Antihyperglycemic effect of stem bark powder from paper mulberry (Broussonetia kazinoki Sieb.) in type 2 diabetic Otsuka Long-Evans Tokushima fatty rats

The effect of stem bark powder from paper mulberry (PMSB) on serum glucose, insulin, fructosamine, and lipid concentrations, as well as enzyme activities that serve as liver injury markers, was investigated in genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Both nondiabetic Long-Evans Tokushima Otsuka (LETO) rats and diabetic OLETF rats (30 weeks old) were fed a semisynthetic diet with or without 50 g/kg PMSB for 8 weeks and then compared. The OLETF control rats showed a high amount of daily water intake in comparison to those in the LETO group. The concentrations of glucose, fructosamine, total lipid, triglyceride, total cholesterol, and high-density lipoprotein-cholesterol and the activities of aspartate aminotransferase and alanine aminotransferase (ALT) in serum were higher in the OLETF control rats than those in the LETO control rats. However, PMSB ingestion decreased the serum levels of glucose, fructosamine, triglyceride, and total cholesterol and the activity of ALT in the OLETF rats, but not in the LETO rats. The concentration of serum insulin was also significantly increased by PMSB consumption in the OLETF rats compared to the OLETF control rats. These results suggest that PMSB might have an antihyperglycemic effect in the OLETF rat and that the increased blood insulin level would be an important regulatory factor for improving hyperglycemia in the current animal model.     

Replacing white rice with pre-germinated brown rice mildly ameliorates hyperglycemia and imbalance of adipocytokine levels in type 2 diabetes model rats

Pre-germinated brown rice (PR) has been developed industrially in order to enhance the nutritional functions of its source material, brown rice (BR). The present study was aimed at clarifying the effect of PR on the type 2 diabetes mellitus. We employed Otsuka Long-Evans Tokushima Fatty (OLETF) rats as a model of type-2 diabetes mellitus. OLETF rats were fed on either PR or white rice (WR) from the age of 4 to 35 wk. Age-matched male Long-Evans Tokushima Otsuka (LETO) rats as a non-diabetic control were also fed on WR. The HbA(1c) level in OLETF rats was significantly higher than that in LETO rats. However, the level was lower in PR-fed OLETF rats than in WR-fed OLETF rats. The plasma concentrations of TNF-α and PAI-1 in OLETF rats were higher than those in LETO rats. However, both elevated levels were decreased by the PR-feeding, but not by the WR-feeding. On the other hand, the plasma adiponectin concentration in OLETF rats was lower than that in LETO rats. The decrease in adiponectin level of OLETF rats was ameliorated by PR-feeding. The size of adipocytes in PR-fed OLETF rats was smaller than that in WR-fed OLETF rats. In summary, intake of PR instead of WR ameliorates both insulin resistance and imbalance of the levels of plasma adipocytokines leading to diabetic complications.     

罗格列酮对OLETF大鼠肺组织转化生长因子β1及其信号转导分子的影响

目的探讨罗格列酮对自发性糖尿病OLETF(Otsuka Long-Evans Tokushima Fatty)大鼠肺组织纤维化的影响及其机制。方法 30周龄雄性OLETF大鼠16只,随机分为糖尿病组(DM组)和罗格列酮组(RGT组,予罗格列酮3mg·kg-1·d-1灌胃12周),对照组为LETO(Long Evans Tokushima Otsuka)大鼠8只。HE、Masson染色观察各组大鼠肺组织结构及其胶原沉积变化,免疫印迹(Westernblotting)方法检测肺组织Smad3、Smad7和Ⅲ型胶原表达,ELISA检测肺组织转化生长因子β(1transforming growth factor-β1,TGF-β1)的表达。结果与对照组大鼠相比,DM组大鼠肺组织TGF-β1、Smad3和Ⅲ型胶原表达增加,Smad7表达减少,差异均有统计学意义(P<0.05),肺组织胶原沉积增加,呈纤维化趋势;罗格列酮治疗可使RGT组大鼠上述指标逆转。结论罗格列酮对OLETF大鼠肺组织有抗纤维化作用,可能通过下调TGF-β1/Smad信号转导通路发挥作用。     

The diurnal rhythm of energy expenditure differs between obese and glucose-intolerant rats and streptozotocin-induced diabetic rats

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of noninsulin-dependent diabetes mellitus (NIDDM) with mild obesity. Changes in carcass composition and in the daily profile of energy expenditure were examined before and after manifestation of diabetes (8 and 24 wk, respectively), and compared with the normal control Long Evans Tokushima (LETO) rats and streptozotocin (STZ)-induced diabetic LETO rats. OLETF rats had greater body weights than LETO rats and significantly greater absolute and relative fat weights. A diurnal rhythm of energy expenditure associated with two peaks was observed in LETO rats, but the two peaks were not apparent in OLETF rats at 24 wk of age. A diurnal rhythm associated with one peak was observed in STZ-induced diabetic LETO rats. Energy derived from fat constituted this peak; the pattern of the daily energy expenditure was significantly different from that of either nontreated LETO or OLETF rats at 24 wk of age. NIDDM in OLETF rats at 24 wk of age has only a small role in modification of the diurnal rhythm of energy expenditure, whereas STZ-induced diabetes significantly affected the rhythm.     

Taurine alters respiratory gas exchange and nutrient metabolism in type 2 diabetic rats

OBJECTIVE: To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. RESEARCH METHODS AND PROCEDURES: Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine-supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long-Evans Tokushima Otsuka) was used as the age-matched normal control. RESULTS: The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. DISCUSSION: Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles.     

Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes

BACKGROUND: Taurine, a potent antioxidant, has been reported to improve streptozotocin-induced diabetes mellitus, in which the development of diabetes results from an attack by oxygen free radicals on pancreatic beta cells. However, taurine also increases the excretion of cholesterol via conversion to bile acid and would be expected to improve insulin resistance. OBJECTIVE: The effects of taurine on insulin sensitivity were examined in a model rat of insulin resistance and type 2 diabetes-the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. DESIGN: Male OLETF rats were divided into 2 groups at the age of 16 wk: a taurine-supplemented group and an unsupplemented group. As a nondiabetic control, Long-Evans-Tokushima-Otsuka rats were used. An oral-glucose-tolerance test and hyperinsulinemic euglycemic clamp were performed at the ages of 23 and 25 wk. RESULTS: The OLETF rats had hyperglycemia and insulin resistance and they had a greater accumulation of abdominal fat than did control rats. Abdominal fat accumulation, hyperglycemia, and insulin resistance were significantly lower in the taurine-supplemented group than in the unsupplemented group. Serum and liver concentrations of triacylglycerol and cholesterol were significantly higher in the OLETF rats than in the control rats and were significantly lower in the taurine-supplemented group than in the unsupplemented group, presumably because of the increased secretion of cholesterol into bile acid. Taurine-supplemented rats also showed higher nitric oxide secretion, evidenced by increased urinary excretion of nitrite. CONCLUSION: Taurine effectively improves metabolism in OLETF rats by decreasing serum cholesterol and triacylglycerol, presumably via increased secretion of cholesterol into bile acid and decreased production of cholesterol because of increased nitric oxide production.     

S-adenosyl-L-methionine increases skeletal muscle mitochondrial DNA density and whole body insulin sensitivity in OLETF rats

Both mitochondrial dysfunction and alterations in mitochondrial DNA (mtDNA) are implicated in type 2 diabetes mellitus and insulin resistance. Evidence also suggests that metabolism of S-adenosyl-L-methionine (SAM), the universal methyl donor for biological methylation, is associated with mitochondrial dysfunction and insulin resistance. We investigated the effect of SAM on mtDNA density and insulin sensitivity using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of type 2 diabetes mellitus and insulin resistance. To determine the short-term effect on mtDNA density, SAM (15 mg.kg-1.d-1) was administered intraperitoneally for 7 d to 6 male, 57-wk-old OLETF rats and 6 Long-Evans Tokushima Otsuka (LETO) rats of the same age as a nondiabetic control. To determine the long-term effect, the same dose of SAM was administered daily to 5 male, 6-wk-old OLETF rats until the age of 25 wk; 7 control OLETF rats received vehicle and 7 LETO rats were untreated. Skeletal muscle mtDNA density was measured by either competitive or multiplex PCR and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. SAM treatment for 1 wk increased skeletal muscle mtDNA density of both OLETF and LETO rats. The long-term SAM treatment significantly reduced body weight gain as well as increased skeletal muscle mtDNA density and whole body insulin sensitivity in OLETF rats compared with their vehicle-treated controls. Furthermore, in all 3 groups, skeletal muscle mtDNA density correlated with insulin sensitivity (r=0.752, P<0.001). In conclusion, SAM treatment increased mtDNA density in the skeletal muscle, improved whole body insulin sensitivity, and prevented body weight gain in OLETF rats.     

The 10trans, 12cis isomer of conjugated linoleic acid promotes energy metabolism in OLETF rats

OBJECTIVE: We investigated the effect of conjugated linoleic acid (CLA) on energy metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: In experiment 1, male OLETF rats were fed either control diet, 10% safflower oil or CLA diet, 9% safflower oil plus 1% CLA for 4 wk. In experiment 2, male OLETF rats were fed either 9c,11t-CLA diet, 9% safflower oil plus 1% 9c,11t-CLA-rich oil or 10t,12c-CLA diet, 9% safflower oil plus 1% 10t,12c-CLA-rich oil for 10 d. RESULTS: In experiment 1, after 4 wk of feeding, serum and hepatic triacylglycerol concentrations in the CLA group were decreased significantly as compared with the control group. The CLA diet increased oxygen consumption and energy expenditure as compared with the control diet in OLETF rats. In experiment 2, a significant reduction of serum and hepatic triacylglycerol concentrations was seen in the 10t,12c-CLA group as opposed to the 9c,11t-CLA group. Oxygen consumption and energy expenditure were significantly higher in the 10t,12c-CLA group than in the 9c,11t-CLA group. CONCLUSIONS: These results demonstrated that the hypolipidemic effect and the enhancement of energy metabolism by CLA can be attributed to the effect of the 10t,12c-CLA isomer.     

Health implications of fructose consumption: A review of recent data

Background

An increase in the intestinal permeability is considered to be associated with the inflammatory tone and development in the obesity and diabetes, however, the pathogenesis of the increase in the intestinal permeability is poorly understood. The present study was performed to determine the influence of obesity itself as well as dietary fat on the increase in intestinal permeability.

Methods

An obese rat strain, Otsuka Long Evans Tokushima Fatty (OLETF), and the lean counter strain, Long Evans Tokushima Otsuka (LETO), were fed standard or high fat diets for 16 weeks. Glucose tolerance, intestinal permeability, intestinal tight junction (TJ) proteins expression, plasma bile acids concentration were evaluated. In addition, the effects of rat bile juice and dietary fat, possible mediators of the increase in the intestinal permeability in the obesity, on TJ permeability were explored in human intestinal Caco-2 cells.

Results

The OLETF rats showed higher glucose intolerance than did the LETO rats, which became more marked with the prolonged feeding of the high fat diet. Intestinal permeability in the OLETF rats evaluated by the urinary excretion of intestinal permeability markers (Cr-EDTA and phenolsulfonphthalein) was comparable to that in the LETO rats. Feeding the high fat diet increased intestinal permeability in both the OLETF and LETO rats, and the increases correlated with decreases in TJ proteins (claudin-1, claudin-3, occludin and junctional adhesion molecule-1) expression in the small, but not in the large intestine (cecum or colon). The plasma bile acids concentration was higher in rats fed the high fat diet. Exposure to bile juice and the fat emulsion increased TJ permeability with concomitant reductions in TJ protein expression (claudin-1, claudin-3, and junctional adhesion molecule-1) in the Caco-2 cell monolayers.

Conclusion

Excessive dietary fat and/or increased levels of luminal bile juice, but not genetic obesity, are responsible for the increase in small intestinal permeability resulting from the suppression of TJ protein expression.     

Dietary effect of pomegranate seed oil rich in 9cis, 11trans, 13cis conjugated linolenic acid on lipid metabolism in obese,hyperlipidemic OLETF Rats

Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9 cis, 11 trans, 13 cis -conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid β-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.     

Bitter melon malt vinegar increases daily energy turnover in rats

Vinegar is generally believed to be good for health. A mash consisting of 35% ethanolic extract from bitter melon malt vinegar-water (8:50:42) was subjected to further acetate fermentation and the resulting vinegar was converted to dried vinegar powder by spray drying after adsorption on dextrin, which was mixed with a commercial rat chow (CRF-1) in the ratio of 1:19 so as to prepare an experimental diet. Male 12-wk old rats of LETO and OLETF strains were fed this experimental diet in parallel with CRF-1 (control) and examined for respiratory quotient (RQ) and blood or plasma parameters associated with diabetes mellitus. Administration of the experimental diet increased daily food intake as well as daily energy expenditure in both strains. RQ significantly lessened in the vinegar diet-fed group of LETO strain, which was reflected not only in the increased energy consumption from fat but also in the decreased energy consumption from carbohydrate, while no significant difference was observed between both dietary groups of OLETF strain in this respect. The profiles of diurnal energy expenditure in both dietary groups of LETO strain exerted two peaks before lights-on and lights-off. Nevertheless, there was a clear difference between both dietary groups of OLETF strain: interestingly the reproduction of the two peaks became conspicuous in the vinegar diet-fed group despite the lack of such peaks in the control. As a consequence of blood or plasma inspection, it turned out that there was no change in HbA1c but a significant increase in plasma cholesterol in the vinegar diet-fed OLETF rats. From these results, a long-term administration of bitter melon malt vinegar can be expected to suppress a lowering of energy turnover inherent with aging and thereby improve anorexia rather than to bring about a preventive effect against the manifestation of NIDDM.     

Inhibitory effects of soy isoflavones on cardiovascular collagen accumulation in rats

Oxidative stress is a major cause of cardiovascular tissue fibrosis. We evaluated the effects of daily doses of soy isoflavones, genistein and daidzein on cardiovascular tissue fibrosis in Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats and Long-Evans Tokushima Otsuka (LETO) non-diabetic rats as a severe or mild oxidative stress model, respectively. Glucose and lipid metabolisms did not improve with genistein or daidzein treatment. However, genistein decreased hydroxyproline concentrations in the heart. Hydroxyproline reductions as a result of genistein were mildly stronger than those of daidzein. Thus, genistein significantly suppressed the progression of myocardial fibrosis in LETO rats despite the insignificant changes in OLETF rats. Although a daily dosage of isoflavone was not sufficient to prevent tissue fibrosis under marked oxidative stress in the early stage of diabetes, isoflavones might promise significant clinical benefits by reducing oxidative stress in the heart during aging.     

精氨酸、谷氨酰胺双肽强化肠外营养对创伤后肠屏障功能和机体免疫功能的影响

目的 探讨精氨酸、谷氨酰胺双肽强化肠外营养（PN）对创伤后肠屏障功能和机体免疫功能的影响.方法 将50只雄性Wister大鼠创伤后随机分为对照组、传统PN组（PN）、精氨酸强化PN组（PN-A）、谷氨酰胺双肽强化PN组（PN-G）和精氨酸-谷氨酰胺双肽强化PN组（PN-A-G）5组,每组10只.经7天营养支持后分别检测体重、空肠黏膜厚度、绒毛高度、结肠黏膜厚度、肠系膜淋巴结细菌移位率、周围血淋巴细胞增殖能力.结果 （1）手术前5组大鼠的平均体重差异无显著性,术后7天接受PN支持的4组大鼠体重均较术前降低,而对照组则有增加,其中PN组和PN-A组较含有谷氨酰胺强化的两组体重降低更为显著（P＜0.05）.（2）经过7天PN支持后,PN组和PN-A组空肠和结肠的黏膜厚度及空肠绒毛高度较对照组明显降低（P＜0.05）;PN-G组和PN-A-G组则与对照组相似.（3）术后第8天,各组细菌移位阳性率以PN组最高,PN-A组次之,PN-G组和PN-A-G组与对照组间差异无显著性.（4）治疗前各组大鼠周围血淋巴细胞在有丝分裂原ConA和PHA刺激后增殖率相似;经7天营养支持后,接受PN支持的PN组和PN-A组大鼠淋巴细胞增殖率明显低于对照组（P＜0.05）,而PN-G组和PN-A-G组与对照组比较差异无显著性（P＞0.05）,除对照组外各组均有减低,但仅在PN组和PN-A组较术前有明显下降（P＜0.05）.结论 PN液中添加谷氨酰胺对创伤后减轻肠黏膜萎缩、维护肠屏障功能、减少肠道细菌移位以及维护机体细胞免疫功能有积极作用,而精氨酸并未显示出这些作用.     

高脂饲料对OLETF大鼠糖代谢及血清磷脂脂肪酸组成的影响

目的:观察高脂饲料对自发性2型糖尿病模型OLETF大鼠糖代谢及血清磷脂脂肪酸组成的影响。方法:将20只14w雄性OLETF大鼠随机分为两组,分别以高脂及标准饲料喂饲10w,两种饲料中饱和脂肪酸、单不饱和脂肪酸、多不饱和脂肪酸占总脂肪酸的百分含量相似。大鼠第24w龄时进行口服糖耐量试验,同时测定大鼠的胰岛素水平和血清磷脂脂肪酸组成。结果:实验期间两组大鼠总进食量无统计学差异,但高脂饲料组大鼠体重明显高于标准饲料组(P<0.01);口服糖耐量试验和胰岛素水平测定结果表明,两组大鼠的糖代谢状态无统计学差异;血清磷脂脂肪酸组成中,除总n-6PUFA和18:3(n-3)的百分含量无统计学差异外,其他各脂肪酸组分在两组间的差异均具有统计学意义(P<0.01)。结论:在饲料脂肪酸组成保持可比的情况下,饲料脂肪量的增加可使OLETF大鼠的体重明显增加,而对糖代谢的影响不明显,同时对OLETF大鼠血清磷脂脂肪酸组成产生明显影响。     

门静脉途径胃肠外营养的实验研究

利用脾切除术后狗的实验模型进行门静脉途径胃肠外营养(PN)可行性及营养支持效果的实验研究。23只狗随机分为两组。12只狗进行门静脉途径PN(PN—pv组),11只狗进行中心静脉途径PN(PN—cv)。手术后第1天起两组给予7天相同的营养支持(总热量60kc al·kg/d,氮0.384g·kg/d,葡萄糖6.3S·kg/d,脂肪2.8g·kg/d,非蛋白热量/氮=131.25)。7天后,PN-pv组TIBC明显高于PN-cv组且显著高于术前水平。PN-pv组术后第2、4、8天血糖显著低于PN-cv组。术后第4、8天,PN-pv组血浆缬氨酸,亮氨酸及异亮氨酸水平显著高于PN-cv,且两组均显著高于术前水平:PN-pv组,术后第3、7天尿3-甲基组氨酸排出量显著低于PN-cv组。肝脏组织学检查结果:PN-cv组发生肝细胞内淤胆6例,PN-pv组无一例发生。研究表明短期门静脉途径胃肠外营养是可行的。且效果优于中心静脉途径并可避免肝胆系统淤胆。     

Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia

The purpose of the present study was to test whether hyperlipidaemia and insulin resistance in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be improved by dietary supplementation with purified eicosapentaenoic acid (EPA) or oleic acid (OA). Male OLETF rats were fed powdered chow (510 g fat/kg) alone (n 8) or chow supplemented with 10 g EPA- (n 8) or OA- (n 8) rich oil/kg per d from 5 weeks until 30 weeks of age. An oral glucose tolerance test and hyperinsulinaemic euglycaemic clamp was performed at 25 and 30 weeks of age. EPA supplementation resulted in significantly (P<0.05) reduced plasma lipids, hepatic triacylglycerols, and abdominal fat deposits, and more efficient in vivo glucose disposal compared with OA supplementation and no supplementation. OA supplementation was associated with significantly increased insulin response to oral glucose compared with EPA supplementation and no supplementation. Inverse correlation was noted between glucose uptake and plasma triacylglycerol levels (r -086, P<0.001) and abdominal fat volume (r -0.80, P<0.001). The result of oral glucose tolerance test study showed that the rats fed EPA tended to improve glucose intolerance, although this was not statistically significant. Levels of plasma insulin at 60 min after glucose was significantly increased in rats fed OA compared with the other two groups. The results indicate that long-term feeding of EPA might be effective in preventing insulin resistance in diabetes-prone rats, at least in part, due to improving hypertriacylglycerolaemia.     

Effect of fat proportion to glucose in peripheral parenteral nutrition on nutritional status in normal rats

The purpose of this study was to determine the optimal fat proportion to glucose in peripheral parenteral nutrition (PPN). PPN solutions consisting of dextrose + amino acids + fat (0%, 10%, 20%, 30%, 40% or 50% of total energy as fat) were administered parenterally at a rate of 120 kcal/kg/day for 5 days to normal rats, after which the effects on the nutritional status were assessed. Body weight change and cumulative nitrogen balance during the 5 day PPN period tended to increase with increasing fat dose until the 40% fat group. Serum triglyceride (TG), phospholipid (PL), free fatty acid (FFA) and total cholesterol (T-CHO) levels increased with increasing fat dose. Specifically, PL, T-CHO and FFA levels in the 50% fat group were especially higher than that in the normal group. Although the rats were administered with the same composition and dose of amino acid, serum Thr, Trp, Ala and Pro levels tended to decrease with increasing fat dose, with serum Ala and Pro levels in the 50% fat group being lower than that in the normal group. Hepatic glycogen content also tended to decrease with increasing fat dose. These results suggest that gluconeogenesis in the liver is increased in the 50% fat group due to low dextrose dose. In the 40% fat group, although serum PL and T-CHO levels were significantly higher, hepatic glycogen content and serum Ala levels were not significantly different compared with 0% fat group. It was therefore concluded that the optimal fat proportion in the rats receiving an energy intake below the basal energy requirements is 40% of total energy as fat.     

五味子乙素对染矽大鼠肺组织MAPKs和NF-κB信号转导通路的影响

目的 探讨五味子乙素(Sch-B)对SiO2致大鼠肺损伤过程中肺组织丝裂素活化蛋白激酶(MAPKs)和核因子-κΒ(nuclear factor-κΒ,NF-κΒ)信号转导通路的影响.方法 92只大鼠随机分为对照组(20只)、染尘组(30只)、Sch-B干预1组(24只)和Sch-B干预2组(18只).非暴露气管法建立大鼠矽肺模型,Sch-B干预1组造模后第1天起连续灌胃(80mg/kg Sch-B)21 d,Sch-B干预2组造模后第8天起连续灌胃(80mg/kg Sch-B)21 d.Sch-B干预1组在第3、7、14和21天,Sch-B干预2组在第14、21和28天随机取6只,在第3、7、14、21和28天随机取对照组4只,染尘组6只,处死取其肺组织.右肺用于蛋白质提取,通过免疫印迹(Western bloting)法测定肺组织MAPKs家族中细胞外信号调节蛋白激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38的磷酸化水平;用免疫组化法测定NF-κΒ核转移率.结果 Sch-B干预1组第3、7、14和21天,Sch-B干预2组第21和28天肺组织ERK1/2磷酸化水平(0.974±0.169、0.987±0.149、0.920±0.092、0.884±0.078、1.167±0.083、1.002±0.060)均明显低于染尘组,差异均有统计学意义(P＜0.05或P＜0.01);Sch-B干预1组在第7天肺组织JNK1磷酸化水平达到最高峰后持续下降,与染尘组比较,差异有统计学意义(P＜0.01),而Sch-B干预2组第14、21和28天肺组织JNK1磷酸化水平(0.882±0.064、0.802±0.061、0.792±0.015)均低于染尘组,差异有统计学意义(P＜0.01);Sch-B干预1组第3天p38磷酸化水平为0.309±0.045,高于染尘组,Sch-B干预1组和2组第14天p38磷化水平为0.667±0.072和0.650±0.066,均明显低于染尘组,差异有统计学意义(P＜0.01).Sch-B干预1组大鼠肺组织第3、7、14和21天NF-κΒ核转移率为(13.54±5.36)%,(21.01±6.43)%,(30.55±6.44)%,(37.39±9.32)%,Sch-B干预2组第21天核转移率为(44.33±22.88)%,明显均低于染尘组,差异有统计学意义(P＜0.01),而在第28天Sch-B干预2组核转移率为(58.52±14.57)%,明显高于染尘组,差异有统计学意义(P＜0.01).结论 ch-B对SiO2诱导的肺组织损伤过程中MAPKs家族3个成员活化都有一定的抑制作用.在染矽初期给予Sch-B干预可抑制NF-κΒ活化.Sch-B对SiO2诱导的大鼠肺损伤保护作用可能通过MAPKs和NF-κΒ信号转导通路.     

Effects of dietary catechins on glucose tolerance, blood pressure and oxidative status in Goto-Kakizaki rats

Effects of green tea catechins comprising EGCg, EGC, ECg, EC, GCg, GC, Cg, and C were determined on blood glucose tolerance and oxidative stress status in type 2 diabetic Goto-Kakizaki (GK) rats. GK rats fed the catechin-containing diet tended to maintain blood glucose and systolic blood pressure at lower levels in the latter stages of the feeding period of 76 d, compared to those not receiving dietary catechins (control group). The blood glucose tolerance test performed on days 48-49 showed that GK rats fed the catechins had lower blood glucose levels than GK rats not fed catechins during the 120 min after glucose loading. In catechin-fed rats, amounts of 8-OH dG and albumin excreted into the urine determined on days 71-72, and kidney ACE activity determined on day 76, were lower than those in control rats. From these results it is concluded that dietary catechins may be effective in delaying the progression of diabetes and the associated oxidative stress.     

叶酸和维生素B12对宫内生长受限大鼠骨骼肌磷脂酰肌醇3激酶表达的影响

目的 探讨母鼠哺乳期补充叶酸和维生素B12对宫内生长受限(IUGR)仔鼠骨骼肌磷脂酰肌醇3激酶的蛋白激酶B(PI3K/AKT)胰岛素信号通路中关键分子磷脂酰肌醇3激酶( PI3K)表达的影响,并分析PI3K分子表达的改变与胰岛素抵抗的关系。方法 1)采用孕中晚期低蛋白及限制饮食的方法建立IUGR大鼠模型,将新生IUGR仔鼠随机分为IUGR干预组和IUGR未干预组,其中IUGR干预组的哺乳期母鼠饲以高叶酸和维生素B12的饲料(叶酸和维生素B12含量比普通饲料提高4倍),IUGR未干预组和对照组的哺乳期母鼠饲以正常标准饲料。三组仔鼠均于生后21 d断奶,饲以正常标准饲料至生后120 d。2)测定对照组、IUGR未干预组及IUGR干预组(每组各8只,雌雄各半)在生后21、60 d及120 d空腹血浆血糖(FPG)、空腹血清胰岛素(FINS),计算胰岛素抵抗指数(IRI)。3)在生后21、60 d和120 d分别留取3组仔鼠的骨骼肌组织,采用Real-Time PCR和Western Blotting法检测三组仔鼠骨骼肌组织中PI3K mRNA和蛋白表达情况。结果 1)低蛋白组仔鼠平均出生体重[(4.44±0.58)g]低于对照组[(7.03±0.56) g],差异有统计学意义(t=15.75,P<0.05),低蛋白组仔鼠中IUGR发生率为93.3%。2)生后21 d,三组仔鼠FPG、FINS和IRI差异均无统计学意义(P>0.05);生后60 d和120 d,IUGR干预组仔鼠的FPG、FINS和IRI均显著低于IUGR未干预组,但均高于对照组,差异均有统计学意义(P值均＜0.05)。3)生后21 d、60 d和120 d,三组仔鼠PI3K mRNA和蛋白表达水平均在对照组最高,IUGR干预组次之,IUGR未干预组最低,差异均有统计学意义(P值均＜0.05)。4)生后60 d和120 d,IUGR未干预和干预组仔鼠IRI与PI3K蛋白表达均呈负相关(P值均<0.05)。结论 母鼠哺乳期补充叶酸和维生素B12,影响了IUGR仔鼠骨骼肌PI3K/AKT胰岛素信号通路中关键分子PI3K的蛋白表达,且这些变化与胰岛素抵抗密切相关。