左卡尼汀联合肠外营养对消化道肿瘤根治术后重症患者炎性因子的影响

发布时间：2018-05-02 04:00

  本文选题：左卡尼丁 + 炎性介质　； 参考：《河北医科大学》2016年硕士论文

【摘要】：目的:目前,国内外缺乏机体代谢及炎性介质变化方面的研究。通过研究旨在获得给予左卡尼丁联合营养支持后,重症患者的脓毒症及全身炎性反应综合征的发生率的降低情况,从而减少住院费用及缩短住院时间。左旋卡尼汀是一种氨基酸衍生物,在脂肪酸(尤其是长链脂肪酸)的氧化代谢过程中具有重要作用。国外有研究表明,在应激情况下,尿中左旋卡尼汀的丢失量增加、血左旋卡尼汀水平降低,而补充卡尼汀能改善氮平衡。卡尼汀又是脂肪酸代谢的必需辅助因子,它包含的卡尼汀转位酶、乙酰卡尼汀转移酶I、乙酰卡尼汀转移酶II为长链脂肪酸转变成乙酰卡尼汀及其转移入线粒体所必需因子,这些物质轻β-氧化后进行三羧酸循环唑而产生能量。脂肪酸氧化分三个阶段:(1)活化(细胞液内完成);(2)β氧化(线粒体内完成);(3)三羧酸循环(线粒体完成内)。活化阶段一分子脂肪酸可被两个高能磷酸键(-p)活化为脂酰-Co A。而脂酰辅酶进入线粒体三羧酸循环之前首先要被卡尼丁脂酰转移酶催化。而机体在缺血,缺氧,应激时长链酰基辅酶也积累于线粒体内,同时游离卡尼丁由于大消耗而急剧减少,进一步加剧了酰基Co A积累。缺血,缺氧时ATP水平下降,亚细胞膜和膜通透性增加,总脂酰辅酶A堆积可导致在膜相崩解,细胞结构在变化中引起细胞死亡。此外,低氧状态下糖的无氧酵解增强,脂肪酸积累导致酸中毒,进一步加速细胞死亡自溶。足够剂量的血游离卡尼丁可以使累积的脂肪酰基辅酶A进入线粒体,降低其腺嘌呤核苷酸转位酶的抑制,从而使氧化磷酸化得以顺利进行,左卡尼丁参与的脂肪酸氧化供能可直接供给如心肌细胞、脑细胞、骨骼细胞等组织细胞中。左卡尼丁可以增加细胞色素氧化酶,NADH色素C还原酶的活性,加速ATP产生,参与某些药物的解毒作用。左-卡尼汀通过能量产生而提高组织器官的功能,减轻组织缺血缺氧状态。左卡尼汀的其他功能有:中长链脂肪酸的二次氧化,对结合辅酶、游离辅酶的组合比率作为缓冲,从氨基酸(包括支链氨基酸)中产生能量,调节血液中氨的浓度。肿瘤根治术后急危重症患者体内IL-1,IL-6是中性粒细胞最有效和主要驱化剂,最新文献报道,IL-6的表达高峰是在炎症高峰期,在危重症患者创伤早期血清中检测TNF-αIL-1 IL-6较正常情况下高3-6倍,且高炎性介质水平可引发或加重全身炎性反应综合征(SIRS),左卡尼丁注射液是脓毒症患者脂肪代谢过程的有益补充。为维持体内卡尼汀水平,减少蛋白质分解,改善炎性介质水平,我们选用(瑞阳制药有限公司生产)的卡尼汀注射液(Carnitine)联合肠外营养对我院ICU消化系统肿瘤根治术后的患者研究患者炎性因子水平变化进行研究。通过研究旨在获得给予左卡尼丁联合营养支持后,重症患者的脓毒症及全身炎性反应综合征的发生率的降低情况,从而减少住院费用及缩短住院时间。方法:1研究对象与抽样以保定市第一中心医院同期入重症医学科,消化系统肿瘤根治手术且肠外营养支持大于7天患者为研究对象,跟踪患者至肿瘤外科、胃肠外科及普通外科康复治疗全过程的研究。入选标准1)消化道肿瘤常规根治手术后2)年龄18—70岁3)消化道肿瘤术后TPN至少7天排除标准1)糖尿病需口服或注射降糖药物2)脂质代谢障碍需药物治疗(甘油三脂200mg/dl,或胆固醇240mg/dl)3)肾功能异常(血清肌酐CR1.6mg/dl或BUN30mg/dl)4)肝功能异常(ALT60U/L或血清总胆红素1.2mg/dl)5)未控制的内分泌系统疾病,如肾上腺皮质功能亢进、甲亢以及使用甲状腺素、皮质激素或其他免疫调节剂治疗的患者6)术后10天之内即进行放化疗的患者7)在过去的六个月内滥用和/或依赖药物和/或麻醉剂,嗜酒。8)术中输血量超过1000ml按照入组及排除标准,对患者行NRS2002+SGA营养评价法,抽取60例研究样本,随机分为两组,实验组30例,对照组30例。2方法实验组:自术后第一天(POD+1)肠外营养液中按计划:加入Carniti ne 40mg/公斤体重/天,共输入7天。对照组:POD+1营养液中使用同样包装的安慰剂40mg/公斤体重/天。(误差不超过5%),两组的主要能量和氮量同等(热卡30kcal/kg/d,蛋白质1.0g/kg/d)。实验组及对照组均为等热量、等氮量摄入,医生将营养用药处方每天上午8点30分前交给配液中心的高年资配液护士(相当于控制员)。营养液按操作规范在1000级洁净度的层流室内的100级洁净台内进行“全合一”(AIO)混合配置。每天上午10点前交给病房。本次研究于患者术后第7天给予序贯性肠内营养支持,并逐步替代肠外营养支持。3观察指标手术当日、入组治疗(术后)7天血浆C反应蛋白CRP,白细胞介素1,IL-1,白细胞介素6 IL-6,肿瘤坏死因子TNF-α,胆固醇TC,三酰甘油T G,低密度脂蛋白LDL-C,高密度脂蛋白HDL-C,结合卡尼丁浓度TC,游离卡尼汀浓度FC。4统计学方法采用统计软件Stat View(SAS,Institute Inc.SAS Campus Drive,Cary,NC 27513,USA.Series no STV 04171),进行数据分析。正态数据采用ANOVA分析,非正态数据采用Willcoxon分析,率的分析用χ2检验,数据以均数±标准差(x±s)表示,P0.05为差异有统计学意义。结果:在消化道肿瘤根治术后,IL-1、IL-6、TNF-α是SIRS发生的重要炎症介质,而手术创伤及应激反应可引起以上炎症介质的释放,进而抑制胃肠动力。1卡尼丁联合肠外营养支持实验组的炎性因子水平下降程度(97.7%)明显高于对照组(41.6%)。并且,术后第7天检测血清L-1、IL-6、TNF-α表达水平在试验组和对照组中的表达分别为41.17±10.36pg/l69.65±13.12pg/l,31.21±9.74pg/l 56.36±6.18pg/l,19.35±8.12 pg/l24.48±10.01 pg/l。2 TC、TG、H-DLC、L-DLC观察结果显示:脂蛋白治疗前的比较两组患者TC、TG、L-DLC和H-DLC水平无差异,对照组治疗后各项指标与治疗前比较无统计学意义(P0.05),实验组治疗后TC、TG、L-DLC和H-DLC较治疗前无明显变化,差异无统计学意义(P0.05),3血中卡尼汀浓度实验结果显示,治疗前实验组和对照组对比无统计学差异,而实验组、对照组治疗前后总卡尼丁浓度、游离卡尼丁浓度均出现不同程度下降,实验组下降幅度及对照组下降幅度两者对比,具有明显差异,具有统计学意义(P0.05),4实验组的患者治疗方案均未发生肝脏功能异常,对照组肝脏功能异常3例(通过应用保肝药物易善复多烯磷脂酰胆碱注射液后将至正常),其中2例谷丙转氨酶60u/L,1例80u/L。两组无一例严重感染并发症发生。通过对比肝功能异常发生率,实验组及对照组无统计学意义(P0.05)。结论:通过实验组与对照组的对比分析,按计划完成了对60例消化道肿瘤术后患者的临床观察结果。我们进行了术后炎性因子水平、术后住院日、感染相关并发症、营养费用、营养指标和住院总费用及体液细胞免疫指标的研究观察。结果显示:左卡尼丁强化胃肠外营养在消化道肿瘤术后患者应用能明显降低患者炎性介质水平P0.05。实验组的患者治疗方案均未发生脏器功能的损坏,对照组有肝脏功能异常3例(通过应用保肝药物易善复多烯磷脂酰胆碱注射液后将至正常),左卡尼丁强化肠外营养对患者肝脏功能较单纯肠外营养支持无差异。消化道肿瘤术后患者会造成体内T C、FC水平下降,左卡尼丁强化肠外营养支持是外源性补充的重要手段,能够明显改善患者血中TC、FC水平。短期静脉实施左卡尼丁强化肠外营养对患者血脂水平无影响。消化道肿瘤术后患者对富含肉碱食物摄入量的减少是造成患者脂肪酸代谢异常并成为导致SIRS、营养不良等并发症发生的因素之一。这对于抑制消化道肿瘤手术后患者高炎性反应可能有益。
[Abstract]:Objective: to present a study on the lack of metabolic and inflammatory mediators at home and abroad. The purpose of this study is to reduce the incidence of sepsis and systemic inflammatory response syndrome in severe patients after the study of Levocarnitin combined with nutritional support to reduce hospitalization costs and shorten hospitalization. L-carnitine is a kind of ammonia. Basic acid derivatives play an important role in the oxidative metabolism of fatty acids, especially long chain fatty acids. Studies abroad have shown that the loss of Levocarnitine in urine increases and blood levocarnitine levels decrease under stress conditions, while supplementation with carnitine can improve the nitrogen balance. It contains carnitine transposition enzyme, acetylcarnitine transferase I, acetylcarnitine transferase II transformation into acetyl carnitine and its transfer into mitochondria, and these substances light beta - oxidized to produce three carboxyl circulating azole and produce energy. Fatty acid oxidation is divided into three stages: (1) activation (2) beta (2) beta Oxidation (complete mitochondria); (3) the three carboxylic acid cycle (mitochondria complete). The activation phase of a molecular fatty acid can be activated by two high-energy phosphate bonds (-p) to be activated by the lipoyl -Co A. and the lipoyl coenzyme is first catalyzed by Kanitin lipoyl transferase before entering the mitochondrial three carboxylic acid cycle. The body is in the ischemia, anoxia, and stress, and the long chain acyl coenzyme is also Accumulation in mitochondria, while free carnitin decreased rapidly due to large consumption, further aggravated acyl Co A accumulation. Ischemia, anoxia, ATP level decreased, subcellular membrane and membrane permeability increased, total lipoyl coenzyme A accumulation could cause disintegration in membrane phase, cell structure caused cell death in changes. In addition, oxygen free oxygen in the state of oxygen Glycolysis increases, fatty acid accumulation causes acidosis and further accelerates cell death autolysis. Sufficient dose of blood free Kanitin can make the cumulative fatty acyl coenzyme A into mitochondria and reduce the inhibition of its adenine nucleotide transposition enzyme, thereby enabling oxidative phosphorylation to proceed smoothly, and the left Kanitin participates in the oxidation of fatty acids available. In the direct supply of tissue cells such as cardiomyocytes, brain cells, and bone cells. Levocarnitin can increase the activity of cytochrome oxidase, NADH pigment C reductase, accelerate the production of ATP, and participate in the detoxification of some drugs. Leo carnitine improves the function of the tissue organ by generating energy and reduces the state of tissue ischemia and hypoxia. Left Carney Other functions are: two oxidation of medium long chain fatty acids, a combination of coenzyme and free coenzyme as a buffer, energy from amino acids (including branched chain amino acids) to regulate the concentration of ammonia in the blood. IL-1, IL-6, is the most effective and major agent of neutrophils in patients with acute and critical diseases after radical resection. It is reported that the peak of expression of IL-6 is at the peak of inflammation, and the serum level of TNF- alpha IL-1 IL-6 is 3-6 times higher than normal in the early stage of trauma, and the level of high inflammatory mediators can cause or aggravate the systemic inflammatory response syndrome (SIRS). The left carnitin injection is a beneficial supplement to the lipid metabolism in patients with sepsis. Carnitine level in vivo, reducing protein decomposition and improving the level of inflammatory mediators, we selected the carnitine injection (Carnitine) combined with parenteral parenteral nutrition to study the changes in the level of inflammatory factors in patients after radical resection of ICU digestive system. The incidence of sepsis and systemic inflammatory response syndrome in severe patients was reduced after neidine combined with nutritional support, thus reducing hospitalization costs and shortening the duration of hospitalization. Methods: 1 subjects and samples were sampled at the Baoding First Central Hospital in the same period of severe medicine, digestive system tumor radical surgery and parenteral nutrition support greater than 7 A study of patients, tracking patients to tumor surgery, gastrointestinal surgery and general surgical rehabilitation. Standard 1) 1) after routine radical resection of digestive tract tumors, 2) age 18 to 70 years, 3) digestive tract tumors, at least 7 days after surgery for 7 days, 1) diabetes needs oral or injection hypoglycemic drugs 2) lipid metabolism disorder needs drugs Treatment (glycerol three fat 200mg/dl, or cholesterol 240mg/dl) 3) abnormal renal function (serum creatinine CR1.6mg/dl or BUN30mg/dl) 4) abnormal liver function (ALT60U/L or serum total bilirubin 1.2mg/dl) 5) uncontrolled endocrine system diseases such as hyperfunction of adrenal cortex, hyperthyroidism, thyroxine, corticosteroids, or other immunomodulators Patients 6) in the 10 days after operation, 7 of patients undergoing chemotherapy were abused and / or dependent on drugs and / or anesthetics in the past six months. The amount of blood transfusion in alcoholic.8 was more than 1000ml in accordance with the entry group and the exclusion criteria, and the patients were divided into two groups, 30 in the experimental group and 30 in the control group by NRS2002+SGA nutrition evaluation. The 2 method experiment group: the first day (POD+1) parenteral nutrient solution from the first day after the operation was planned: Carniti ne 40mg/ kg body weight / day for a total of 7 days. In the control group, the same package of placebo 40mg/ kg body weight / day was used in the POD+1 nutrient solution. (the error was not more than 5%), the two groups of main energy and nitrogen were equal (heat card 30kcal/kg/d, protein 1.0g/kg/d). The experimental group and the control group were equal calorie, equal to nitrogen intake, the doctor put the prescription of the prescription of the nutrition medication before 8:30 every day before 8:30 a.m. to the nurse (equivalent to the controller). The nutrient solution was mixed in the 100 level clean table in the 1000 level cleanliness of the laminar cleanliness. 10 a.m. every day. The study was given to the ward. This study was given sequential enteral nutrition support seventh days after the operation, and gradually replaced parenteral nutrition support.3 on the day of surgery, and the plasma C reactive protein CRP, interleukin 1, IL-1, interleukin 6 IL-6, tumor necrosis factor TNF- alpha, cholesterol TC, three acylglycerol T G, low density, low density in the group treatment (postoperative). Degree lipoprotein LDL-C, high density lipoprotein HDL-C, combined with carnitin concentration TC, free carnitine concentration FC.4 statistics method using statistical software Stat View (SAS, Institute Inc.SAS Campus Drive, Cary, 27513, 04171) to carry out data analysis. The analysis was carried out by the chi square test (x + s), and the data were indicated by mean mean standard deviation (x + s). Results: after the radical operation of digestive tract tumor, IL-1, IL-6, TNF- alpha were important inflammatory mediators of SIRS, and the surgical trauma and stress response could cause the release of the above inflammatory mediators, and then the gastrointestinal motility.1 carnitin combined with the outside of the intestines. The level of inflammatory factors decreased (97.7%) in the experimental group (97.7%) was significantly higher than that in the control group (41.6%). And the expression level of serum L-1, IL-6, TNF- alpha in the test group and the control group was 41.17 + 10.36pg/l69.65 + 13.12pg/l, 31.21 + 9.74pg/l 56.36 + 6.18pg/l, 19.35 + 8.12 pg/l24.48 + 10.01 pg/l.2 TC, T, after the operation. The results of G, H-DLC and L-DLC showed that there was no difference in the levels of TC, TG, L-DLC and H-DLC in the two groups before the treatment of lipoprotein, and there was no significant difference between the control group after treatment and before treatment (P0.05). There was no significant difference in TC, TG, L-DLC and H-DLC before treatment in the experimental group. There was no significant difference in the concentration of carnitine in the 3 blood. The results showed that there was no statistical difference between the experimental group and the control group before and after treatment, but the concentration of total carnitin and the concentration of free carnitin decreased in the experimental group before and after the treatment. The decrease of the experimental group and the decrease of the control group were compared, with significant difference (P0.05). The 4 experimental group had a significant difference. There were no abnormal liver function in the treatment regimen, and 3 cases of abnormal liver function in the control group (after the application of the liver protective drug easily to Polyene Phosphatidylcholine Injection after Polyene Phosphatidylcholine Injection), 2 cases of alanine aminotransferase 60u/L and 1 cases of 80u/L. two had no serious infection complications. There was no statistical significance (P0.05). Conclusion: the results of clinical observation of 60 patients with digestive tract tumor were completed by the comparison and analysis between the experimental group and the control group. We performed the postoperative inflammatory factors, postoperative hospital stay, infection related complications, nutritional costs, nutritional indicators, total hospitalization expenses and humoral cell immunity. The results showed that the use of leachnitin enhanced parenteral parenteral nutrition in the patients with digestive tract tumor can significantly reduce the level of inflammatory mediators in the patients with P0.05. experimental group. There were no damage to the viscera function in the treatment regimen of the patients in the P0.05. experimental group, and the control group had liver function abnormality (through the application of the liver protective drug to polyene phosphatidylcholine. After the injection, there is no difference between Zo C Nitin's parenteral nutrition and parenteral nutrition. The patients with digestive tract tumor will cause T C, FC level decrease, and Zo C Nitin enhanced parenteral nutrition support is an important means of exogenous supplement, which can obviously improve the level of TC and FC in the blood of the patients. The implementation of lephonidin enhanced parenteral nutrition has no effect on blood lipid levels in patients. The decrease in the intake of carnitine rich food after digestive tract cancer is one of the factors that cause complications such as SIRS, malnutrition and other complications. It's good.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735

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