rats

AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

AIM： To evaluate the possible role of Tribble 3 （TRB3） in a rat model of non-alcoholic fatty liver disease （NAFLD） and its signal transduction mechanism.METHODS： Thirty Sprague-Dawley rats were randomized into three groups： normal control group, non-alcoholic fatty liver group A （fed on a high-fat diet for 8 wk） and group B （fed on a high-fat diet for 16 wk）. To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and evaluated; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 mRNA, and Western blotting analysis was done to determine the expression levels of protein kinase B （Akt） and phosphorylated protein kinase B （p-Akt-Thr308, p-Akt-Ser473）.RESULTS： Hepatic steatosis was evident in both NAFLD groups： mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis.Moderate to severe hepatic steatosis occurred in group B, mainly as severe steatosis. The expression level of TRB3 mRNA in group B was significantly higher than in the control group （122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002） and group A （122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001）. There was no significant difference in the expression levels of Akt （1.03 ± 0.53 vs 1.12 ± 0.77,P = 0.729） and p-Akt-Thr308 （0.82 ± 0.45 vs 0.92 ± 0.38, P = 0.592） between group A and the control group. The expression level of Akt and p-Akt-Thr308 in group B was significantly lower than in group A （Akt 0.41 ± 0.16 vs 1.12 ± 0.77, P = 0.008; p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45, P = 0.036） and the control group （Akt 0.41 ± 0.16 vs 1.03 ± 0.53, P = 0.018;p-Akt-Thr308 0.47 ± 0.19 vs 0.92 ± 0.38, P = 0.010）.The expression level of p-Akt-Ser473 in group A was significantly higher than in group B （1.48 ± 0.50 vs 0.81± 0.39, P = 0.041） as well as the control group （1.48 ± 0.50 vs 0.45 ± 0.26, P = 0.003）.CONCLUSION： TRB3 blocks insulin signaling by inhibiting Akt activation, which contributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.

Polygonatum sibiricum polysaccharides protect against obesity and non-alcoholic fatty liver disease in rats fed a high-fat diet

Polygonatum sibiricum is a traditional medicinal and dietary plant of the family Liliaceae. The main functional macromolecules of P. sibiricum are polysaccharides, which function in antioxidation and regulating immunity. Previous studies have shown that insulin resistance(IR), oxidative stress, and inflammation are important factors in the induction of lipid metabolic diseases such as obesity. Therefore, in this study, we established a high-fat diet-induced rat model of obesity and nonalcoholic fatty liver disease(NAFLD) to explore the potential protective effect of P. sibiricum polysaccharides(PSPs) and the mechanisms behind it. After 4 weeks of high-fat diet feeding to induce obesity, the rats were treated with different doses of PSP solution or distilled water for 6 weeks. Compared with untreated obese rats, PSP-treated obese rats showed a decrease in body weight, serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, hepatic aspartate aminotransferase and alanine aminotransferase activity, hepatic malondialdehyde content, and hepatic levels of the pro-inflammatory factors tumor necrosis factor-α, interleukin-1β, and interleukin-6, as well as increased serum high-density lipoprotein cholesterol levels and hepatic superoxide dismutase, catalase, and glutathione peroxidase activity. Pathological analysis and immunoblotting of the liver tissues indicated that mechanistically, PSPs reduced obesity and NAFLD in rats by upregulating insulin receptor expression, increasing adenosine monophosphate-activated protein kinase phosphorylation, and downregulating sterol regulatory element-binding protein 2 and low-density lipoprotein receptor expression, thus promoting lipid metabolism, decreasing body weight, and reducing inflammation and oxidative stress caused by lipid accumulation. Based on these results, PSPs may have the potential to reduce obesity and NAFLD associated with a high-fat diet.

Ocular findings in Zucker Diabetic Fatty rats emphasize the key role of neuroglia degeneration in diabetic retinopathy pathophysiology

Diabetes mellitus is a leading cause of acquired vision loss and one of the world＇s fastest growing chronic diseases. Diabetic retinopathy （DR）, a specific complication of chronic hyperglycemia, is the leading cause of acquired vision loss worldwide in middle-aged and there- fore economically active people that also increases the medical and economic burden on the society （Klein, 2007）.

Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

AIM:To investigate the histological features of the liver in spontaneously diabetic Torii(SDT) fatty rats compared with age-matched Sprague-Dawley(SD) rats.METHODS:Female SDT Leprfa(SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters,such as serum glucose,triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the nonfasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis,inflammation,and fibrosis was examined in the liver.RESULTS:SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose,TG,and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically,severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age,and fibrosis started to occur at 32 wk of age. Furthermore,Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis,inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats,and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION:Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity.

Soybean Flour Improves Fatty Acid Profile and Decreases Hepatic Triglyceride Deposition in Rats Fed with Normocaloric and Hypercaloric Diet

This study investigated the effects of replacing casein with soy flour on the fatty acids profile and triglycerides metabolism in the liver of rats that were previously fed with normocaloric and hypercaloric diets based on casein. Wistar male rats were used;one group was fed with control diet (AIN-93) and another with hypercaloric diet (AIN-93 with 34.15% sucrose, 42% fat calories) for 9 weeks. Each group was then divided into two subgroups and casein was replaced with soybean in one of them, obtaining CC (control casein), CS (control soy), HC (hypercaloric casein) and HS (hypercaloric soy), which were fed for 6 weeks. We measured triglycerides in serum, and triglycerides, total lipids, fatty acids profile, the expression of apolipoprotein B (Apo B), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element-binding protein 1c (SREBP-1c), mitochondrial glycerol-3-phosphate acyltransferase (mGPAT), diacylglycerol acyltransferase 2 (DGAT-2), carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator-activated receptors alpha (PPARα) in liver. Histological studies were also performed. When comparing HS vs. HC, a positive effect of soybean flour on hepatic triglycerides deposits was found, possibly through the reduction in DGAT-2 expression (P < 0.01) and the increase in Apo B (P < 0.001) expression. Soybean flour also decreased fat deposits in control diets when compared with casein, decreasing the DGAT-2 (P < 0.001) expression and increasing Apo B (P < 0.001), CPT-1 (P < 0.05) and PPARα (P < 0.01) expressions. Both soy diet subgroups increased unsaturated fatty acids respect to casein diets (P < 0.01). Hepatocytes showed few lipid droplets in HS, whereas a fat deposit in HC was observed. These results suggest that replacing casein with soybean flour in normocaloric and hypercaloric diets reduces triglycerides and improves fatty acids profile in rat liver.

Effects of common prebiotics on iron status and production of colonic short-chain fatty acids in anemic rats

Prebiotics may enhance iron absorption,and one plausible mechanism involves the production of shortchain fatty acids(SCFA)in the colon by intestinal microflora.The objectives of this study were to determine the effects of common commercially-available prebiotics including fructooligosaccharide(FOS),inulin,FOS-inulin mixture,galactooligosaccharide(GOS),and lactulose on the iron status of anemic rats,and to monitor changes in the production of colonic SCFA.Anemic Sprague-Dawley rats receiving a lowiron diet(12μg Fe/g diet)were supplemented with or without prebiotics(5%m/V in drinking water)for 5 weeks.Hemoglobin concentration in rats supplemented with GOS after 3 weeks(4.3 g/dL)was significantly higher than rats without supplementation(3.7 g/dL),while FOS also significantly increased hemoglobin concentration after 4 weeks(4.1 g/dL vs.3.7 g/dL).All other prebiotics showed no effects.Anemic rats showed lower overall SCFA production in the colon than normal rats,and only FOS signifi cantly increased the production of the three main SCFA(acetic acid,propionic acid and isobutyric acid)identifi ed in anemic rats,with other prebiotics showing no noticeable trends.Our results suggest that GOS and FOS may slightly improve iron status of anemic rats,but the role of SCFA in the colon is not clear.

Bitter Melon Powder Protects against Obesity-associated Fatty Liver Disease by Improving Colonic Microenvironment in Rats with High-fat Diet-induced Obesity

This study explored how bitter melon powder （BMP） alters the colonic microenvironment during the development of obesity-associated fatty liver in rats. We observed that BMP effectively inhibited the body weight gain and lipid accumulation in the liver, ameliorated glucose intolerance, and increased the colon weight after an 8-week treatment compared to that in the high-fat diet （HFD） group. BMP significantly decreased fecal water toxicity towards HT-29 cells, as revealed by the cell counting kit （CCK）-8 assay results, and the mRNA expression of Toll-like receptor 4 （TLR4） in colon mucosa. Additionally, gut permeability in the BMP group was restored to normal levels. Finally, BMP alleviated the inflammatory state of the rat colon mucosa and liver tissues as well as the systemic inflammation.

Bioactive Fatty Acids Reduce Development of Gastric Cancer Following Duodenogastric Reflux in Rats

Background: Bioactive fatty acids such as the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the modified fatty acid analogue, tetradecylthioacetic acid (TTA), are known to influence inflammatory processes in the body. Our aim was to investigate if diets containing fish oil (FO) enriched with bioactive fatty acids could affect inflammation and development of glandular stomach carcinogenesis in a duodenogastric reflux (DGR) animal model. We also wanted to evaluate if a high-fat diet might increase the risk of developing gastric cancer compared to a low-fat diet. Methods: 185 rats operated on with a gastroenterostomy were randomly allocated to 5 different treatment groups given: low-fat, high-fat, high-fat + FO, high-fat + TTA or high-fat + FO + TTA. The stomachs were removed after 50 weeks and examined by light microscopy with hematoxylin and eosin staining (HE). Immunohistochemical staining against COX-2, PCNA and p53 was performed when adenocarcinomas were found. The plasma fatty acid profile was determined. Results: Adenocarcinomas developed in 21% of animals fed the low-fat diet, 35% in the high-fat group, 16% in the high-fat + TTA group, 21% in the high-fat + FO group and 8.6% in the high-fat + FO + TTA treatment group. COX-2 and PCNA were positive whereas p53 was negative in the majority of the samples. The anti-inflammatory fatty acid index increased after treatment with FO and in combination with FO and TTA. Conclusion: FO and TTA in combination with a high-fat diet significantly lower the risk of developing adenocarcinomas in rats subjected to duodenogastric reflux. This is most likely due to a selective modulation of inflammation.

Effect of Cholesterol Enriched or Fatty-Acid Diets on Cholesterol and Lipid Levels in Young Wistar Rats

Nutritional intake is a fundamental determinant of health. It is well known that cholesterol rich diets can induce several pathological conditions but detailed mechanism underlying these remains unknown. Wistar rats, an animal strain widely used in the research have been employed to study the effects of dietary interventions due to their metabolic characteristics, which are closer to the human compared to mice. The effect of some components of the western diet, combined with cholesterol in the lipid profile have been studied, but the impact of only cholesterol or fatty-acid diets in such a profile has not been yet characterized. Here we measured the effect of 6 or 16 weeks of dietary intervention with cholesterol enriched diet (CED) or fatty-acid diet (FAD) on cholesterol, triglyceride levels, high density lipoproteins (HDL) and low density lipoproteins (LDL). We observed significant differences in body weight only in animals treated with CED or FAD from Week 9 onwards as compared to animals fed the control diet. There were no differences between animals fed with CED or FAD in cholesterol levels at any time point nevertheless, triglyceride levels were significantly increased as compared to control diet in animals under both diets at early time points. Finally, both CED and FAD induced a decrease in HDL as compared to control levels in treatments of more than 6 weeks, whereas LDL transiently increased in animals treated with FAD from 10 to 12 weeks, but after this period LDL levels returned to baseline, suggesting that young rats have a compensatory effect at least for the period of time analyzed here. Here we provide a temporal course on lipid profile of cholesterol, triglycerides, HDL and LDH in Wistar rats treated with CED and FAD diet that can be useful as reference for future studies.

OTSUKA-LONG-EVANS-TOKUSHIMA FATTY糖尿病大鼠周围神经的结构蛋白改变

为了解 Otsuka-Long-Evans-Tokushima Fatty( OLETF)糖尿病大鼠周围神经的结构蛋白改变 ,使用 OL ETF大鼠 10只/L ong-Evans-Tokushima-Otsuka( LETO)对照大鼠 6只 ,于糖尿病发病后 6个月取坐骨神经 ,制成冰冻切片和单纤维贴片 ,进行神经结构蛋白的免疫组织化学染色。在光镜下观察到 OLETF大鼠周围神经部分区域有结构异常。轴索结构中 ,Ranvier结区的钠离子通道蛋白密度降低并向结旁区移位 ,近结旁段的钾离子通道蛋白 ( Kv1.1)向 Ranvier结区和节间段弥散 ,神经丝着色浅淡且不均匀。髓鞘结构中 ,结旁段的髓鞘相关糖蛋白着色不均匀并向节间段弥散 ,致密髓鞘层的髓鞘碱性蛋白和 Schwann细胞表面的半乳糖脑苷脂基本正常。上述结果提示 Ranvier结区的轴膜和结旁段的髓鞘是 OL

Effects of cold preservation and warm reperfusion on rat fatty liver

INTRODUCTIONAlthough liver transplantation for irreversible liverdiseases is increasingly prevalent worldwide,patientdie while waiting for donors because of organshortages.One important problem commonlyencountered is that fatty livers often affect theoutcome of liver transplantation.It is reported thatthe incidence of abnormal fatty livers in autopsiesafter accidental death ranged from 15% to 24%.Since fatty livers may result in a primarynonfunction (PNF)liver graft,which contributes

Effect of nuclear factor-κB and angiotensin Ⅱ receptor type 1 on the pathogenesis of rat non-alcoholic fatty liver disease

AIM: To investigate the roles of nuclear factor(NF)-κB and angiotensin Ⅱ receptor type 1(AT1R) in the pathogenesis of non-alcoholic fatty liver disease(NAFLD).METHODS: Forty-two healthy adult male SpragueDawley rats were randomly divided into three groups:the control group(normal diet), the model group,and the intervention group(10 wk of a high-fat diet feeding, followed by an intraperitoneal injection of PDTC); 6 rats in each group were sacrificed at 6, 10,and 14 wk. After sacrifice, liver tissue was taken,paraffin sections of liver tissue specimens were prepared, hematoxylin and eosin(HE) staining was performed, and pathological changes in liver tissue(i.e., liver fibrosis) were observed by light microscopy.NF-κB expression in liver tissue was detected by immunohistochemistry, and the expression of AT1 R in the liver tissue was detected by reverse transcriptionpolymerase chain reaction(RT-PCR). The data are expressed as mean ± SD. A two-sample t test was used to compare the control group and the model group at different time points, paired t tests were used to compare the differences between the intervention group and the model group, and analysis of variance was used to compare the model group with the control group. Homogeneity of variance was analyzed with single factor analysis of variance. H variance analysis was used to compare the variance. P < 0.05 wasconsidered statistically significant.RESULTS: The NAFLD model was successful after 6wk and 10 wk. Liver fibrosis was found in four rats in the model group, but in only one rat in the intervention group at 14 wk. Liver steatosis, inflammation, and fibrosis were gradually increased throughout the model. In the intervention group, the body mass,rat liver index, serum lipid, and transaminase levels were not increased compared to the model group.In the model group, the degree of liver steatosis was increased at 6, 10, and 14 wk, and was significantly higher than in the control group(P < 0.01). In the model group, different degrees of liver cell necrosis were visible and small leaves, punctated inflammation,focal necrosis, and obvious ballooning degeneration were observed. Partial necrosis and confluent necrosis were observed. In the model group, liver inflammatory activity scores at 6, 10, and 14 wk were higher than in the control group(P < 0.01). Active inflammation in liver tissue in the intervention group was lower than in the model group(P < 0.05). HE staining showed liver fibrosis only at 14 wk in 4/6 rats in the model group and in 1/6 rats in the intervention group. NF-κB positive cells were stained yellow or ensemble yellow,and NF-κB was localized in the cytoplasm and/or nucleus. The model group showed NF-κB activation at6, 10, and 14 wk in liver cells; at the same time points,there were statistically significant differences in the control group(P < 0.01). Over time, NF-κB expression increased; this was statistically lower(P < 0.05) at14 weeks in the intervention group compared to the model group, but significantly increased(P < 0.05)compared with the control group; RT-PCR showed that AT1 R mRNA expression increased gradually in the model group; at 14 wk, the expression was significantly different compared with expression at 10 weeks as well as at 6 weeks(P < 0.05). In the model group, AT1 R mRNA expression was significantly higher than at the same time point in the control group(P <0.01).CONCLUSION: With increasing severity of NAFLD,NF-κB activity is enhanced, and the inhibition of NF-κB activity may reduce AT1 R mRNA expression in NAFLD.

Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to regeneration.RESULTS The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P < 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P < 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P < 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P < 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P < 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.

Alterations of attention and impulsivity in the rat following a transgenerational decrease in dietary omega-3 fatty acids

Polyunsaturated fatty acids(PUFAs),particularly the omega-3 PUFAs,are thought to be involved in neuronal processes,to play a role in neurodevelopmental disorders and to be important for the integrity of central nervous system functioning.The present study investigated the effects of nutritional omega-3 PUFAs on attentional functions and impulsive behavior in Wistar rats.For this purpose,female Wistar rats were fed an omega-3 deficient diet over several generations,and the dams of the seventh generation were randomly assigned to two diet groups and fed an omega-3 deficient or an omega-3 sufficient diet.In addition,a group of previously untreated dams was fed an omega-3 sufficient diet.The male offspring of these three diet groups were tested using an established paradigm for the assessment of attention and impulsive behavior,i.e.a modified version of the five-choice-serial-reaction-time task(5CSRTT).The present data show that the deficiency of omega-3 PUFAs over generations led to substantial changes in attentional processes and impulsive behaviors.The impairments associated with an omega-3 deficiency were partly corrected by treatment with the omega-3 sufficient diet in the last generation of the omega-3 deficient group which showed substantial improvements in attention parameters.While there were no significant effects of dietary modifications on psychomotor activity levels,there was some evidence for changes in impulsive behavior.In conclusion,transgenerational dietary changes in the availability of omega-3 PUFAs led to changes in attentional processes and impulsive behavior in rats,supporting the hypothesis that omega-3 PUFAs play a role in cognitive and behavioral processes.The present findings offer a promising approach in the investigation of the role of omega-3 PUFAs in a variety of cognitive and behavioral domains.

Chemical Composition of the Fatty Oil from Fructus Broussonetiae and Its Effects on Rat Plasma Lipids and Adipose Tissue

Context: Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Its fruits (Fructus Broussonetiae) have been commonly used as an important tonic for the treatment of age-related disorders with long history;recent research has proved that it contains 32% to 35% fixed oils. The fixed oil is composed mainly of unsaturated fatty acids, including linoleic acid, methyl palmitate, oleic acid and linoleic acid ester. Objective: To investigate the chemistry of the fatty oil from Fructus Broussonetiae (FOFB) and its effects on plasma lipids. Methods: The chemical composition of FOFB was examined and identified by GC-MS. Thirty male Wistar rats fed diet containing FOFB and cholesterol were studied for 28 days. The effect of dietary FOFB on plasma lipids and adipose tissue was tested. Results: Twelve compounds of FOFB were examined and identified, the major components of fatty oil, 8,11-octadecadienoic acid (83.75%), palmitic acid (10.22%), octadecadienoic acid (2.97%) and 9-octadecenoic acid (1.69%) were found. FOFB significantly exhibited the activities of decreasing the rat adipose tissue weight, triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) concentrations while the rat body weight remained unchanged. Discussion: FOFB contained a large amount of PUFA which had the effect on reducing plasma lipids and adipose.

EXPERIMENTAL STUDY ON PRESERVATION OF RAT FATTY LIVER

OBJECTIVE: To investigate the effects of cold preservation on rat fatty liver. METHODS: We observed the changes of portal perfusion pressure, endothelin-1, enzymes release in the effluent and mortality of sinusoid lining cell after 0h, 6h, or 12h preservation respectively and a subsequent 30 min reperfusion in rat fatty liver groups and control groups by using isolated perfused rat liver model. And we compared fatty liver groups with control groups by these indices. RESULTS: There was no obvious difference between mildly fatty liver group and control group after long time (12h) preservation, between moderately fatty liver group and control group after short time (6h) preservation, between severely fatty liver group and control group without preservation (0h), while preservation reperfusion injury was more severe in moderately fatty liver group than in control group after long time (12h) preservation and in severely fatty liver group than in control group after short time (6h) preservation. CONCLUSIONS: The authors suggested that a mildly fatty liver donor could be used in the same way as nonfatty liver and a moderately fatty liver donor could be used depending on the time of preservation and the balance of the emergent needs of recipient and donor organ supply, while severely fatty liver donor should be discarded without hesitation.