張紅波

(內(nèi)蒙古醫(yī)科大學(xué)第一附屬醫(yī)院 胃腸外科，內(nèi)蒙古 呼和浩特 010050)

臨床醫(yī)學(xué)研究

含橄欖油脂肪乳對(duì)消化道手術(shù)術(shù)后炎性因子與機(jī)體免疫的影響

張紅波

(內(nèi)蒙古醫(yī)科大學(xué)第一附屬醫(yī)院 胃腸外科，內(nèi)蒙古 呼和浩特 010050)

目的 比較含橄欖油脂肪乳與中長(zhǎng)鏈脂肪乳對(duì)消化道手術(shù)患者術(shù)后炎性因子與機(jī)體免疫功能的影響。方法 將2014年1月至2015年12月入選的95例消化道手術(shù)患者隨機(jī)分為研究組(49例)、對(duì)照組(46例)，兩組術(shù)后均給予腸外營(yíng)養(yǎng)支持，研究組輸注含橄欖油脂肪乳(20%克林諾)，對(duì)照組輸注中長(zhǎng)鏈脂肪乳(20%力保肪寧)，比較兩組患者術(shù)前及術(shù)后1、3、5 d炎性介質(zhì)、機(jī)體免疫、肝腎功能等生化指標(biāo)。結(jié)果 兩組患者術(shù)后各觀察時(shí)點(diǎn)TP、ALT、Cr、FBG差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。研究組術(shù)后3、5 d TNF-α[3 d (64.9±17.8 vs.72.4±18.6) pg/mL;5 d(55.6±16.5 vs.67.4±17.4) pg/mL]、CRP[3 d(31.8±6.8 vs.35.8±7.2) mg/L;5 d(27.5±6.2 vs.31.3±7.8) mg/L]、IL-6[3 d(55.5±9.8vs.60.6±11.5) pg/m;5 d(50.8±9.1 vs.55.7±10.3) pg/m]均顯著低于對(duì)照組 (P<0.05)。兩組患者術(shù)后各觀察時(shí)點(diǎn)IgA、IgG、IgM、CD3+%差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，研究組術(shù)后5 d CD 4+/CD 8+(1.61±0.33 vs.1.47±0.32)顯著高于對(duì)照組(P<0.05) 。結(jié)論 含橄欖油脂肪乳較中長(zhǎng)鏈脂肪乳更能明顯降低消化道手術(shù)患者術(shù)后應(yīng)激反應(yīng)水平，具有改善細(xì)胞免疫的潛在優(yōu)勢(shì)。

脂肪乳；橄欖油；消化道手術(shù)；炎性介質(zhì)；免疫功能

消化道手術(shù)患者術(shù)后常通過(guò)腸外營(yíng)養(yǎng)支持(parenteral nutrition,PN)獲取機(jī)體所需能量，圍術(shù)期靜脈輸注脂肪乳制劑會(huì)對(duì)機(jī)體免疫功能與炎性介質(zhì)的表達(dá)產(chǎn)生重要影響，近年來(lái)，一種由橄欖油和大豆油按4 ∶1比例混合而成的脂肪乳逐步應(yīng)用于臨床，與臨床應(yīng)用較為廣泛的中長(zhǎng)鏈脂肪乳(medium and long chain triglycerides,MCT/LCT)相比，含橄欖油脂肪乳劑能夠促進(jìn)術(shù)后血漿蛋白的恢復(fù)，有益于縮短術(shù)后住院時(shí)間，對(duì)細(xì)胞免疫功能與肝腎功能的影響較小，但亦有研究表明二者對(duì)胃腸患者肝腎功能、免疫功能及炎癥應(yīng)答的影響相似。筆者通過(guò)隨機(jī)對(duì)照研究，將二者對(duì)消化道手術(shù)患者術(shù)后炎性因子與機(jī)體免疫的影響進(jìn)行了探討，結(jié)果如下。

1 資料與方法

1.1 病例納入與排除標(biāo)準(zhǔn) 入組標(biāo)準(zhǔn)：18歲<年齡<60歲，需要PN支持>5 d的消化道手術(shù)患者，患者本人或家屬均知情同意。排除標(biāo)準(zhǔn)：術(shù)前心肝腎功能及甲狀腺、腎上腺功能異常者，糖尿病患者，近期使用免疫調(diào)節(jié)劑者或自身免疫性疾病患者，術(shù)前輔助放化療者，術(shù)前合并嚴(yán)重感染患者，哺乳期婦女。

1.2 臨床資料與分組 研究獲得本院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn)，入選2014年1月至2015年12月間收治的95例消化道手術(shù)患者為研究對(duì)象?；颊呷虢M后根據(jù)隨機(jī)數(shù)字表分為研究組(49例)、對(duì)照組(46例)，分別予不同術(shù)后營(yíng)養(yǎng)支持方案，兩組患者基礎(chǔ)臨床特征經(jīng)比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05，見表1)。

表1 兩組患者臨床特征比較 [n(%)]

臨床特征研究組(49例)對(duì)照組(46例)χ2P性別男28(57.1)22(47.8)女21(42.9)24(52.2)0.8260.363年齡(歲)30～11(22.4)7(15.2)40～20(40.8)22(47.8)50～18(36.7)17(37.0)0.9190.632手術(shù)名稱食管癌根治術(shù)9(18.4)13(28.3)胃大部切除術(shù)22(44.9)18(39.1)小腸腫瘤切除術(shù)5(10.2)6(13.0)大腸癌根治術(shù)13(26.5)9(19.6)1.8530.604手術(shù)方式腹腔鏡手術(shù)30(61.2)24(52.2)非腹腔鏡手術(shù)19(38.8)22(47.8)0.7920.373BMI(kg/m2)<2534(69.4)30(65.2)≥2515(30.6)16(34.8)0.1880.665

1.3 腸外營(yíng)養(yǎng)支持方案 兩組患者術(shù)后均通過(guò)經(jīng)外周靜脈穿刺中心靜脈置管術(shù)(peripherally inserted central catheter)實(shí)施PN支持。研究組選用含橄欖油脂肪乳劑(克林諾,250 mL/瓶,上海百特醫(yī)療用品有限公司,國(guó)藥準(zhǔn)字H20070193)聯(lián)合氨基酸葡萄糖溶液聯(lián)合靜脈滴注,對(duì)照組選用中長(zhǎng)鏈脂肪乳劑(medium and long chain triglycerides,MCT/LCT) (力保肪寧,250 mL/瓶，德國(guó)貝朗醫(yī)療有限公司,國(guó)藥準(zhǔn)字J20090064)聯(lián)合氨基酸葡萄糖溶液靜脈滴注，連續(xù)5 d。兩組術(shù)后均按照等總熱量104.6 kJ/(kg·d)、等氮量0.2 g/(kg·d)予PN支持，術(shù)后第1天，脂肪和葡萄糖用量減半，術(shù)后2～5 d予全營(yíng)養(yǎng)支持，同時(shí)按每公斤體重補(bǔ)充足量電解質(zhì)、維生素、微量元素。

1.4 觀察指標(biāo) 術(shù)前1 d與術(shù)后1、3、5 d采血檢測(cè)血清總蛋白(TP)、血清丙氨酸轉(zhuǎn)氨酶(ALT)、肌酐(Scr)、空腹血糖(FBG) 、炎性介質(zhì)[腫瘤壞死因子(TNF-α)、C反應(yīng)蛋白(CRP)、白介素-6(IL-6)]、免疫球蛋白(IgA、IgG、IgM)、T細(xì)胞亞群(CD 3+、CD 4+/CD 8+)水平，比較兩組不同觀察時(shí)點(diǎn)上述指標(biāo)差異。

1.5 統(tǒng)計(jì)學(xué)方法 采用SPSS 19.0軟件建數(shù)據(jù)庫(kù)并進(jìn)行分析，組間生化指標(biāo)、免疫指標(biāo)、炎性介質(zhì)指標(biāo)的比較t檢驗(yàn)，組內(nèi)不同時(shí)點(diǎn)多組平均數(shù)比較采用重復(fù)測(cè)量方差分析，臨床特征構(gòu)成比較采用χ2檢驗(yàn)，P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 血液生化指標(biāo)比較 兩組患者術(shù)后ALT、Cr、FBG較術(shù)前呈現(xiàn)先上升后下降趨勢(shì)，TP呈現(xiàn)先下降后上升趨勢(shì)；組間上述指標(biāo)在術(shù)后各觀察時(shí)點(diǎn)差異均無(wú)統(tǒng)計(jì)學(xué)意義(P<0.05，見表2)。

指標(biāo)組別例數(shù)術(shù)前1d術(shù)后1d術(shù)后3d術(shù)后5dFPTP(g/L)研究4968.9±7.560.3±6.565.5±7.869.4±7.915.154<0.001對(duì)照4670.6±8.160.9±7.064.7±7.468.5±7.517.322<0.001t1.0620.4330.5120.560P0.2910.6660.6100.577ALT(U/L)研究4920.4±6.830.5±8.226.7±6.325.5±6.28.564<0.001對(duì)照4622.0±6.132.9±7.826.2±5.725.1±6.310.483<0.001t1.2041.4600.4050.312P0.2320.1480.6860.756Cr(μmol/L)研究4979.9±17.390.8±23.185.2±18.581.8±17.312.617<0.001對(duì)照4677.6±14.787.5±18.483.6±17.679.4±17.010.231<0.001t0.6960.7670.4310.681P0.4880.4450.6670.498FBG(mmol/L)研究495.3±1.56.8±1.16.5±1.36.2±1.27.592<0.001對(duì)照465.1±1.56.5±1.46.4±1.16.1±1.06.753<0.001t0.6491.1650.4030.440P0.5180.2470.6880.661

2.2 炎性因子水平比較 兩組患者術(shù)后TNF-α、CRP、IL-6較術(shù)前均呈現(xiàn)先上升后下降趨勢(shì)；研究組術(shù)后3、5 d上述指標(biāo)均顯著低于對(duì)照組水平(P<0.05，見表3)。

指標(biāo)組別例數(shù)術(shù)前1d術(shù)后1d術(shù)后3d術(shù)后5dFPTNF-α(pg/mL)研究4950.4±18.178.3±24.364.9±17.855.6±16.511.625<0.001對(duì)照4648.6±15.781.5±22.672.4±18.667.4±17.414.403<0.001t0.5160.6632.0142.126P0.6070.5090.0470.033CRP(mg/L)研究4910.1±3.342.6±8.531.8±6.827.5±6.213.862<0.001對(duì)照469.2±3.540.5±9.935.8±7.231.3±7.816.527<0.001t1.3881.1112.7842.637P0.1680.2690.0070.010IL-6(pg/mL)研究4941.6±11.565.7±13.555.5±9.850.8±9.19.824<0.001對(duì)照4638.8±10.167.3±11.960.6±11.555.7±10.313.365<0.001t1.2580.6202.3312.461P0.2120.5370.0220.016

2.3 免疫水平比較 兩組患者術(shù)后IgA、IgG、IgM、CD 3+%、CD 4+/CD 8+均較術(shù)前呈先下降后上升趨勢(shì)；兩組術(shù)后各觀察時(shí)點(diǎn)IgA、IgG、IgM、CD 3+%差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，研究組術(shù)后5 d CD 4+/CD 8+顯著高于對(duì)照組(P<0.05，見表4)。

指標(biāo)組別例數(shù)術(shù)前1d術(shù)后1d術(shù)后3d術(shù)后5dFPIgA(g/L)研究492.31±0.682.16±0.652.28±0.722.35±0.772.2270.084對(duì)照462.27±0.752.11±0.792.23±0.752.30±0.742.0130.112t0.2730.2120.2080.202P0.7850.8330.8360.840IgG(g/L)研究4913.04±2.8112.31±2.1712.75±2.3113.18±2.951.7190.163對(duì)照4612.96±2.5312.57±2.3512.82±2.3913.09±2.782.0750.103t0.1460.5610.0910.096P0.8840.5760.9280.924IgM(g/L)研究491.35±0.431.07±0.331.12±0.431.36±0.581.7460.157對(duì)照461.41±0.551.11±0.501.14±0.471.28±0.651.9750.405t0.2970.4630.2390.634P0.7670.6440.8120.528CD3+(%)研究4955.9±9.152.4±9.355.8±9.959.0±9.62.4500.063對(duì)照4655.2±10.551.2±10.955.1±9.556.3±9.11.9820.116t0.3480.5780.3511.405P0.7290.5650.7260.163CD4+/CD8+研究491.22±0.391.14±0.371.42±0.351.61±0.332.7540.042對(duì)照461.24±0.361.11±0.421.37±0.371.47±0.322.2470.083t0.2590.3700.6772.097P0.7960.7120.5000.039

3 討論

脂肪乳劑是將油脂、乳化劑、等滲劑等與水經(jīng)過(guò)特殊工藝技術(shù)混合制成的乳化液體，除提供機(jī)體代謝所需熱量外，尚能提供人體不能合成亞油酸、亞麻酸和二十碳四烯酸等不飽和脂肪酸。力保肪寧是新型脂肪乳劑，是在LCT基礎(chǔ)上加入50%MCT混合而成，較傳統(tǒng)LCT在脂肪代謝、節(jié)氮作用及對(duì)免疫功能的影響等方面具備明顯優(yōu)勢(shì)，且具有良好的肝臟耐受性，是目前臨床應(yīng)用最為廣泛的脂肪乳劑?？肆种Z是由80%橄欖油和20%大豆油混合構(gòu)成脂肪乳劑，含有15%飽和脂肪酸(SFA)、65%ω-9單不飽和脂肪酸(MUFA)和20%多不飽和脂肪酸(PUFA)。其中，橄欖油是從橄欖果仁中提取的植物油，主要成分是油酸，屬于ω-9 MUFA，與ω-6 PUFA相比，由于其碳鏈上含有較少雙鍵而不易發(fā)生氧化反應(yīng)，因此克林諾較力保肪寧降低了脂肪乳劑中ω-6脂肪酸的含量及促炎性衍生物的產(chǎn)生，輸入體內(nèi)可間接發(fā)揮抗炎作用；且橄欖油富含α-生育酚、鯊烯、植物甾醇等成分，α-生育酚是天然的維生素E異構(gòu)體，能降低脂質(zhì)過(guò)氧化損傷和致炎因子生成，減輕了對(duì)T細(xì)胞應(yīng)答的損害，有助于維護(hù)機(jī)體免疫功能。

大型手術(shù)后免疫炎癥反應(yīng)失衡是患者發(fā)生多器官功能障礙甚至死亡的重要原因。本研究中，兩組患者術(shù)后炎性因子水平雖呈相似變化趨勢(shì)，但研究組術(shù)后3 d和5 d的TNF-α、CRP和IL-6水平均顯著低于對(duì)照組，說(shuō)明研究組術(shù)后炎性應(yīng)激程度低于對(duì)照組，根據(jù)上述脂肪乳成分分析，可以推測(cè)克林諾較力保肪寧能抑制術(shù)后炎性因子的過(guò)度表達(dá)，減輕術(shù)后炎性應(yīng)激。相關(guān)報(bào)道，ω-9MUFA能減輕危重癥病人的氧化應(yīng)激和過(guò)度炎癥反應(yīng)；重癥患兒輸注含橄欖油脂肪乳后脂質(zhì)過(guò)氧化發(fā)生概率要低于應(yīng)用大豆油脂肪乳患兒。免疫功能評(píng)價(jià)，術(shù)后5 d研究組CD 3+%、CD 4+/CD 8+比值均高于對(duì)照組，后者組間差異更有統(tǒng)計(jì)學(xué)意義，亦進(jìn)一步說(shuō)明克林諾中橄欖油的抗氧化功能較力保肪寧能減輕對(duì)T細(xì)胞的過(guò)氧化損傷，改善術(shù)后免疫抑制。對(duì)ICU患者采用含橄欖油脂肪乳與MCT/LCT脂肪乳比較研究表明，前者治療7 d后血總淋巴細(xì)胞計(jì)數(shù)(2.66±0.22vs.2.01±0.26)×109、CD 4+/CD 8+(2.03±0.18 vs.1.25±0.12)顯著高于對(duì)照組，本研究結(jié)果與之相似。從營(yíng)養(yǎng)供給與代謝角度講，克林諾所包含的橄欖油和大豆油均屬長(zhǎng)鏈脂肪酸，在供能和節(jié)氮作用基本相同，故在術(shù)后TP、ALT、Scr、FBG方面，未表現(xiàn)出顯著性差異。

綜上所述，對(duì)消化道大型手術(shù)患者術(shù)后輸注含橄欖油的脂肪乳與常規(guī)MCT/LCT均具有良好效果，二者對(duì)肝腎功能、血糖的影響相近，前者能有效的減輕術(shù)后炎性應(yīng)激，對(duì)細(xì)胞免疫功能的影響更小，具有比較優(yōu)勢(shì)。

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[收稿2016-10-24;修回2017-01-10]

(編輯：王福軍)

Effects of fat emulsion containing olive oil on postoperative inflammatory factors and immune function in patients with digestive tract surgery

ZhangHongbo

(Department of Gastrointestinal Surgery,First Affiliated Hospital of Inner Mongolia Medical University,Hohhot，Inner Mongolia 010050,China)

Objective To compare the effects between fatty emulsion containing olive oil and medium and long chain triglycerides (MCT/LCT) on postoperative inflammatory factors and immune function in patients with digestive tract surgery.Methods A total of 95 gastrointestinal surgery patients from January，2014 to December，2015 were selected as study objects，and were divided into study group (49 cases) and control group (46 cases) according to the random number table.Two groups were given parenteral nutrition (PN) support，while the study group was given fat emulsion containing olive oil (20% Clin) and the control group was given MCT/LCT (20% Lipofundin).Inflammation mediators，immune function，liver and kidney function and other biochemical indicators before and after surgery were compared between the two groups.Results There were no significant differences of TP，ALT，Cr and FBG between the two groups at each observation time point (P>0.05).TNF-α [3 d (64.9±17.8 vs.72.4±18.6) pg/ml;5 d (55.6±16.5 vs.67.4±17.4) pg/ml]、CRP [3 d (31.8±6.8 vs.35.8±7.2) mg/L;5 d (27.5±6.2 vs.31.3±7.8) mg/L]、IL-6 [ 3 d (55.5±9.8 vs.60.6±11.5) pg/m;5 d (50.8±9.1 vs.55.7±10.3) pg/m] 3 d and 5 d after operation in the study group were significantly lower than those in the control group (P<0.05).The differences of the percentage of IgA，IgM，IgG and CD3+between the two groups after operation were not statistically significant (P>0.05)，whereas CD 4+/CD 8+in the study group 5 d after operation was significantly higher than that in the control group(1.61±0.33 vs.1.47±0.32) (P<0.05).Conclusion Compared with MCT/LCT，fat emulsion containing olive oil could significantly reduce stress response level in patients with digestive tract surgery，and has the potential of improving cellular immunity，and the effects on liver and renal function are similar.

fat emulsion; olive oil; digestive tract surgery; inflammatory mediators; immune function

R656

A

1000-2715(2017)02-0180-05