【作者】 孟庆华；

【导师】 刘娅；

【作者基本信息】 吉林大学 ， 食品毒理学， 2009， 博士

【摘要】 本文通过对慢性肝炎、慢性重型肝炎和肝硬化患者物质能量代谢的测定,研究慢重肝患者的物质能量代谢特点;通过睡前进食的方法观察改善慢重肝患者糖代谢紊乱的可能性;应用RT-PCR及免疫组化方法研究慢重肝肝组织中部分与糖代谢相关因子的表达,探讨慢性重型肝炎患者葡萄糖代谢紊乱的发生机制。研究表明,慢重肝患者三大营养素氧化供能比例失调,能量摄入低于能量消耗,机体呈低代谢和失平衡状态,慢重肝患者的死亡发生率与能量失衡的严重程度呈正相关,即时给与低浓度的葡萄糖溶液可以改变患者的呼吸商;通过对部分慢重肝患者给予睡前进食干预措施的观察,呼吸商得到改善,碳水化合物的氧化率提高,脂肪、蛋白质分解降低,由于能量代谢的改善利于了肝细胞的修复,在一定程度上降低慢重肝患者的病死率;实验结果显示慢重肝肝组织中葡萄糖激酶mRNA和GLUT-2、GLUT-1表达减少,可见缺氧诱导因子的表达。肝脏葡萄糖激酶mRNA表达水平与葡萄糖氧化代谢障碍的严重程度呈正相关。本研究结论是,对于慢性重型肝炎患者,睡前进食一定量的碳水化合物,能够改善呼吸商和能量代谢,促进肝细胞的修复;糖代谢障碍的机制与肝脏GCK- mRNA、GLUT-2、GLUT-1表达减少及肝细胞缺氧状态密切相关。更多还原

【Abstract】 Objective:To analyze the characteristic of carbohydrate, protein, fat and energy metabolism in patients with chronic severe hepatitis; to research on the effects of a late evening snack on the Substrate and energy metabolism; to understand the mechanisms of carbohydrate metabolism disturbance in patients with chronic severe hepatitis by studying the expression of GCKmRNA and GLUT-2, HIF-1, GLUT-1 in hepatic tissues of patients with sever chronic hepatitis, to provide a theoretical basis for the individual of clinical nutritional support.Methods:Indirect calorimetry was employed to detect resting energy expenditure (REE), RQ, oxidation rates of protein (PRO), fat (FAT) and carbohydrate (CHO) in 100 cases of sever chronic hepatitis, 100 cases of liver cirrosis and 82 cases recovered from chronic viral hepatitis patients. Energy intake was determined by 1-3 days before REE measurement diet recall.30 patients with the early and middle stage of severe chronic hepatitis B were recruited and they were randomly divided into two groups, we administered an oral supplement with carbohydrate food(200kcal) to patients in study groups at before bedtime, the meal intakes were investigated and were calculated by meal expert software system at the same times; indirect calorimetry employed to detect the REE, RQ, oxidation rates of protein, fat and carbohydrate in these patients; the level of serum liver function, fasting blood glucose and PTA et were detected by Olympus640 auto analyse system, MELD scores of patients in study groups were calculated.The expression of GCK mRNA in hepatic tissues of 10 cases with sever chronic hepatitis and 10 cases with liver cirrhosis (Child-pugh A) were directed by RT-PCR technique; The expression of GLUT-2, GLUT-1 and HIF-1 in hepatic tissues of 10 cases with sever chronic hepatitis, 10 cases with liver cirrhosis, 10 cases with chronic hepatitis and 5 normal control subjects were directed by immunohistochemistry.Detection:Indirect calorimetry was employed to detect REE, RQ, oxidation rates of protein, fat and carbohydrate; the meal intakes were investigated and were calculated by meal expert software system at the same times; the level of serum liver function, fasting blood glucose and PTA et were detected by Olympus640 auto analyse system; the expression of GCK mRNA in hepatic tissues were directed by RT-PCR technique; the expression of GLUT-2 , HIF-1, GLUT-1 in hepatic tissues were directed by immunohistochemistry.Results:1. The REE of patients with sever chronic hepatitis, liver cirrhosis and chronic hepatitis were 1402.05±480.07, 1274.27±316.36 and 1396.77±384.80kcal/day, lower than the value of predicted derived from H-B equation. The RQ and the oxidation rates of carbohydrate were significantly lower in sever chronic hepatitis than that in patients with liver cirrhosis and chronic hepatitis, the oxidation rates of fat was higher(p=0.000).2. The RQ of non-survivor groups with sever chronic hepatitis was lower than the value of survivor groups, 0.81±0.07 vs 0.86±0.04, p=0.000. The oxidation rates of carbohydrate were significantly lower in non-survivor groups than that in survivor groups, the oxidation rates of fat and protein was higher(p= 0.000, 0.002, 0.009).3. The energy intakes of patients with sever chronic hepatitis, liver cirrhosis and chronic hepatitis were 1252.86±501.80 kcal/day, 1623.78±477.69 kcal/day and 1705.36±463.99 kcal/day,that was significantly lower in sever chronic hepatitis than that in patients with liver cirrhosis and chronic hepatitis(p=0.000); energy, fat and protein intakes were lower than consumption, and was a negative balance; The energy intakes were significantly higher in survivor groups with sever chronic hepatitis than in non-survivor groups.4. After a late evening snack, the carbohydrate intake in study group increased, REE has no significant change, RQ were significantly higher in study group than that in control group at the 14th day(0.87±0.07 vs 0.82±0.07,p<0.05); the oxidation rates in study and control group of protein,fat and carbohydrate were respectively 20.6±9.0 vs 28.9±11.4,30.1±20.5 vs 35.9±32.7 and 49.2±24.6 vs 37.8±30.8, the oxidation rates of protein and fat decreased and carbohydrate increased(p<0.05); ALB, PTA and FBS were significantly higher in study group than that in control group at the 14th day [(34.4±13.1 vs 30.6±9.8)g/l,(68.8±33.2 vs 38.0±29.0)%,(5.3±0.1 vs 4.3±0.2) mmol/l,p<0.05]。5. The expression level of GCK mRNA in hepatic tissues with sever chronic hepatitis was lower than with liver cirrhosis (1.13±0.11 vs 1.44±0.14,p<0.05). The level of GCK mRNA of hepatic tissues with sever chronic hepatitis had positive correlation with the oxidation rates of carbohydrate(r=0.845,P<0.01), and had no correlation with the fasting blood glucose. The expression of GLUT-2 and GLUT-1 reduced and HIF-1 was found in hepatic tissues with sever chronic hepatitis.Conclusion:1. Patients with severe chronic hepatitis are in low energy expenditure state, energy intakes and consumption was imbalance, energy was mainly supplied with fat and protein in early morning. The oxidation rates of protein and fat reduced and carbohydrate increased. Low metabolism is a self-protection of body in patients with severe chronic hepatitis.2. RQ is better than REE to reflect the body’s metabolic status of the three major nutrients and the severity of the disease.3. Oral supplementation with carbohydrate food in the patients with sever chronic hepatitis before bedtime could improve RQ, increase in glucose oxidation, decrease fat and protein catabolism.4. The level of GCK mRNA had closely relationship with the oxidation and usage of carbohydrate, the expression of HIF-1 prompt hypoxia in liver cell; the expression reduced of GCK mRNA and GLUT-2 and GLUT-1 in hepatic tissues were one of carbohydrate metabolism disturbance mechanisms in patients with chronic severe hepatitis.更多还原