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

【摘要】：目的:目前,國(guó)內(nèi)外缺乏機(jī)體代謝及炎性介質(zhì)變化方面的研究。通過(guò)研究旨在獲得給予左卡尼丁聯(lián)合營(yíng)養(yǎng)支持后,重癥患者的膿毒癥及全身炎性反應(yīng)綜合征的發(fā)生率的降低情況,從而減少住院費(fèi)用及縮短住院時(shí)間。左旋卡尼汀是一種氨基酸衍生物,在脂肪酸(尤其是長(zhǎng)鏈脂肪酸)的氧化代謝過(guò)程中具有重要作用。國(guó)外有研究表明,在應(yīng)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(bǔ)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、乙酰卡尼汀轉(zhuǎn)移酶II為長(zhǎng)鏈脂肪酸轉(zhuǎn)變成乙�？嵬〖捌滢D(zhuǎn)移入線粒體所必需因子,這些物質(zhì)輕β-氧化后進(jìn)行三羧酸循環(huán)唑而產(chǎn)生能量。脂肪酸氧化分三個(gè)階段:(1)活化(細(xì)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(gè)高能磷酸鍵(-p)活化為脂酰-Co A。而脂酰輔酶進(jìn)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(jī)體在缺血,缺氧,應(yīng)激時(shí)長(zhǎng)鏈�；o酶也積累于線粒體內(nèi),同時(shí)游離卡尼丁由于大消耗而急劇減少,進(jìn)一步加劇了�；鵆o A積累。缺血,缺氧時(shí)ATP水平下降,亞細(xì)胞膜和膜通透性增加,總脂酰輔酶A堆積可導(dǎo)致在膜相崩解,細(xì)胞結(jié)構(gòu)在變化中引起細(xì)胞死亡。此外,低氧狀態(tài)下糖的無(wú)氧酵解增強(qiáng),脂肪酸積累導(dǎo)致酸中毒,進(jìn)一步加速細(xì)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(jìn)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(jìn)行,左卡尼丁參與的脂肪酸氧化供能可直接供給如心肌細(xì)胞、腦細(xì)胞、骨骼細(xì)胞等組織細(xì)胞中。左卡尼丁可以增加細(xì)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(guò)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(zhǎng)鏈脂肪酸的二次氧化,對(duì)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(shù)后急危重癥患者體內(nèi)IL-1,IL-6是中性粒細(xì)胞最有效和主要驅(qū)化劑,最新文獻(xiàn)報(bào)道,IL-6的表達(dá)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(cè)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(yīng)綜合征(SIRS),左卡尼丁注射液是膿毒癥患者脂肪代謝過(guò)程的有益補(bǔ)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(yáng)制藥有限公司生產(chǎn))的卡尼汀注射液(Carnitine)聯(lián)合腸外營(yíng)養(yǎng)對(duì)我院ICU消化系統(tǒng)腫瘤根治術(shù)后的患者研究患者炎性因子水平變化進(jìn)行研究。通過(guò)研究旨在獲得給予左卡尼丁聯(lián)合營(yíng)養(yǎng)支持后,重癥患者的膿毒癥及全身炎性反應(yīng)綜合征的發(fā)生率的降低情況,從而減少住院費(fèi)用及縮短住院時(shí)間。方法:1研究對(duì)象與抽樣以保定市第一中心醫(yī)院同期入重癥醫(yī)學(xué)科,消化系統(tǒng)腫瘤根治手術(shù)且腸外營(yíng)養(yǎng)支持大于7天患者為研究對(duì)象,跟蹤患者至腫瘤外科、胃腸外科及普通外科康復(fù)治療全過(guò)程的研究。入選標(biāo)準(zhǔn)1)消化道腫瘤常規(guī)根治手術(shù)后2)年齡18—70歲3)消化道腫瘤術(shù)后TPN至少7天排除標(biāo)準(zhǔn)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(jìn)、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(shù)后10天之內(nèi)即進(jìn)行放化療的患者7)在過(guò)去的六個(gè)月內(nèi)濫用和/或依賴藥物和/或麻醉劑,嗜酒。8)術(shù)中輸血量超過(guò)1000ml按照入組及排除標(biāo)準(zhǔn),對(duì)患者行NRS2002+SGA營(yíng)養(yǎng)評(píng)價(jià)法,抽取60例研究樣本,隨機(jī)分為兩組,實(shí)驗(yàn)組30例,對(duì)照組30例。2方法實(shí)驗(yàn)組:自術(shù)后第一天(POD+1)腸外營(yíng)養(yǎng)液中按計(jì)劃:加入Carniti ne 40mg/公斤體重/天,共輸入7天。對(duì)照組:POD+1營(yíng)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(guò)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(shí)驗(yàn)組及對(duì)照組均為等熱量、等氮量攝入,醫(yī)生將營(yíng)養(yǎng)用藥處方每天上午8點(diǎn)30分前交給配液中心的高年資配液護(hù)士(相當(dāng)于控制員)。營(yíng)養(yǎng)液按操作規(guī)范在1000級(jí)潔凈度的層流室內(nèi)的100級(jí)潔凈臺(tái)內(nèi)進(jìn)行“全合一”(AIO)混合配置。每天上午10點(diǎn)前交給病房。本次研究于患者術(shù)后第7天給予序貫性腸內(nèi)營(yíng)養(yǎng)支持,并逐步替代腸外營(yíng)養(yǎng)支持。3觀察指標(biāo)手術(shù)當(dāng)日、入組治療(術(shù)后)7天血漿C反應(yīng)蛋白CRP,白細(xì)胞介素1,IL-1,白細(xì)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(jì)學(xué)方法采用統(tǒng)計(jì)軟件Stat View(SAS,Institute Inc.SAS Campus Drive,Cary,NC 27513,USA.Series no STV 04171),進(jìn)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(yàn),數(shù)據(jù)以均數(shù)±標(biāo)準(zhǔn)差(x±s)表示,P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:在消化道腫瘤根治術(shù)后,IL-1、IL-6、TNF-α是SIRS發(fā)生的重要炎癥介質(zhì),而手術(shù)創(chuàng)傷及應(yīng)激反應(yīng)可引起以上炎癥介質(zhì)的釋放,進(jìn)而抑制胃腸動(dòng)力。1卡尼丁聯(lián)合腸外營(yíng)養(yǎng)支持實(shí)驗(yàn)組的炎性因子水平下降程度(97.7%)明顯高于對(duì)照組(41.6%)。并且,術(shù)后第7天檢測(cè)血清L-1、IL-6、TNF-α表達(dá)水平在試驗(yàn)組和對(duì)照組中的表達(dá)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(wú)差異,對(duì)照組治療后各項(xiàng)指標(biāo)與治療前比較無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),實(shí)驗(yàn)組治療后TC、TG、L-DLC和H-DLC較治療前無(wú)明顯變化,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),3血中卡尼汀濃度實(shí)驗(yàn)結(jié)果顯示,治療前實(shí)驗(yàn)組和對(duì)照組對(duì)比無(wú)統(tǒng)計(jì)學(xué)差異,而實(shí)驗(yàn)組、對(duì)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(shí)驗(yàn)組下降幅度及對(duì)照組下降幅度兩者對(duì)比,具有明顯差異,具有統(tǒng)計(jì)學(xué)意義(P0.05),4實(shí)驗(yàn)組的患者治療方案均未發(fā)生肝臟功能異常,對(duì)照組肝臟功能異常3例(通過(guò)應(yīng)用保肝藥物易善復(fù)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(wú)一例嚴(yán)重感染并發(fā)癥發(fā)生。通過(guò)對(duì)比肝功能異常發(fā)生率,實(shí)驗(yàn)組及對(duì)照組無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:通過(guò)實(shí)驗(yàn)組與對(duì)照組的對(duì)比分析,按計(jì)劃完成了對(duì)60例消化道腫瘤術(shù)后患者的臨床觀察結(jié)果。我們進(jìn)行了術(shù)后炎性因子水平、術(shù)后住院日、感染相關(guān)并發(fā)癥、營(yíng)養(yǎng)費(fèi)用、營(yíng)養(yǎng)指標(biāo)和住院總費(fèi)用及體液細(xì)胞免疫指標(biāo)的研究觀察。結(jié)果顯示:左卡尼丁強(qiáng)化胃腸外營(yíng)養(yǎng)在消化道腫瘤術(shù)后患者應(yīng)用能明顯降低患者炎性介質(zhì)水平P0.05。實(shí)驗(yàn)組的患者治療方案均未發(fā)生臟器功能的損壞,對(duì)照組有肝臟功能異常3例(通過(guò)應(yīng)用保肝藥物易善復(fù)多烯磷脂酰膽堿注射液后將至正常),左卡尼丁強(qiáng)化腸外營(yíng)養(yǎng)對(duì)患者肝臟功能較單純腸外營(yíng)養(yǎng)支持無(wú)差異。消化道腫瘤術(shù)后患者會(huì)造成體內(nèi)T C、FC水平下降,左卡尼丁強(qiáng)化腸外營(yíng)養(yǎng)支持是外源性補(bǔ)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(shí)施左卡尼丁強(qiáng)化腸外營(yíng)養(yǎng)對(duì)患者血脂水平無(wú)影響。消化道腫瘤術(shù)后患者對(duì)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(dǎo)致SIRS、營(yíng)養(yǎng)不良等并發(fā)癥發(fā)生的因素之一。這對(duì)于抑制消化道腫瘤手術(shù)后患者高炎性反應(yīng)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(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735

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