Total parenteral nutrition decreases liver oxidative metabolism and antioxidant defenses in healthy rats: comparative effect of dietary olive and soybean oil

BACKGROUND: Total parenteral nutrition (TPN) is used for critically ill patients undergoing surgery, after trauma, or during disease conditions that favor oxidative stress. We studied the effect of TPN on liver oxidative metabolism and antioxidant defenses in rats, and we compared the effect of soybean oil- and olive oil-based diets. METHODS: Seven-week-old rats (n = 28) were divided into four groups. Two experimental groups received a TPN solution containing soybean oil (TPN-S) or a mixture of olive/soybean oil, 80/20 (TPN-O), IV for 6 days. Orally fed animals received a solid diet including soybean oil (Oral-S) or olive/soybean oil, 80/20 (Oral-O). The following parameters were measured: DL-alpha-tocopherol, vitamin A, malondialdehyde and thiobarbituric acid reactive substances (MDA-TBARS), and total radical-trapping antioxidant parameter (TRAP) in serum; DL-alpha-tocopherol, vitamin A, glutathione (GSH), and catalase (Cat) activity in liver homogenate; fatty acids from phospholipid, cytochrome P-450 content, NADPH-cytochrome c2 reductase activity in liver microsomes; superoxide dismutase (SOD), glutathione peroxidase (Gpx), glutathione reductase (GR), glutathione transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) in liver cytosol. RESULTS: The soybean or olive oil diets modified the liver microsomal fatty acid phospholipid composition, but the unsaturation index remained unchanged. TPN specifically increased the saturation of the membrane. The cytochrome P-450 level and the NADPH-cytochrome c2 reductase, SOD, Gpx, Cat, and GST activities were unchanged by soybean oil or olive oil diet but decreased receiving TPN. CONCLUSIONS: In rats, TPN decreased the liver oxidative metabolism and enzymatic antioxidant defenses. This may be related to saturation of the liver microsomal fatty acids.     

The Henry M. Vars Award. The effect of lipid emulsions on reticuloendothelial system function in the injured animal

Use of intravenous lipid emulsions in trauma and sepsis still remains controversial. In order to examine the impact lipid emulsions have on host defense against bacterial infection during total parenteral nutrition (TPN), 56 male Sprague-Dawley rats underwent jugular cannulation and were randomly divided into three groups, each receiving one of three TPN regimens. All regimens delivered approximately 250 kcal/kg X body weight/day, of which 12.5 g were as amino acids. Group 1 received 100% of the nonprotein calories as glucose (AA + G). Group 2 was given 50% of the nonprotein calories as a longchain triglyceride emulsion (100% LCT). Group 3 received 50% of nonprotein calories as a mixed lipid system, composed of medium- and long-chain triglycerides (75% MCT/25% LCT). After 24 hr on intravenous nutrition, all animals received bilateral septic femur fractures and were continued on TPN for 3 days. On the last day, the level of bacteremia and the in vivo response to an intravenous challenge of 59Fe-labeled Escherichia coli were examined. Three days following the septic injury, animals given MCT as part of their lipid calories were not bacteremic, whereas the other groups had greater than 10(2) cfu/ml of blood. Animals receiving TPN with MCT sequestered a greater percentage of exogenously administered bacteria in the liver and sequestered less in the lung compared to animals given 100% LCT (p less than 0.05). From these data, we conclude that parenteral nutrition formulas where LCT has been partially replaced with MCT may better support host bactericidal capacity than similar regimens comprised of LCT as the sole lipid source.     

Effects of three intravenous lipid emulsions on the survival and mononuclear phagocyte function of septic rats

The immunosuppressive effects of intravenous lipid emulsions are a matter of great concern and debate. In a rat model of gram-negative bacteremia, we assessed whether the use of three intravenous lipid emulsions with different triacylglycerol compositions could influence mortality, bacterial clearance, and prostaglandin E(2) (PGE(2)) levels and compared these groups with groups of orally fed rats and rats that received a small amount of calories in form of glucose without enteral feeding (starvation).RATS WERE ASSIGNED TO ONE OF FIVE GROUPS: group 1 (control, n = 15) received rodent chow ad libitum and saline infusion; group 2 (starvation group, n = 12) had no access to chow and received an infusion of 5% glucose; group 3 (n = 17) received total parenteral nutrition (TPN) with long-chain triacylglycerols; group 4 (n = 12) received TPN with medium- and long-chain triacylglycerols; and group 5 (n = 15) received TPN with its emulsion based on olive oil. Animals received isonitrogenous and isocaloric TPN. After 2 d of TPN, a dose of 10(8) colony-forming units of Escherichia coli was introduced via the venous catheter; 2 d later the animals were killed. Blood, spleen, liver, and lungs were cultured. Circulating levels of PGE(2) were measured.Bacterial growth in the liver and lungs were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Rates of bacteremia were significantly higher in groups 3 and 4 than in group 1, with no differences among the other groups. Plasma levels of PGE(2) did not differ, and mortality was unaffected.Bacterial clearance clearly was preserved in orally fed, control rats when compared with rats on TPN with long-chain triacylglycerols or medium- plus long-chain triacylglycerols. However, the use of a lipid emulsion enriched intravenously with oleic acid was a valid way of reducing this disturbance, although plasma levels of PGE(2) and survival were not modified.     

Short-chain fatty acids and total parenteral nutrition affect intestinal gene expression

BACKGROUND: The supplementation of total parenteral nutrition (TPN) formulas with short-chain fatty acids (SCFAs) increases glucose uptake and the expression of glucose transporters in parenterally fed animals. Several signals may be involved in intestinal adaptation; however, increased messenger RNA (mRNA) levels for proglucagon and several early-response genes, including c-myc and c-fos, are seen in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of SCFAs are well documented, the relative contribution of individual SCFAs is unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on cellular proliferation and gene expression. Accordingly, this study was undertaken to determine the relative role of butyrate in initiating an adaptive response in nonresected rats receiving TPN. METHODS: Animals received standard TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an elemental diet, similar in macronutrient content to the TPN, so that all animals received the same amount of energy daily. RESULTS: SCFAs increased ileal glucose transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs also increased proglucagon mRNA expression compared with the TPN group. No changes in Na+K(+)-adenosine triphosphatase or early-response gene expression were found in this study. CONCLUSIONS: In a rat model of TPN, the use of 9 mmol/L butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60-mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on intestinal gene expression is not butyrate specific.     

合成油的营养评价——(三)在实验性高脂血症大鼠的恢复期中合成油对其体重、肝重、血脂与肝脂水平的影响

在12％猪油饲料中加入胆固醇和胆酸饲养雌性断乳大鼠52日,以诱导动物产生高胆固醇血症。然后根据血清胆固醇水平和体重将大鼠分为4组,其中1组被处死作为负对照,另3组则分别饲以无胆固醇和胆酸的合成油,猪油或豆油饲料3周,观察不同油脂饲料对大鼠恢复的影响。在实验期内,测量体重、记录摄食量、测定粪的类固醇排出量、测定血清胆固醇总量和HDL含量、称量肝重和测定肝胆固醇含量。实验结果如下: (1)在恢复期的3周内,合成油组的动物体重增加和摄食量均显著低于其他两组。用共变数分析方法消除其摄食量的影响后,各组动物的体重增加尤显著性差别。 (2)52日诱导期末,大鼠血清总胆固醇量平均增为450mg/dl。恢复期的第一周即下降了60％,但到第3周时仍未能恢复到正常水平。3个组在任何一周的均值都未现出明显不同。 (3)HDL-C的测定结果指出在3周的恢复期后,猪油组的明显低于其他两组。 (4)动物的肝重和肝脂含量的恢复情况相似。肝胆固醇水平则以猪油组的较高,合成油和豆油组的均值间无显著性差别。 (5)粪的固醇平衡实验结果表明,在恢复期,猪油饲料组动物的粪中性类固醇排出量最低,固醇平衡量最高。 总结上述结果,可以看到在大鼠高胆固醇血症的恢复过程中,饲料油的种类对动物的体重、血清胆固醇、肝重和肝脂含量无     

Effect of structured lipids as energy substrate after hepatectomy in rats with streptozocin-induced diabetes.

The suitability of energy substrates for use by the remnant liver after 70% hepatectomy was studied in relation to the hepatic energy status in diabetic rats. Rats with streptozocin-induced diabetes underwent 70% hepatectomy and were divided into five groups receiving total parenteral nutrition (TPN) for 24 h. One group received standard TPN without fat, and four groups respectively received standard TPN with long-chain triglycerides (LCTs), medium-chain triglycerides (MCTs), mixed triglycerides (MIX), or structured lipids (SLs) as a 10% lipid emulsion. The latter groups received 60% of nonprotein calories per day with fat emulsion (LCT, MCT, MIX, or SL), and the remaining 40% with glucose. The group that received 100% of nonprotein calories per day with glucose was defined as the TPN group. All rats in the TPN group died from nonketotic hyperosmolarity within 24 h. The blood ketone body ratio (acetoacetate/beta-hydroxybutyrate), the energy charge level of the remnant liver, and the cumulative excretion of 14CO2 in expired breath during 6 h after [14C]glucose administration were all significantly higher in the SL group than in the other groups 24 h after hepatectomy. These findings suggest that SL may be a superior energy substrate to other triglyceride preparations during the immediate posthepatectomy phase in diabetic patients.     

Significance of administration of fat emulsion: hepatic changes in infant rats receiving total parenteral nutrition with and without fat

Total parenteral nutrition (TPN) is associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present animal study focused on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. Thirty infant (3-week-old) male SD rats weighing 60-70 g were randomly allocated to five groups (n = 6): the OD group received an oral diet, the FT group received an oral diet and was fasted overnight on the last day of experiment before sacrifice, the 0% fat group received TPN without fat, the 20% fat group received TPN with 20% of calories from fat emulsion, and the 40% fat group received TPN with 40% of calories from fat emulsion. All TPN regimens were isocaloric, isonitrogenic, and administered for 4 days. In the 0% fat group, plasma levels of liver enzymes were significantly higher than in the other groups. Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the 0% fat group. The results of this study in infant rats indicate the importance of including fat in the TPN regimen in order to prevent the abnormal hepatic changes associated with the excessive administration of fat-free TPN.     

Effects of intravenous nutrition on lipoprotein metabolism, body composition, weight gain and uremic state in experimental uremia in rats

The effect on serum lipids, lipoprotein fractions, body composition, weight gain and uremic state of including fat in intravenous nutrition was evaluated in rats with chronic uremia. Uremic rats were given high energy (1385 kJ.kg body weight-1.day-1), low nitrogen (0.6 g N.kg body weight-1.day-1) total parenteral nutrition (TPN) for 12 d with either glucose or glucose plus 30% lipids (Intralipid) as the energy source. Additional uremic and nonuremic groups were fed a standard diet orally. During TPN, serum triglyceride and cholesterol levels were slightly higher in rats fed lipid-based TPN compared to those administered glucose-based TPN or fed the oral diet; but there were no differences 8 h after feeding. The serum lipoprotein fractions showed accumulation of lipids in LDL resulting from the lipid-based TPN but no differences in VLDL. In orally fed uremic rats, more lipids were found in HDL than in the TPN-treated rats. The fractional clearance of the fat emulsion was normal and independent of the nutrition composition. Uremic rats administered lipid-based TPN for 21 d had the same weight gain as orally fed, nonuremic control rats (23 +/- 3 vs. 22 +/- 2%); glucose-based TPN did not support normal growth (10 +/- 1%). Uremic rats fed orally did not grow and retained significantly more body water than TPN-fed uremic rats. In uremic animals, lipid-based TPN also was associated with normal body composition despite significantly lower levels of carnitine in plasma, skeletal muscle and heart tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine supplementation does not prevent small bowel mucosal atrophy after total parenteral nutrition in the rat

Glutamine supplementation to non-lipid parenteral nutrition has been demonstrated to attenuate villus atrophy and increase mucosal DNA content in the rat. This study was performed in order to determine the effects of glutamine supplementation to a balanced TPN mixture (including lipids) on epithelial cell kinetics using autoradiography. Male Sprague-Dawley rats were used. Group 1 (control) received food and an intravenous saline infusion. Group 2 received an intravenous TPN mixture including lipids but without glutamine. The same TPN mixture, glutamine replacing an isonitrogenous amount of non-essential amino acids, was given to Group 3. Animals were fed for 7 days, whereafter blood and intestinal samples were taken 1 h after injection of tritiated thymidine. Microscopy of specimens from proximal jejunum revealed a significant reduction in the number of cells in crypts and villi in both TPN groups (2 and 3) compared to orally fed animals (p < 0.001). Epithelial cell numbers were not significantly different in Group 2 and 3. Similarly, the labelling index (number of labelled cells/number of crypt cells) was not affected by glutamine administration. In plasma, glucagon concentrations in Group 2 (TPN without glutamine) seemed to decrease compared to Group 1 and 3 (p = 0.06). In this study, glutamine supplementation did not affect apithelial atrophy or cell proliferation. It is concluded, that the effects of glutamine on mucosal atrophy and renewal in jejunum may depend on the composition of the TPN mixture supplied during parenteral feeding.     

Effects of glutamine-enriched total parenteral nutrition on acute pancreatitis

AIM: This study was performed to determine the effects of glutamine enriched total parenteral nutrition (TPN) on the patients with acute pancreatitis (AP). METHOD: Forty patients with AP, who had Ranson's score between 2 and 4 received either standard TPN (control group) or TPN with glutamine (treatment group). The patients in the treatment group received TPN containing 0.3 g/kg/days glutamine. At the end of the study, patients were evaluated for nutritional and inflammatory parameters, length of TPN and length of hospital stay. RESULTS: The length of TPN applications were 10.5+/-3.6 days and 11.6+/-2.5 days, and the length of hospital stays were 14.2+/-4.4 and 16.4+/-3.9 days for the treatment and control groups (NS), and the complication rates in the treatment and control groups were 10 and 40%, respectively (P<0.05). The transferrin level increased by 11.7% in the group that received glutamine-enriched TPN (P<0.05), whereas the transferrin level decreased by 12.1% in the control group (NS). At the end of the study, slight but not significant changes were determined in both groups in fasting blood sugar, albumin, blood urea nitrogen (BUN), creatinine, total cholesterol concentrations, aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, leukocytes, CD(4), CD(8), serum Zn, Ca and P levels compare to the baseline levels (NS). Significant decreases were determined in serum lipase, amylase activities and C-reactive protein (CRP) levels in both groups (P<0.05). CONCLUSIONS: The results of this study have shown that glutamine supplementation to TPN have beneficial effects on the prevention of complications in patients with AP.     

Long-term parenteral nutrition in unrestrained nonhuman primates: an experimental model

A freely mobile jacket and tether system was developed for the investigation of total parenteral nutrition (TPN)-induced metabolic bone disease and complications of prolonged TPN in 12 Macaca fascicularis nonhuman primates. The animals received TPN for 49 +/- 7 d (means +/- SEM), providing 82 +/- 2 kcal.kg-1.d-1. Serum glucose increased from 3.6 +/- 0.2 mmol/L at baseline to 8.3 +/- 1.9 mmol/L (p less than 0.01) during TPN, and serum albumin decreased from 38 +/- 1 g/L at baseline to 29 +/- 1 g/L (p less than 0.001) during 2.75% amino acid TPN and 30 +/- 2 g/L (p less than 0.01) during 5% amino acid TPN infusion. No significant changes were seen in serum prealbumin, total protein, bilirubin, alanine aminotransferase, and 5'-nucleotidase during TPN infusion. Major complications included catheter sepsis, hyperglycemia, diarrhea, and premature death in six animals. Thus, metabolic complications of prolonged TPN support may be investigated in a freely mobile nonhuman primate.     

Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition

Effects of different fatty acids on the development of hepatic steatosis were studied in rats receiving total parenteral nutrition (TPN). 65 rats, with internal jugular catheters, were divided into one control group (n = 8), and four experimental groups (n = 13-15 each). The control group was fed a chow diet and all experimental groups received TPN. TPN provided 300 kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fatty acid composition of the fat emulsion. Four kinds of fat emulsions rich in: 1) medium chain fatty acids (C8:0,C10:0), 2) oleic acid (C18:1 n-9), 3) linoleic acid (C18:2 n-6), 4) eicosapentaenoic acid (C20:5 n-3)/docosahexaenoic acid (C22:6 n-3), were used. These fat emulsions were prepared with: 1) a mixture of medium chain triglycerides (MCT) and soybean oil (9:1), 2) olive oil, 3) safflower oil, 4) fish oil, respectively. The results of the study demonstrated a higher hepatic lipid content in the olive oil and safflower oil groups than in the control group, whereas no significant difference was seen between the MCT and control groups. Also, no difference was observed between the fish oil and control groups. With regard to the plasma lipids, the MCT group and olive oil group produced hyperlipidaemia. The plasma of the safflower oil and fish oil groups, however, had a low lipid concentration comparable to the control group. These results suggest that TPN with a fat emulsion prepared with fish oil does not cause hyperlipidaemia nor induce hepatic steatosis in normal rats.     

Serum vitamin A and E concentrations in pediatric total parenteral nutrition patients

There is uncertainty as to optimal doses of fat soluble vitamins required by pediatric total parenteral nutrition (TPN) patients. We compared serum vitamin A (A) and E (E) concentrations analyzed by HPLC in chronic (greater than 2 weeks) TPN patients aged 1 month to 12 years to values obtained in out-patient surgery patients of the same age. TPN patients received 1500 micrograms of retinol and 2.5 IU of E as alpha-tocopheryl acetate (2.5 ml LyphoMed Multi Vitamin Concentrate). These doses were 214% of the recommended dose of A and 36% for E. Oral intake was minimal in most patients. The results of our study revealed a mean serum A level for TPN patients (N = 29) of 26.0 +/- 15.0 (SD) micrograms/dl vs 25.0 +/- 10.0 (SD) micrograms/dl in controls (N = 52). Mean serum E was 0.63 +/- 0.24 (SD) mg/dl vs 0.89 +/- 0.31 (SD) mg/dl for TPN patients and controls, respectively. There was no consistent trend related to duration of TPN for 23 patients with serial values. Seven (24%) TPN patients had serum A greater than mean + 2 SD of control (p less than 0.01). No values were less than mean - 2 SD. Infants on TPN had a significantly lower mean serum A (22.3 +/- 10.9 micrograms/dl) than TPN patients greater than 1 year of age (34.1 +/- 16.0 micrograms/dl; p less than 0.001). Fifty-two percent of TPN patients vs 26% of control had serum A less than 20 micrograms/dl (p greater than 0.1). For E, one patient had a high value and two patients low values relative to control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamine-enriched total parenteral nutrition maintains intestinal interleukin-4 and mucosal immunoglobulin A levels

BACKGROUND: Total parenteral nutrition (TPN) prevents progressive malnutrition but fails to maintain intestinal gut-associated lymphoid tissue (GALT) or established respiratory antiviral or antibacterial mucosal immunity. Our previous work demonstrated that decreases in intestinal immunoglobulin A (IgA) were associated with decreases in Th2-type IgA-stimulating cytokines, interleukin (IL)-4 and IL-10. Because glutamine supplementation of TPN partially preserves respiratory defenses and normalizes GALT, we investigated the ability of parenteral glutamine to normalize respiratory and intestinal IgA levels and measured Th2 cytokines in intestinal homogenates. METHODS: Animals were cannulated and randomly assigned to receive chow (n = 17), TPN (n = 18), or an isonitrogenous, isocaloric TPN solution formulated by removing the appropriate amount of amino acids and replacing them with 2% glutamine (n = 18) for 5 days. Respiratory tract and intestinal washings were obtained for IgA and the intestine homogenized and analyzed for IL-4 and IL-10. RESULTS: TPN decreased intestinal and respiratory IgA in association with decreases in intestinal IL-4 and IL-10 compared with chow-fed animals. Glutamine significantly improved respiratory and intestinal IgA levels, significantly improved IL-4 compared with TPN animals, and maintained IL-10 levels midway between chow-fed and TPN animals. CONCLUSIONS: Glutamine-enriched TPN preserved both extraintestinal and intestinal IgA levels and had a normalizing effect on Th2-type IgA-stimulating cytokines.     

Glutamine administration during total parenteral nutrition protects liver adenosine nucleotides during and after subsequent hemorrhagic shock

BACKGROUND: Glutamine supplementation of total parenteral nutrition (TPN) in stressed patients has been advocated. To determine whether glutamine supplementation affects the host response to conditions of stress, animals were given TPN with or without glutamine for 7 days. They were then subjected to the acute stress of hemorrhagic shock, which results in marked loss of hepatic adenosine triphosphate (ATP) and adenosine diphosphate (ADP), with accumulation of adenosine monophosphate (AMP) and the metabolites adenosine, inosine, hypoxanthine, and xanthine. This loss of ATP and accumulation of metabolites contributes to subsequent tissue damage. The hypothesis of the study was that glutamine supplementation would significantly improve restoration of hepatic adenosine nucleotides before and after hemorrhagic shock. METHODS: Sprague-Dawley rats were given TPN for 7 days. One half of the animals (n = 8) received TPN supplemented with glutamine, while one half received TPN with an isonitrogenous mixture of alanine and glycine. Animals were subjected to hemorrhagic shock for 30 minutes and then resuscitated using only heparinized shed blood. Liver biopsies were taken pre- and post-shock, and at 30 and 60 minutes after resuscitation. ATP, ADP, AMP, and their metabolites were measured using gradient high-performance liquid chromatography. RESULTS: After 7 days of TPN, baseline values of ATP, ADP, AMP, and metabolites were similar between the 2 groups before the initiation of shock. Glutamine-treated animals manifested a 40% decrease in ATP level immediately after shock and recovered to 90% of baseline within 60 minutes. By contrast, the control animals manifested a 66% decrease in ATP level after the shock period and recovered only to 60% of baseline at 1 hour postresuscitation. Similar changes were observed in ADP levels and were accompanied by corresponding changes in AMP and adenosine metabolites, all of which rose during shock and fell after resuscitation. CONCLUSIONS: Glutamine supplementation significantly protected the liver from tissue damage caused by hemorrhagic shock. ATP levels remained higher during shock and recovered more rapidly after resuscitation. Glutamine supplementation may help to protect cellular energy stores in the stressed organism and may offer opportunities for therapeutic intervention during and after stress.     

Effects of total parenteral nutrition on endotoxin translocation and extent of the stress response in burned rats.

Postburn endotoxin translocation has been well documented. However, the relationship between the secretion of catabolic hormones, degree of endotoxin translocation, and intestinal atrophy has not been previously demonstrated. In this experiment, modulation of the secretion of catabolic hormones according to the route of nutrient administration was examined in burned animals. A total of 55 rats, with and without a burn injury, were orally or parenterally fed. Urinary excretion of epinephrine and norepinephrine (U-EN) of each rat was measured for 48 h after burn injury as an indicator of the stress response. Evaluations of intestinal atrophy and endotoxin contents in the liver and spleen were also done 48 h after burn injury. U-EN after burn injury in rats administered total parenteral nutrition (TPN) was higher than in those fed orally. Endotoxin translocation and intestinal atrophy after thermal injury were also augmented by TPN. A significant positive correlation between U-EN and endotoxin content of the liver, and a negative correlation between U-EN and weight of the intestine, were observed. TPN enhances the stress response after burn injury. An increase in endotoxin translocation and intestinal atrophy by TPN are closely related to enhancement of the stress response.     

Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide.

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.     

合成油的营养评价——(二)合成油饲料对实验性高胆固醇血症大鼠体重、血脂和肝脂成分的影响

在88g基础饲料中加入12g不同种类的油脂(合成油、猪油和豆油)和1％胆固醇喂养大鼠5周以诱导动物产生高脂血症,并以不加入胆固醇的豆油饲料作为正常对照。比较各组动物在实验期内的生长、血清脂质、肝脏脂质和某些内脏器官重量的改变。结果如下: (1)大鼠摄食含不同油脂的致高胆固醇血症饲料5周后,各组雄鼠的体重增加无明显的不同,雌鼠的体重增加则有显著的差别,即合成油组动物的增重显著较猪油组和对照组的为低。 (2)在各种油脂饲料中加入胆固醇都可使动物的肝重增大。猪油组和豆油组动物的肝脏有明显的脂肪肝病变。肝脂含量增加,肝胆固醇和甘油三酯大量积存(分别约为对照组的9-10倍和2-3倍)。而合成油组动物的肝脏外观表现正常,肝脂含量、肝胆固醇和甘油三酯水平则接近对照组的正常水平。 (3)在各种油脂饲料中加入胆固醇喂养大鼠,对雄鼠血清胆固醇水平的影响不明显,但引起雌鼠血清胆固醇的改变和对照组比较,猪油饲料使动物的血清胆固醇含量明显增高,豆 油和合成油饲料则可维持动物的血胆固醇含量于正常水平。血清甘油三酯水平则以合成油饲料组动物的为最高。 (4)在各种饲料中加入胆固醇除增大肝脏重量外,也使雌鼠的主动脉重量增高,但饲料油脂种类对其重量的影响不明显。 上述结果表明,当饲料中含有高水?     

Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on reducing sepsis-induced liver fat deposition. Preinfusion with MCT before sepsis, however, had no effect on inflammatory-related cytokines or leukotriene in peritoneal lavage fluid. In addition, plasma arginine appears to be a more sensitive indicator than glutamine for septic insult.     

丙氨酰胺谷氨酰胺对烫伤大鼠的作用

目的研究添加丙氨酰谷氨酰胺(Ala-Gln)全胃肠外营养对烫伤大鼠的蛋白质代谢、肠粘膜形态学、创面肉芽组织的影响。方法将22只30%TBSAⅢ度烫伤SD大鼠行颈外静脉插管后,随机分为传统TPN组(传统组)和添加二肽TPN组(二伏组),每组各11例,两组接受等热量(780kg