谷氨酰胺对缺血-再灌注损伤大鼠肠黏膜炎性反应和通透性的影响
곡안선알대결혈-재관주손상대서장점막염성반응화통투성적영향
Effect of glutamine on the intestinal mucosa inflammatory reaction and permeability after ischemia-reperfusion in rats
  • 万方数据
    中华临床营养杂志 중화림상영양잡지
    CHINESE JOURNAL OF CLINICAL NUTRITION
    2013年 5期 292-299 ,共8页

    舒晓亮%钟静霞%康凯%柳先丽%徐涵

    서효량%종정하%강개%류선려%서함

    谷氨酰胺%缺血-再灌注损伤%肠黏膜%炎性反应%通透性 穀氨酰胺%缺血-再灌註損傷%腸黏膜%炎性反應%通透性
    곡안선알%결혈-재관주손상%장점막%염성반응%통투성
    Glutamine%Ischemia-reperfusion injury%Intestinal mucosa%Inflammatory reaction%Permeability
    目的 研究谷氨酰胺(Gln)对缺血-再灌注损伤大鼠肠黏膜炎性反应和通透性的影响.方法 将48只SD大鼠肠系膜上动脉夹闭造成缺血后恢复血流,建立肠缺血-再灌注损伤模型,将造模后的SD大鼠按随机数字表分为对照组(n=24)和模型+Gln组(n=24),两组大鼠肠内营养供给量为热量125.4 kJ/ (kg·d),氮量0.2g/ (kg·d),模型+Gln组喂饲肠内营养加3％ Gln,对照组大鼠喂饲肠内营养加3％大豆蛋白,造模后实验持续8d.检测造模前、造模后、实验第3天和第8天大鼠肠黏膜和血浆核因子-κB (NF-κB)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、Gln、D-乳酸(D-LAC)和二胺氧化酶(DAO)的变化.观察小肠黏膜形态学变化.结果 造模后对照组和模型+ Gln组大鼠肠黏膜NF-κB表达明显高于造模前(75.0％比0.0％,P=0.013; 70.8％比0.0％,P=0.019)；肠黏膜IL-6明显高于造模前[(313.27±75.28) pg/g比(227.52 ±58.13) pg/g,P=0.023; (321.75±74.46) pg/g比(227.52±58.13) pg/g,P=0.043];肠黏膜TNF-α[(241.28±65.29) pg/g、(240.35 ±64.86) pg/g]明显高于造模前[(172.45±33.76) pg/g,P=0.036,P=0.011];血浆IL-6[(150.32±18.74) ng/L、(148.21 ±20.19) ng/L]明显高于造模前[(116.37±14.59) ng/L,P=0.032,P=0.025];血浆TNF-α[(127.62±14.24) ng/L、(123.86±13.75) ng/L]明显高于造模前[(85.18±8.84) ng/L,P=0.018,P=0.035]; D-LAC[(0.46±0.03) mmol/L、(0.51 ±0.04) mmol/L]明显高于造模前[(0.27±0.02) mmol/L,P=0.041,P=0.018]; DAO[(2.76±0.57) U/ml、(2.58±0.51) U/ml]明显高于造模前[(1.52±0.24) U/ml,P=0.015,P =0.037]；而血浆Gln[(0.18±0.01) g/L、(0.21±0.01) g/L]明显低于造模前[(0.39±0.03) g/L,P =0.026,P=0.031].实验第3天和实验第8天,对照组大鼠肠黏膜NF-κB[16例(66.7％)、15例(62.5％)]显著高于造模前[0例(0.0％),P=0.027,P=0.002]；肠黏膜TNF-α[(226.23±55.35) pg/g、(214.76 ±54.82) pg/g]显著高于造模前[(172.45±33.76) pg/g,P=0.042,P=0.038];肠黏膜IL-6[(297.56±71.39) pg/g、(291.49±68.46) pg/g]显著高于造模前[(227.52±58.13) pg/g,P=0.031,P=0.012];血浆IL-6 [(147.38±17.25) ng/L、(144.65±15.32) ng/L]显著高于造模前[(116.37±14.59) ng/L,P=0.016,P=0.034];血浆TNF-α[(121.75±13.72)ng/L、(113.83±11.69) ng/L]显著高于造模前[(85.18±8.84) ng/L,P=0.025,P=0.041];D-LAC[(0.41 ±0.03) mmol/L、(0.53±0.05) mmol/L]显著高于造模前[(0.27±0.02) mmol/L,P=0.029,P=0.030]; DAO [(2.51±0.52) U/ml、(1.76±0.34) U/ml]显著高于造模前[(1.52±0.24) U/ml,P=0.034,P=0.016];但血浆Gln[(0.22±0.01) g/L、(0.21±0.03) g/L]显著低于造模前[(0.39±0.03) g/L,P=0.042,P=0.035].实验第3天模型+Gln组肠黏膜NF-κB、TNF-α、IL-6 [14例(58.3％)、(213.78±43.76) pg/g、(293.72±69.86) pg/g]明显高于造模前(P=0.038、0.026、0.013);血浆IL-6、TNF-α、D-LAC、DAO [(135.61 ±14.25) ng/L、(117.35±11.29)ng/L、(0.45 ±0.03) mmol/L、(2.26 ±0.43) U/ml]明显高于造模前(P=0.021、0.032、0.032、0.025).实验第8天模型+ Gln组肠黏膜NF-κB、TNF-α、IL-6[9例(37.5％)、(184.53 ±42.16) pg/g、(236.83 ±66.52) pg/g]明显低于造模后和对照组(P=0.024,P=0.027; P=0.026,P=0.039;P =0.013,P=0.028)；血浆IL-6、TNF-α、D-LAC、DAO[(126.35 ±12.74)ng/L、(92.76±9.42)ng/L、(0.31 ±0.02) mmol/L、(1.76 ±0.34) U/ml]明显低于造模后和对照组(P=0.021,P=0.030；P=0.032,P=0.025;P=0.024,P=0.037；P=0.022,P=0.036),而血浆Gln水平[(0.40±0.03) g/L]明显高于造模后和对照组(P =0.028、0.032).电镜下可见造模后绒毛、隐窝结构一定程度损害,绒毛稀疏且变短,固有膜内大量炎性细胞浸润,淋巴管扩张、水肿.实验第8天,模型+Gln组与造模后和对照组比较小肠绒毛、隐窝结构显著恢复；对照组与造模后比较肠黏膜绒毛、隐窝结构恢复不明显,固有膜内仍有炎性细胞浸润.结论 Gln通过调节肠黏膜炎性因子的释放,抑制炎症反应,降低肠黏膜的通透性,修复缺血-再灌注后损伤的肠黏膜.
    목적 연구곡안선알(Gln)대결혈-재관주손상대서장점막염성반응화통투성적영향.방법 장48지SD대서장계막상동맥협폐조성결혈후회복혈류,건립장결혈-재관주손상모형,장조모후적SD대서안수궤수자표분위대조조(n=24)화모형+Gln조(n=24),량조대서장내영양공급량위열량125.4 kJ/ (kg·d),담량0.2g/ (kg·d),모형+Gln조위사장내영양가3％ Gln,대조조대서위사장내영양가3％대두단백,조모후실험지속8d.검측조모전、조모후、실험제3천화제8천대서장점막화혈장핵인자-κB (NF-κB)、종류배사인자-α(TNF-α)、백세포개소-6(IL-6)、Gln、D-유산(D-LAC)화이알양화매(DAO)적변화.관찰소장점막형태학변화.결과 조모후대조조화모형+ Gln조대서장점막NF-κB표체명현고우조모전(75.0％비0.0％,P=0.013; 70.8％비0.0％,P=0.019)；장점막IL-6명현고우조모전[(313.27±75.28) pg/g비(227.52 ±58.13) pg/g,P=0.023; (321.75±74.46) pg/g비(227.52±58.13) pg/g,P=0.043];장점막TNF-α[(241.28±65.29) pg/g、(240.35 ±64.86) pg/g]명현고우조모전[(172.45±33.76) pg/g,P=0.036,P=0.011];혈장IL-6[(150.32±18.74) ng/L、(148.21 ±20.19) ng/L]명현고우조모전[(116.37±14.59) ng/L,P=0.032,P=0.025];혈장TNF-α[(127.62±14.24) ng/L、(123.86±13.75) ng/L]명현고우조모전[(85.18±8.84) ng/L,P=0.018,P=0.035]; D-LAC[(0.46±0.03) mmol/L、(0.51 ±0.04) mmol/L]명현고우조모전[(0.27±0.02) mmol/L,P=0.041,P=0.018]; DAO[(2.76±0.57) U/ml、(2.58±0.51) U/ml]명현고우조모전[(1.52±0.24) U/ml,P=0.015,P =0.037]；이혈장Gln[(0.18±0.01) g/L、(0.21±0.01) g/L]명현저우조모전[(0.39±0.03) g/L,P =0.026,P=0.031].실험제3천화실험제8천,대조조대서장점막NF-κB[16례(66.7％)、15례(62.5％)]현저고우조모전[0례(0.0％),P=0.027,P=0.002]；장점막TNF-α[(226.23±55.35) pg/g、(214.76 ±54.82) pg/g]현저고우조모전[(172.45±33.76) pg/g,P=0.042,P=0.038];장점막IL-6[(297.56±71.39) pg/g、(291.49±68.46) pg/g]현저고우조모전[(227.52±58.13) pg/g,P=0.031,P=0.012];혈장IL-6 [(147.38±17.25) ng/L、(144.65±15.32) ng/L]현저고우조모전[(116.37±14.59) ng/L,P=0.016,P=0.034];혈장TNF-α[(121.75±13.72)ng/L、(113.83±11.69) ng/L]현저고우조모전[(85.18±8.84) ng/L,P=0.025,P=0.041];D-LAC[(0.41 ±0.03) mmol/L、(0.53±0.05) mmol/L]현저고우조모전[(0.27±0.02) mmol/L,P=0.029,P=0.030]; DAO [(2.51±0.52) U/ml、(1.76±0.34) U/ml]현저고우조모전[(1.52±0.24) U/ml,P=0.034,P=0.016];단혈장Gln[(0.22±0.01) g/L、(0.21±0.03) g/L]현저저우조모전[(0.39±0.03) g/L,P=0.042,P=0.035].실험제3천모형+Gln조장점막NF-κB、TNF-α、IL-6 [14례(58.3％)、(213.78±43.76) pg/g、(293.72±69.86) pg/g]명현고우조모전(P=0.038、0.026、0.013);혈장IL-6、TNF-α、D-LAC、DAO [(135.61 ±14.25) ng/L、(117.35±11.29)ng/L、(0.45 ±0.03) mmol/L、(2.26 ±0.43) U/ml]명현고우조모전(P=0.021、0.032、0.032、0.025).실험제8천모형+ Gln조장점막NF-κB、TNF-α、IL-6[9례(37.5％)、(184.53 ±42.16) pg/g、(236.83 ±66.52) pg/g]명현저우조모후화대조조(P=0.024,P=0.027; P=0.026,P=0.039;P =0.013,P=0.028)；혈장IL-6、TNF-α、D-LAC、DAO[(126.35 ±12.74)ng/L、(92.76±9.42)ng/L、(0.31 ±0.02) mmol/L、(1.76 ±0.34) U/ml]명현저우조모후화대조조(P=0.021,P=0.030；P=0.032,P=0.025;P=0.024,P=0.037；P=0.022,P=0.036),이혈장Gln수평[(0.40±0.03) g/L]명현고우조모후화대조조(P =0.028、0.032).전경하가견조모후융모、은와결구일정정도손해,융모희소차변단,고유막내대량염성세포침윤,림파관확장、수종.실험제8천,모형+Gln조여조모후화대조조비교소장융모、은와결구현저회복；대조조여조모후비교장점막융모、은와결구회복불명현,고유막내잉유염성세포침윤.결론 Gln통과조절장점막염성인자적석방,억제염증반응,강저장점막적통투성,수복결혈-재관주후손상적장점막.
    Objective To study the effect of glutamine (Gln) on the intestinal mucosa inflammatory reaction and permeability after intestine ischemia-reperfusion injury in rats.Methods The rat model of intestinal ischemia-reperfusion injury was established by clamping the mesenteric superior artery and then restoring blood flow.Forty-eight model rats were divided into control group (n =24) and model + Gln group (n =24)according to the stochastic indicator method.Both groups were given enteral nutrition with equal energy and nitrogen [energy 125.4 kJ/ (kg · d) and nitrogen 0.2 g/ (kg · d)].The model +Gln group was fed with enteral nutrition plus 3％ Gln,while the control group was fed with enteral nutrition plus 3％ soybean protein.The experiment lasted 8 days after modeling.The intestinal mucosa and the plasma levels of nuclear factor-κB (NF-κB),tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),Gln,D-LACtic acid and diamine oxidase (DAO) were observed in rats before and after modeling and on the 3rb and 8rd day of the experiment.Changes in the morphology of intestinal mucosa were observed by electron microscopy.Results After modeling in control and model + Gln group,the level of NF-κB in intestinal mucosa [18 cases (75.0％) and 17 cases (70.8％)] were significantly higher than those before modeling [0 case (0.0％),P =0.013,P =0.019],the level of IL-6 in intestinal mucosa [(313.27±75.28) pg/g and (321.75±76.46) pg/g] were significantly higher than those before modeling [(227.52 ±58.13) pg/g,P =0.023,P =0.043],and the level of TNF-α in intestinal mucosa [(241.28 ±65.29) pg/g and (240.35 ±64.86) pg/g] were significantly higher than those before modeling [(172.45 ±33.76) pg/g,P=0.036,P=0.011].The plasma level of IL-6 [(150.32 ± 18.74) ng/L and (148.21 ±20.19) ng/L] were significantly higher than those before modeling [(116.37 ± 14.59) ng/L,P =0.032,P =0.025],the plasma level of TNF-α [(127.62 ± 14.24) ng/Land (123.86 ± 13.75) ng/L] were significantly higher than those before modeling [(85.18 ± 8.84) ng/L,P =0.018,P =0.035],and the plasma level of D-LAC [(0.46 ±0.03) mmol/L and (0.51 ±0.04) mmol/L]were significantly higher than those before modeling [(0.27 ±0.02) mmol/L,P =0.041,P =0.018],and the plasma level ofDAO [(2.76±0.57) U/ml and (2.58 ±0.51) U/ml] were significantly higher than those before modeling [(1.52±0.24) U/ml,P=0.015,P=0.037],while the plasma level of Gln [(0.18 ±0.01) g/L and (0.21 ± 0.01) g/L] were significantly lower than those before modeling [(0.39 ± 0.03) g/L,P =0.026,P =0.031].On the 3rd and 8th days of the experiment in the control group,the level of NF-κB in intestinal mucosa [16 cases (66.7％),15 cases (62.5％)] were significantly higher than those before modeling (P =0.027,P =0.002),the level of TNF-α in intestinal mucosa [(226.23 ±55.35) pg/g and (214.76 ±54.82) pg/g] were significantly higher than those before modeling (P=0.042,P =0.038)],the level of IL-6in intestinal mucosa [(297.56 ± 71.39) pg/g and (291.49 ± 68.46) pg/g] were significantly higher than those before modeling (P =0.031,P =0.012).On the 3rd and 8th days in the control group,the plasma level of IL-6[(147.38 ± 17.25) ng/L and (144.65 ± 15.32) ng/L] were significantly higher than those before modeling (P =0.016,P =0.034),the plasma level of TNF-α [(121.75 ± 13.72) ng/L and (113.83 ± 11.69) ng/L] were significantly higher than those before modeling (P =0.025,P =0.041),the plasma level of D-LAC [(0.41 ±0.03) mmol/L and (0.53 ±0.05) mmol/L)] were significantly higher than those before modeling (P =0.029,P =0.030),the plasma level of DAO [(2.51 ± 0.52) U/ml and (1.76 ± 0.34) U/ml] were significantly higher than those before modeling (P =0.034,P =0.016).The plasma level of Gln [(0.22 ±0.01) g/L and (0.21 ±0.03) g/L] were significantly lower than those before modeling (P =0.042,P =0.035).On the 3rd day of the experiment in the model + Gln group,the levels of NF-κB,TNF-α,and IL-6 in intestinal mucosa [14 cases (58.3％),(213.78 ±43.76) pg/g,(293.72 ±69.86) pg/g] were significantly higher than those before modeling (P =0.038,P =0.026,P =0.013) ; the plasma level of IL-6,TNF-α,D-LAC,and DAO [(135.61 ±14.25) ng/L,(117.35 ±11.29) ng/L,(0.45 ±0.03) mmol/L,and (2.26 ± 0.43) U/ml] were significantly higher than those before modeling (P =0.021,P =0.032,P =0.032,P =0.025).On the 8th day of the experiment in the model + Gln group,the levels of NF-κB,TNF-α,and IL-6 in intestinal mucosa [9 cases (37.5％),(184.53 ± 42.16) pg/g,and (236.83 ±66.52) pg/g] were significantly lower than those after modeling and those in the control group (P =0.024,P=0.027; P=0.026,P=0.039; P=0.013,P=0.028) ; the plasma levels of IL-6,TNF-α,D-LAC,and DAO [(126.35±12.74) ng/L,(92.76±9.42) ng/L,(0.31 ±0.02) mmol/L,and (1.76±0.34) U/ml]were significantly lower than those after modeling and those in the control group (P =0.021,P =0.030; P =0.032,P =0.025 ; P =0.024,P =0.037 ; P =0.022,P =0.036) ; the plasma level of Gln [(0.40 ±0.03) g/L] was significantly higher than those after modeling and in the control group (P =0.028,P =0.032).Under the electron microscope,the structure of villus and recess was damaged after modeling,villi were sparse and short,with a lot of inflammatory cell infiltration in the lamina propria.Lymphangiectasia and edema occured after modeling.On the 8th day,compared with after modeling and the control group,intestinal villi and recess structure were significantly restored in the model + Gln group; compared with the after-modeling status,the recovery of intestinal mucosa villi and recess structure was not obvious,and the inflammatory cell infiltration in the lamina propria persisted in the control group.Conclusion Gln repairs ischemia-reperfusion injury in the intestinal mucosa by regulating intestinal mucosa inflammatory cytokine release,inhibitng inflammatory response,and reducing the permeability of the intestinal mucosa.
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