Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters

The aim of this study was to elucidate the mechanisms underlying the hypoglycaemic effect of N. sativa oil (Nigella sativa oil) in streptozotocin (STZ)-induced diabetic hamsters, in terms of hepatic glucose production, and to investigate the possible immunopotentiating effect of N. sativa oil on peritoneal macrophages. Diabetes was induced by intraperitoneal injection of 65 mg/kg body weight of STZ. Treatment with N. sativa oil commenced 6 weeks after induction of diabetes at a dose of 400 mg/kg body weight by gastric gavage. Isolated hepatocytes were collected using collagenase to determine liver glucose production. Phagocytic activity was evaluated by injection of fluorescent latex (2 microm diameter) intraperitoneally, followed 24 h later by collection of peritoneal macrophages. N. sativa oil reduced blood glucose from 391+/-3.0 mg/dl before treatment to 325+/-4.7, 246+/-5.9, 208+/-2.5 and 179+/-3.1 mg/dl after the first, second, third and fourth weeks of treatment, respectively. Hepatic glucose production from gluconeogenic precursors (alanine, glycerol and lactate) was significantly lower in treated hamsters. Treatment with N. sativa oil significantly increased the phagocytic activity and phagocytic index of peritoneal macrophages and lymphocyte count in peripheral blood compared with untreated diabetic hamsters. Our data indicate that the hypoglycaemic effect of N. sativa oil is due to, at least in part, a decrease in hepatic gluconeogenesis, and that the immunopotentiating effect of N. sativa oil is mediated through stimulation of macrophage phagocytic activity either directly or via activation of lymphocytes.     

Effect of dexamethasone on babesiasis in hamsters

Three subcutaneous injections of 0.20 mg of dexamethasone/kg of body weight caused a substantial increase in Babesia microti-parasitized RBC of hamsters, indicating that this was a useful method for revealing the presence of latent infections. A relative neutrophilia, lymphocytopenia, and eosinopenia were also seen in the long-term B microti-infected carrier hamsters after 0.20 mg or 0.02 mg of dexamethasone/kg. Noninfected hamsters treated with dexamethasone had a neutrophilic leukocytosis and a transient lymphocytopenia. Spleen to body weight ratios of noninfected hamsters decreased significantly (P less than 0.02) after 4 injections with either dosage level. These ratios did not significantly (P greater than 0.05) decrease in dexamethasone-treated infected hamsters.     

Diphenylamine-induced renal papillary necrosis and necrosis of the pars recta in laboratory rodents

The nephrotoxicity of diphenylamine, the parent compound of the mefenamate family of nonsteroidal anti-inflammatory drugs, was evaluated in male Syrian hamsters, male Sprague-Dawley rats, and male Mongolian gerbils. Total renal papillary necrosis was observed in four of ten, seven of ten, and six of ten male Syrian hamsters orally treated with diphenylamine at respective doses of 400 mg/kg body weight/day, 600 mg/kg body weight/day, and 800 mg/kg body weight/day. Total renal papillary necrosis was also observed in five of ten and four of ten male Syrian hamsters intraperitoneally treated with diphenylamine at respective doses of 600 mg/kg body weight/day and 800 mg/kg body weight/day. Focal intermediate renal papillary necrosis was induced in two hamsters orally given diphenylamine at 600 mg/kg body weight/day and in two of ten hamsters intraperitoneally given diphenylamine at 800 mg/kg body weight/day. Apex-limited necrosis of the medullary interstitial cells and vasa recta and degeneration of the renal interstitial matrix occurred in two Sprague-Dawley rats orally administered diphenylamine at 800 mg/kg body weight/day. Degeneration and necrosis of the pars recta was induced in seven of ten hamsters intraperitoneally given diphenylamine at 400 mg/kg body weight/day. Gross and microscopic renal lesions were not observed in any Mongolian gerbils. It was concluded that the Syrian hamster is more susceptible to the papillotoxic effects of diphenylamine than the Sprague-Dawley rat and the Mongolian gerbil. Renal papillary necrosis in the Syrian hamster treated orally with diphenylamine is reproducible, is of short onset, and is induced in a high proportion of the hamsters (70-90%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the metabolic and antioxidant effects of diltiazem and vitamin E on streptozotocin-diabetic rats

In this study, solitary and combined effects of vitamin E and the calcium-channel blocker diltiazem were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male Wistar albino rats, weighing approximately 200 g were used. Diabetes mellitus was induced by a single intravenous injection of STZ at a dose of 65 mg/kg body weight. Five experimental groups were established as STZ-diabetic, STZ-diabetic + vitamin E, STZ-diabetic + diltiazem and STZ-diabetic + vitamin E + diltiazem. Vitamin E was injected intraperitoneally three times a week at a dose of 500 mg/kg body weight. Diltiazem was given orally every day at a dose of 25 mg/kg body weight. At the end of the study (10 weeks) blood glucose levels of diabetic rats, which had received vitamin E and diltiazem, had significantly decreased when compared with untreated diabetic rats (P < 0.02). Similarly, HbA1c levels had significantly decreased in diabetic rats which had received vitamin E (P < 0.05), diltiazem (P < 0.01) and vitamin E + diltiazem (P < 0.02) when compared with untreated diabetic rats. Liver glutathione levels of diabetic rats, which had received vitamin E (P < 0.01) and vitamin E + diltiazem (P < 0.05) had significantly increased when compared with untreated diabetic rats. Liver lipid peroxide levels had significantly decreased in diabetic rats, which had received vitamin E (P < 0.001) and diltiazem (P < 0.01). With respect to their metabolic and antioxidant effects, vitamin E proved superior to diltiazem.     

Streptozocin-induced pancreatic islet destruction in beef cows.

Streptozocin (STZ) induces diabetes mellitus in sheep and pigs. To test the effect of STZ in cattle, cows were given 75-150 mg STZ per kilogram of body weight. Cows receiving 150 mg/kg required euthanasia within 24 hours after infusion because of the severe systemic effects of STZ. Seven cows receiving doses of < or = 100 mg/kg had mild to marked decrease in islet immunoreactivity for insulin and in pancreatic islet density and mild to severe tubulointerstitial nephritis. Two cows receiving 75 and 85 mg/kg STZ regained their ability to produce insulin and return blood glucose to basal levels. One cow given 100 mg/kg STZ developed insulin insufficiency consistent with type I diabetes mellitus. These findings demonstrate the susceptibility of the bovine pancreas to STZ: however, severe systemic complications were encountered. Alternative dosages and methodologies should be considered in future attempts to induce diabetes in cattle using STZ.     

High sensitivit to streptozotocin in herbivorous voles,Microtus arvalis,compared to mice

Herbivorous voles, Microtus arvalis, have characteristics similar to herbivores in that their hepatic glycolytic enzyme activities are relatively low. The effects of a single low dose (100 mg/kg body weight) of streptozotocin (STZ) in voles were studied and the difference in sensitivity to or toxicity of STZ in voles and C57BL/6 mice was compared. In voles which received STZ, the cumulative incidence of glycosuria reached 53% by 4 weeks after administration. The diabetic voles showed marked increas in their blood glucose and plasma free fatty acid concentrations and a significant decrease in plasma immunoreactive insulin concentrations. Their hepatic hexokinase, glucokinase, glutathione peroxidase and glutamate dehydrogenase activities decreased significantly and lesions were widely observed in the liver, kidney and pancreas. The activities of glutathione peroxidase, a scavenger of H₂O₂, decreased significantly in their liver and pancreas. These changes were not observed in C57BL/6 mice which received STZ. The higher sensitivity to and toxicity of STZ in voles than in mice are considered to be caused by the characteristically low activities of glycolytic enzymes and glutathione peroxidase in the tissues of voles. Voles may be a good model for studying the mechanisms of cytotoxicity by STZ in herbivorous animals.Abbreviations GK glucokinase - GIDH glutamate dehydrogenase - GSH-px glutathione peroxidase - HE haematoxylin-eosin - HK nexokinase - IRI immunoreactive insulin - STZ streptozotocin     

牛初乳粉预防大鼠高血糖的实验研究

目的:探讨牛初乳粉对大鼠糖尿病的预防作用。 方法:给大鼠灌胃3个不同剂量的牛初乳粉(BCP)溶液15d后腹腔注射链脲霉素(STZ)55mg/kg。注射后第7、14天测定各项指标(平均饮水量在注射后第6、13天测量)。血糖用Roche公司血糖仪测定,血脂用Beckman公司全自动生化分析仪测定,肝肾组织SOD、GSH-Px、NOS及MDA均用南京建成生物工程研究所相应试剂盒测定。结果:注射STZ后第7、14天中剂量BCP组的血糖均显著低于STZ组(P<0.05,P<0.01)。第13天中剂量组的平均饮水量的数值小于STZ组。第14天BCP各组的体重、胸腺指数与STZ组相比差异均无显著性,5个组之间的血脂、肝MDA、肝肾SOD、GSH-Px、NOS差异均无显著性。 结论:预防性给予BCP可预防STZ所致的高血糖,并使STZ大鼠平均饮水量减少(中剂量);但不能使STZ大鼠降低了的体重及胸腺指数恢复。     

Time-dependent changes of calbindin D-28K and parvalbumin immunoreactivity in the hippocampus of rats with streptozotocin-induced type 1 diabetes

The hippocampus is affected by various stimuli that include hyperglycemia, depression, and ischemia. Calcium-binding proteins (CaBPs) have protective roles in the response to such stimuli. However, little is known about the expression of CaBPs under diabetic conditions. This study was conducted to examine alterations in the physiological parameters with type 1 diabetes induced with streptozotocin (STZ) as well as time-dependent changes in the expression of two CaBPs changes of were being evaluated. Rats treated with STZ (70 mg/kg) had high blood glucose levels (>21.4 mmol/L) along with increased food intake and water consumption volumes compared to the sham controls. In contrast, body weight of the animals treated with STZ was significantly reduced compared to the sham group. CB-specific immunoreactivity was generally increased in the hippocampal CA1 region and granule cell layer of the dentate gyrus (DG) 2 weeks after STZ treatment, but decreased thereafter in these regions. In contrast, the number of PV-immunoreactive neurons and fibers was unchanged in the hippocampus and DG 2 weeks after STZ treatment. However, this number subsequently decreased over time. These results suggest that CB and PV expression is lowest 3 weeks after STZ administration, and these deficits lead to disturbances in calcium homeostasis.     

Effect of spontaneous hyperadrenocorticism on endogenous production and utilization of glucose in the dog

Alterations in carbohydrate metabolism were evaluated in 15 dogs with untreated hyperadrenocorticism by measuring basal plasma concentrations of glucose and insulin and determining the rates of hepatic glucose production and overall glucose uptake by tissues using 6-³H-glucose as the tracer. Of the 15 dogs, 8 (53%) had fasting hyperglycemia and 12 (80%) had insulin resistance, evidenced by mild to severe endogenous hyperinsulinemia together with euglycemia or hyperglycemia. Mean rates of both hepatic glucose production (323.1 mg/kg/hr) and tissue utilization of glucose (319.2 mg/kg/hr) were significantly (P<0.001) increased in the dogs with hyperadrenocorticism, compared to the glucose turnover rate in normal dogs (169.9 mg/kg/hr). Despite the increased glucose utilization rates, the mean rate of glucose clearance remained normal in the dogs with hyperadrenocorticism.In 6 dogs re-evaluated after treatment of hyperadrenocorticism, insulin resistance and glucose intolerance improved or resolved, evidenced by decreases in the mean plasma concentrations of both insulin and glucose into the normal range. After correction of glucocorticoid excess and associated insulin resistance, elevated rates of glucose production and utilization also decreased significantly (P<0.005) and normalized in all dogs.In results of this study indicate that increased glucose production and utilization are characteristic of spontaneous canine hyperadrenocorticism. Despite the increased rates of glucose tissue uptake, the normal glucose clearance rates found in these dogs suggest relative impairment of overall glucose utilization. Nevertheless, it appears that hepatic glucose overproduction plays the major role in the development of the hyperglycemia commonly associated with canine hyperadrenocorticism.     

Thymoquinone enhances the activities of enzymes related to energy metabolism in peripheral leukocytes of diabetic rats

The aim of this study was to examine the effect of glycemic control using thymoquinone (TQ) on energy metabolism related enzymes in leukocytes of streptozotocin (STZ)-induced diabetic rats. The treatment of both TQ and insulin commenced 4 weeks after induction of diabetes. Plasma glucose, cholesterol and triglycerides levels were significantly reduced after TQ treatment, whereas immunoreactive insulin (IRI) showed significant increase. The activities of malate dehydrogenase (MDH) in cytosolic and mitochondrial fractions of peripheral blood leukocytes were significantly higher in rats treated with TQ and insulin as compared to that in diabetic controls. On the other hand the activities of lactic dehydrogenase (LDH) showed no significant changes between groups. ML ratio (cytosolic MDH/LDH specific activity ratio) was restored to those in the control rats. The results of this study demonstrate that TQ significantly increased insulin level and the activities of cytosolic and mitochondrial MDH in leukocytes of STZ-diabetic rats.     

Effect of Escherichia coli endotoxin on tissue lipoprotein lipase activities in chickens

1. Four-week-old broiler chickens were injected intravenously with from 0.01 to 1 mg of E. coli endotoxin/kg body weight or with saline. 2. At all doses used endotoxin markedly depressed food intake and lipoprotein lipase activities in muscle and adipose tissue within 8 h. Heart lipoprotein lipase activity was significantly depressed only at doses of 0.1 mg endotoxin/kg body weight or greater. 3. Treatment of birds with 0.3 mg endotoxin/kg body weight reduced post-heparin lipoprotein lipase activity to 0.13 of that in control birds in 8 h. 4. Endotoxin generally depressed plasma very-low-density lipoprotein concentration. Plasma non-esterified fatty acid concentration was significantly elevated only in birds given 1 mg endotoxin/kg body weight. 5. Fatty acid synthetase activity in the liver of endotoxin-treated birds was significantly lower than in control birds 16 h after administration of endoxin, but not after 8 h. 6. These results show that tissue lipoprotein lipase activity in birds is very responsive to E. coli endotoxin, as in mammals. Hypertriglyceridaemia occurs only occasionally in endotoxin-treated chickens, most probably because of the particularly close relationship between food intake and hepatic lipoprotein synthesis in birds.     

不同剂量链脲佐菌素及不同性别大鼠糖性白内障模型的比较研究

本试验旨在研究不同剂量链脲佐菌素(streptozocin,STZ)及不同性别在建立大鼠糖性白内障模型方面的差异。将65、70和75 mg/kg 3个浓度STZ通过一次性腹腔注射建立雌、雄性大鼠糖性白内障模型,36 h后尾静脉采血测血糖,3周后进行裂隙灯检查,每天测量动物饮食量及排粪尿量变化,每周测定体重。试验结果显示,70 mg/kg STZ比65 mg/kg STZ糖性白内障发生时间缩短约1周,且比75 mg/kg STZ死亡率低。同浓度STZ腹腔注射后雌性大鼠糖尿病发生时间为72 h,雄性大鼠为36 h,白内障发生时间雌性比雄性大鼠慢约1周。试验结果表明,腹腔注射70 mg/kg STZ在糖性白内障模型建立所需时间及模型稳定性等方面具有优势,雄性大鼠较雌性更易于建立糖性白内障模型。     

Thioacetamide-induced Hepatocellular Necrosis Is Attenuated in Diet-induced Obese Mice

To assess modification of thioacetamide-induced hepatotoxicity in mice fed a high-fat diet, male C57BL/6J mice were fed a normal rodent diet or a high-fat diet for 8 weeks and then treated once intraperitoneally with thioacetamide at 50 mg/kg body weight. At 24 and 48 hours after administration, massive centrilobular hepatocellular necrosis was observed in mice fed the normal rodent diet, while the necrosis was less severe in mice fed the high-fat diet. In contrast, severe swelling of hepatocytes was observed in mice fed the high-fat diet. In addition, mice fed the high-fat diet displayed more than a 4-fold higher number of BrdU-positive hepatocytes compared with mice fed the normal rodent diet at 48 hours after thioacetamide treatment. To clarify the mechanisms by which the hepatic necrosis was attenuated, we investigated exposure to thioacetamide and one of its metabolites, the expression of CYP2E1, which converts thioacetamide to reactive metabolites, and the content of glutathione S-transferases in the liver. However, the reduced hepatocellular necrosis noted in mice fed the high-fat diet could not be explained by the differences in exposure to thioacetamide or thioacetamide sulfoxide or by differences in the expression of drug-metabolizing enzymes. On the other hand, at 8 hours after thioacetamide administration, hepatic total glutathione in mice fed the high-fat diet was significantly lower than that in mice fed the normal diet. Hence, decreased hepatic glutathione amount is a candidate for the mechanism of the attenuated necrosis. In conclusion, this study revealed that thioacetamide-induced hepatic necrosis was attenuated in mice fed the high-fat diet.     

枸杞多糖对己烯雌酚生殖损伤仓鼠抗氧化能力及生殖激素水平的影响

为探讨枸杞多糖（LBP）对己烯雌酚（DES）致成年雄性仓鼠生殖损伤的保护作用,66只成年雄性仓鼠随机分为空白对照组（A）、DES组（B）、LBP组（C、D、E）及VC＋VE组（F）。除对照组注射橄榄油外,其余5组皮下注射DES,连续用药7d,同时C、D、E组分别灌服1,10,50mg/kg的LBP,F组灌服100mg/kg的VC及200IU/kg的VE,A、B组灌服等剂量的生理盐水,于末次给药24h后取材。摘取睾丸、附睾和精囊腺测质量并观察睾丸组织结构,检测血清中SOD、GSH-Px、MDA及T、LH、FSH、E2的水平。结果显示,DES能显著降低仓鼠体质量及生殖器官质量,而10,50mg/kg LBP及维生素对其有显著缓解作用（P〈0.05）;DES处理组仓鼠睾丸组织结构严重损伤,应用LBP后其损伤程度显著减轻,其中以10,50mg/kg LBP的作用最为明显,VC＋VE的缓解作用与50mg/kg LBP组接近;随着LBP剂量的增加,血清中SOD、GSH-Px的水平增加（P〈0.01）,而MDA的水平下降（P〈0.01）,维生素组与LBP组的变化趋势一致;LBP对血清激素水平也有不同程度的提高,其中以50mg/kg作用最为显著（P〈0.01）。这表明50mg/kg LBP能显著缓解DES致成年雄性仓鼠睾丸生精损伤。     

LIVER METABOLISM DURING MALIGNANT HYPERTHERMIA IN THE PIETRAIN PIG

Liver function was systematically investigated in 7 malignant hyperthermia (MH) susceptible Pietrain pigs (mean weight 67 kg ± 7 kg SEM) to determine the contribution of hepatic metabolism to circulating substrates (Hall, Lucke, Lovell and Lister 1978). It was considered that the progressive lactic acidosis observed in MH may be a result, not only of impaired hepatic uptake of lactate but also production of lactate by the liver as is said to occur in Type II lactic acidosis (Cohen and Simpson 1975). These authors suggested that as the enzyme pyruvate decarboxylase is pH sensitive, and because it is rate limiting in the gluconeugenic pathway of lactate to glucose, under conditions of severe acidosis (pH 7.1) hepatic lactate uptake will be inhibited and there will be production of lactate by the liver. Pigs were prepared with hepatic vein, right ventricle and common carotid artery cannulae. Control measurements were made before inducing MH by ventilating with 1% halothane for 10 minutes together with intravenous injection of 1 mg suxamethonium chloride per kg body weight. Paired arterial and hepatic venous samples were collected at 10 minute intervals for the following estimations: pH, oxygen content, glucose, potassium, lactate, pyruvate, alanine, free fatty acids and glycerol. Hepatic blood flow was estimated by continuous infusion of Indocyanine green (Lucke and Hall 1978). All pigs developed MH with a rise in mean muscle temperature from 37.8°C to 41.5°C after 40 minutes. Mean hepatic blood flow decreased to 25% of control value but, because there was a concomitant increase in oxygen extraction by the liver, hepatic oxygen consumption did not change significantly. At 20 minutes after MH there was a 7-fold increase in glucose efflux from the liver with an arterial glucose concentration of 12.6 mmol/1. There was a massive efflux of 1.1 mmol K+/min early in the response showing that the characteristic hyperkalaemia is not only due to potassium loss from muscle but mainly hepatic in origin. The mean lactate uptake by the liver increased from the control 0.21 mmol/min to 1.19 mmol/min after 10 minutes MH. Even in the presence of gross acidosis (mean pH 6.75) and hepatic blood flow 25% of control, hepatic lactate uptake was still 3 times that recorded in the resting state. It is important to note, however, that although hepatic lactate uptake was increased under these conditions, it was still insufficient in the presence of gross muscle stimulation with a mean arterial lactate concentration of 19.3 mmol/l. It is concluded that the lactic acidosis in porcine MH is due to peripheral overproduction with some impairment of hepatic uptake. The gluconeugenic capacity of the liver was never completely inhibited despite the severity of the metabolic acidosis and hyperthermia and at no stage was there production of lactate by the liver.     

Effect of Weight Gain and Subsequent Weight Loss on Glucose Tolerance and Insulin Response in Healthy Cats

The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre-study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat. Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P > .05) increased after weight gain, as compared with baseline. At the end of weight loss, cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P > .05) increase in mean serum glucose concentration and t_1/2, and a significant (P > .05) decrease in mean serum insulin concentration and the glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulino-genic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P > .05), compared with measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P > .05) in measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the number and size of lipid vacuoles in hepatocytes had decreased, and results of IVGTT were similar to those obtained at baseline. These findings confirmed the reversibility of obesity-induced insulin resistance in cats, and documented initial deterioration in glucose tolerance and insulin response to glucose infusion when weight loss was caused by severe restriction of caloric intake.     

叶酸对超早期断奶宫内发育迟缓仔猪肝脏结构和细胞凋亡相关基因表达的影响

本试验旨在研究饲粮添加不同水平叶酸对超早期断奶宫内发育迟缓(IUGR)仔猪肝脏结构和细胞凋亡相关基因表达的影响。选取24头14日龄断奶、平均体重(2.79±0.34)kg的"杜×长×大"三元杂交仔公猪,随机分为3个处理,分别饲喂在基础饲粮中添加0、5和10 mg/kg叶酸的试验饲粮,每个处理8个重复,每个重复1头猪。试验期21 d。结果表明:1)饲粮添加叶酸对35日龄仔猪血清葡萄糖浓度无显著影响(P>0.05),添加5和10 mg/kg叶酸分别显著(P<0.05)和极显著(P<0.01)降低了血清甘油三酯浓度。2)饲粮添加5 mg/kg叶酸能显著降低肝细胞直径(P<0.05)。3)饲粮添加5 mg/kg叶酸显著提高了肝脏B细胞淋巴瘤蛋白2(Bcl-2)的基因表达量(P<0.05),极显著降低了Bcl-2相关X蛋白(Bax)和促凋亡相关基因肿瘤蛋白53(p53)的基因表达量(P<0.01);饲粮添加10 mg/kg叶酸,Bax和p53的基因表达量分别极显著(P<0.01)和显著(P<0.05)地降低了。4)饲粮添加叶酸对肝脏毛细血管扩张性共济失调症突变基因(ATM)、脱嘌呤嘧啶核酸内切酶1(APE-1)基因和一碳单位代谢关键酶编码基因的表达无显著影响(P>0.05)。结果提示,饲粮补充一定水平的叶酸有助于改善早期断奶IUGR仔猪35日龄时肝脏结构和细胞凋亡相关基因Bcl-2、Bax和p53的表达;本试验条件下,饲粮添加5 mg/kg叶酸效果较好。     

SD大鼠2型糖尿病模型的建立及相关指标的测定

通过链脲佐菌素(STZ)结合高糖高脂饮食诱导建立2型糖尿病大鼠模型。30只健康雄性SD大鼠随机分为模型组(20只)、空白组(10只)。模型组喂饲高糖高脂饲料4周后,用STZ 30mg/kg一次性左下腹腔注射。检测试验第1周、第4周,注射STZ后第1周、第4周、第8周、第12周空腹体重、血清葡萄糖(BG)、甘油三酯(TG)、胆固醇(TC)、胰岛素(INS)、葡萄糖依赖性促胰岛素释放肽(GIP)、胰岛素样生长因子1(IGF-1)、胰高血糖素样多肽-1(GLP-1)等指标,进行统计分析。处死大鼠,取胰腺进行病理切片检查。动物成模率为75%。试验第4周,模型组TG、TC值明显升高,与空白组比较,P<0.01。注射STZ后第1、4、8、12周,模型组BG、TG、TC值均明显升高,与空白组比较,P<0.01;ISI均明显降低,与空白组比较,P<0.01。注射STZ后第1、4、8周,模型组的GLP-1、IGF-1值明显降低,与空白组比较,P<0.01。注射STZ后第12周,模型组的GLP-1、GIP、IGF-1值明显降低,与空白组比较,P<0.01。试验结果表明,STZ一次性左下腹腔注射结合高糖高脂饮食可成功诱导2型糖尿病大鼠模型。GIP、IGF-1、GLP-1等细胞因子参与了2型糖尿病的病理发生。     

SD大鼠2型糖尿病动物模型的建立及胰腺组织SUR1 mRNA的表达

[目的]链脲佐菌素（streptozotocin,STZ）结合高糖高脂饮食诱导建立2型糖尿病大鼠模型,检测体重、血糖、胰岛素、胰岛素敏感指数（ISI）、胰腺组织SUR1 mRNA表达的变化。[方法]30只健康雄性SD大鼠随机分为模型组（20只）、空白组（10只）。模型组喂饲高糖高脂饲料4周后,用STZ 30mg/（kg·bw）一次性左下腹腔注射。检测注射STZ后第1周、第4周、第8周、第12周空腹体重、血糖、胰岛素、胰岛素敏感指数等指标,进行统计分析。剖杀大鼠,取胰腺,RT-PCR方法检测胰腺组织SUR1 mRNA的表达。[结果]动物成模率为75%。注射STZ后1、4、8、12周,模型组血糖值均明显升高,与空白组比较,P〈0.01;ISI均明显降低,与空白组比较,P〈0.01。模型组SUR1 mRNA表达显著低于对照组（P〈0.05）。[结论]STZ一次性左下腹腔注射结合高糖高脂饮食可成功诱导2型糖尿病大鼠模型。SUR1 mRNA的降低可能是糖尿病发病的分子机制之一。     

2种降脂药物对高脂饮食金黄地鼠肝脏组织病理学影响比较研究

旨在比较辛伐他汀与依折麦布对高脂饮食金黄地鼠降脂效果的差异。选取体况健康的雄性叙利亚金黄地鼠40只随机分为4组,分别为空白对照组、高脂模型组、辛伐他汀组和依折麦布组;空白对照组饲喂基础饲料,其他3组饲喂高脂饲料;采用灌胃方法分别给予高脂饲喂的金黄地鼠辛伐他汀与依折麦布,连续灌胃9周,空白对照组和高脂模型组同期灌胃蒸馏水;试验结束时,称量各组金黄地鼠体重,取肝脏样本进行称重,计算肝体比;制备肝脏组织学切片进行HE染色,利用显微镜观察病理变化。结果表明:与空白对照组相比,辛伐他汀组的肝脏重量极显著增加(P<0.01),依折麦布组的肝脏重量变化不显著(P>0.05);辛伐他汀组的肝体比极显著高于空白对照组(P<0.01),依折麦布组的肝体比显著低于空白对照组(P<0.05);辛伐他汀组肝脏颜色呈土黄色,表面有颗粒感,边缘锐利,眼观特征与高脂模型组相似;依折麦布组肝脏与空白对照组肝脏眼观特征一致,均呈暗褐色,质地柔软,边缘锐利;辛伐他汀组肝脏镜检观察可见肝周边缘部肝细胞质内出现大脂肪空泡,将细胞核挤向一边,可见空泡变性和炎性细胞浸润;依折麦布组肝脏组织学检查可见肝细胞均质红染,胞质丰富,未见大脂肪空泡、空泡变性和炎性细胞浸润,肝索排列整齐。综上提示,依折麦布对高脂饲喂的金黄地鼠肝脏的降脂效果优于辛伐他汀。