發(fā)布時間：2018-05-02 04:00

  本文選題：左卡尼丁 + 炎性介質(zhì)��； 參考：《河北醫(yī)科大學》2016年碩士論文

【摘要】：目的:目前,國內(nèi)外缺乏機體代謝及炎性介質(zhì)變化方面的研究。通過研究旨在獲得給予左卡尼丁聯(lián)合營養(yǎng)支持后,重癥患者的膿毒癥及全身炎性反應綜合征的發(fā)生率的降低情況,從而減少住院費用及縮短住院時間。左旋卡尼汀是一種氨基酸衍生物,在脂肪酸(尤其是長鏈脂肪酸)的氧化代謝過程中具有重要作用。國外有研究表明,在應激情況下,尿中左旋卡尼汀的丟失量增加、血左旋卡尼汀水平降低,而補充卡尼汀能改善氮平衡�？嵬∮质侵舅岽x的必需輔助因子,它包含的卡尼汀轉(zhuǎn)位酶、乙�？嵬∞D(zhuǎn)移酶I、乙�？嵬∞D(zhuǎn)移酶II為長鏈脂肪酸轉(zhuǎn)變成乙酰卡尼汀及其轉(zhuǎn)移入線粒體所必需因子,這些物質(zhì)輕β-氧化后進行三羧酸循環(huán)唑而產(chǎn)生能量。脂肪酸氧化分三個階段:(1)活化(細胞液內(nèi)完成);(2)β氧化(線粒體內(nèi)完成);(3)三羧酸循環(huán)(線粒體完成內(nèi))�；罨A段一分子脂肪酸可被兩個高能磷酸鍵(-p)活化為脂酰-Co A。而脂酰輔酶進入線粒體三羧酸循環(huán)之前首先要被卡尼丁脂酰轉(zhuǎn)移酶催化。而機體在缺血,缺氧,應激時長鏈酰基輔酶也積累于線粒體內(nèi),同時游離卡尼丁由于大消耗而急劇減少,進一步加劇了�；鵆o A積累。缺血,缺氧時ATP水平下降,亞細胞膜和膜通透性增加,總脂酰輔酶A堆積可導致在膜相崩解,細胞結(jié)構在變化中引起細胞死亡。此外,低氧狀態(tài)下糖的無氧酵解增強,脂肪酸積累導致酸中毒,進一步加速細胞死亡自溶。足夠劑量的血游離卡尼丁可以使累積的脂肪�；o酶A進入線粒體,降低其腺嘌呤核苷酸轉(zhuǎn)位酶的抑制,從而使氧化磷酸化得以順利進行,左卡尼丁參與的脂肪酸氧化供能可直接供給如心肌細胞、腦細胞、骨骼細胞等組織細胞中。左卡尼丁可以增加細胞色素氧化酶,NADH色素C還原酶的活性,加速ATP產(chǎn)生,參與某些藥物的解毒作用。左-卡尼汀通過能量產(chǎn)生而提高組織器官的功能,減輕組織缺血缺氧狀態(tài)。左卡尼汀的其他功能有:中長鏈脂肪酸的二次氧化,對結(jié)合輔酶、游離輔酶的組合比率作為緩沖,從氨基酸(包括支鏈氨基酸)中產(chǎn)生能量,調(diào)節(jié)血液中氨的濃度。腫瘤根治術后急危重癥患者體內(nèi)IL-1,IL-6是中性粒細胞最有效和主要驅(qū)化劑,最新文獻報道,IL-6的表達高峰是在炎癥高峰期,在危重癥患者創(chuàng)傷早期血清中檢測TNF-αIL-1 IL-6較正常情況下高3-6倍,且高炎性介質(zhì)水平可引發(fā)或加重全身炎性反應綜合征(SIRS),左卡尼丁注射液是膿毒癥患者脂肪代謝過程的有益補充。為維持體內(nèi)卡尼汀水平,減少蛋白質(zhì)分解,改善炎性介質(zhì)水平,我們選用(瑞陽制藥有限公司生產(chǎn))的卡尼汀注射液(Carnitine)聯(lián)合腸外營養(yǎng)對我院ICU消化系統(tǒng)腫瘤根治術后的患者研究患者炎性因子水平變化進行研究。通過研究旨在獲得給予左卡尼丁聯(lián)合營養(yǎng)支持后,重癥患者的膿毒癥及全身炎性反應綜合征的發(fā)生率的降低情況,從而減少住院費用及縮短住院時間。方法:1研究對象與抽樣以保定市第一中心醫(yī)院同期入重癥醫(yī)學科,消化系統(tǒng)腫瘤根治手術且腸外營養(yǎng)支持大于7天患者為研究對象,跟蹤患者至腫瘤外科、胃腸外科及普通外科康復治療全過程的研究。入選標準1)消化道腫瘤常規(guī)根治手術后2)年齡18—70歲3)消化道腫瘤術后TPN至少7天排除標準1)糖尿病需口服或注射降糖藥物2)脂質(zhì)代謝障礙需藥物治療(甘油三脂200mg/dl,或膽固醇240mg/dl)3)腎功能異常(血清肌酐CR1.6mg/dl或BUN30mg/dl)4)肝功能異常(ALT60U/L或血清總膽紅素1.2mg/dl)5)未控制的內(nèi)分泌系統(tǒng)疾病,如腎上腺皮質(zhì)功能亢進、甲亢以及使用甲狀腺素、皮質(zhì)激素或其他免疫調(diào)節(jié)劑治療的患者6)術后10天之內(nèi)即進行放化療的患者7)在過去的六個月內(nèi)濫用和/或依賴藥物和/或麻醉劑,嗜酒。8)術中輸血量超過1000ml按照入組及排除標準,對患者行NRS2002+SGA營養(yǎng)評價法,抽取60例研究樣本,隨機分為兩組,實驗組30例,對照組30例。2方法實驗組:自術后第一天(POD+1)腸外營養(yǎng)液中按計劃:加入Carniti ne 40mg/公斤體重/天,共輸入7天。對照組:POD+1營養(yǎng)液中使用同樣包裝的安慰劑40mg/公斤體重/天。(誤差不超過5%),兩組的主要能量和氮量同等(熱卡30kcal/kg/d,蛋白質(zhì)1.0g/kg/d)。實驗組及對照組均為等熱量、等氮量攝入,醫(yī)生將營養(yǎng)用藥處方每天上午8點30分前交給配液中心的高年資配液護士(相當于控制員)。營養(yǎng)液按操作規(guī)范在1000級潔凈度的層流室內(nèi)的100級潔凈臺內(nèi)進行“全合一”(AIO)混合配置。每天上午10點前交給病房。本次研究于患者術后第7天給予序貫性腸內(nèi)營養(yǎng)支持,并逐步替代腸外營養(yǎng)支持。3觀察指標手術當日、入組治療(術后)7天血漿C反應蛋白CRP,白細胞介素1,IL-1,白細胞介素6 IL-6,腫瘤壞死因子TNF-α,膽固醇TC,三酰甘油T G,低密度脂蛋白LDL-C,高密度脂蛋白HDL-C,結(jié)合卡尼丁濃度TC,游離卡尼汀濃度FC。4統(tǒng)計學方法采用統(tǒng)計軟件Stat View(SAS,Institute Inc.SAS Campus Drive,Cary,NC 27513,USA.Series no STV 04171),進行數(shù)據(jù)分析。正態(tài)數(shù)據(jù)采用ANOVA分析,非正態(tài)數(shù)據(jù)采用Willcoxon分析,率的分析用χ2檢驗,數(shù)據(jù)以均數(shù)±標準差(x±s)表示,P0.05為差異有統(tǒng)計學意義。結(jié)果:在消化道腫瘤根治術后,IL-1、IL-6、TNF-α是SIRS發(fā)生的重要炎癥介質(zhì),而手術創(chuàng)傷及應激反應可引起以上炎癥介質(zhì)的釋放,進而抑制胃腸動力。1卡尼丁聯(lián)合腸外營養(yǎng)支持實驗組的炎性因子水平下降程度(97.7%)明顯高于對照組(41.6%)。并且,術后第7天檢測血清L-1、IL-6、TNF-α表達水平在試驗組和對照組中的表達分別為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觀察結(jié)果顯示:脂蛋白治療前的比較兩組患者TC、TG、L-DLC和H-DLC水平無差異,對照組治療后各項指標與治療前比較無統(tǒng)計學意義(P0.05),實驗組治療后TC、TG、L-DLC和H-DLC較治療前無明顯變化,差異無統(tǒng)計學意義(P0.05),3血中卡尼汀濃度實驗結(jié)果顯示,治療前實驗組和對照組對比無統(tǒng)計學差異,而實驗組、對照組治療前后總卡尼丁濃度、游離卡尼丁濃度均出現(xiàn)不同程度下降,實驗組下降幅度及對照組下降幅度兩者對比,具有明顯差異,具有統(tǒng)計學意義(P0.05),4實驗組的患者治療方案均未發(fā)生肝臟功能異常,對照組肝臟功能異常3例(通過應用保肝藥物易善復多烯磷脂酰膽堿注射液后將至正常),其中2例谷丙轉(zhuǎn)氨酶60u/L,1例80u/L。兩組無一例嚴重感染并發(fā)癥發(fā)生。通過對比肝功能異常發(fā)生率,實驗組及對照組無統(tǒng)計學意義(P0.05)。結(jié)論:通過實驗組與對照組的對比分析,按計劃完成了對60例消化道腫瘤術后患者的臨床觀察結(jié)果。我們進行了術后炎性因子水平、術后住院日、感染相關并發(fā)癥、營養(yǎng)費用、營養(yǎng)指標和住院總費用及體液細胞免疫指標的研究觀察。結(jié)果顯示:左卡尼丁強化胃腸外營養(yǎng)在消化道腫瘤術后患者應用能明顯降低患者炎性介質(zhì)水平P0.05。實驗組的患者治療方案均未發(fā)生臟器功能的損壞,對照組有肝臟功能異常3例(通過應用保肝藥物易善復多烯磷脂酰膽堿注射液后將至正常),左卡尼丁強化腸外營養(yǎng)對患者肝臟功能較單純腸外營養(yǎng)支持無差異。消化道腫瘤術后患者會造成體內(nèi)T C、FC水平下降,左卡尼丁強化腸外營養(yǎng)支持是外源性補充的重要手段,能夠明顯改善患者血中TC、FC水平。短期靜脈實施左卡尼丁強化腸外營養(yǎng)對患者血脂水平無影響。消化道腫瘤術后患者對富含肉堿食物攝入量的減少是造成患者脂肪酸代謝異常并成為導致SIRS、營養(yǎng)不良等并發(fā)癥發(fā)生的因素之一。這對于抑制消化道腫瘤手術后患者高炎性反應可能有益。
[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.

【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R735

【參考文獻】

中國期刊全文數(shù)據(jù)庫 前5條

1 Cuneyt Kayaalp;;Bursectomy at radical gastrectomy[J];World Journal of Gastrointestinal Surgery;2015年10期

2 譚鶴長;宋雪霞;劉春曉;;左卡尼汀改善維持性血液透析患者微炎癥狀態(tài)的療效觀察[J];臨床醫(yī)學工程;2014年11期

3 王爭;陳錦先;王平治;;復方支鏈氨基酸注射液對結(jié)直腸癌根治術后患者的營養(yǎng)支持作用[J];中華胃腸外科雜志;2006年05期

4 宋京翔,卿三華,黃祥成,齊德林;精氨酸增強的胃腸外營養(yǎng)對結(jié)直腸癌患者術后免疫功能的影響[J];第一軍醫(yī)大學學報;2002年06期

5 李維勤,李寧;外科病人的代謝改變和圍手術期營養(yǎng)支持[J];中國實用外科雜志;2001年07期

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