短肠大鼠结肠对^15N—甘氨酸的吸收研究

目的探讨短肠大鼠的结肠对氨基酸代偿吸收能力。方法切除80%小肠的短肠大鼠,经肠喂养21天后,测定结肠对     

短肠综合征时结肠的代偿研究

目的　观察及评价短肠大鼠结肠代偿性增生及结肠对营养物质吸收的促进作用。　方法　制作切除（80～85）%的超短肠大鼠模型,用百普素(Pepti-2000)做肠内营养（EN）治疗,观察全身营养状况和结肠形态学的改变,并在术后第21天用木糖和15N-甘氨酸混合液对带血管蒂的结肠进行封闭式灌注,观察结肠对水、碳水化合物和氨基酸的吸收情况。　结果　EN组于术后第21天净氮平衡与对照组（CONT）无差异,体重仅比术前减轻(10±18)g。结肠壁明显增厚,皱襞增大增粗,结肠壁的厚度、粘膜厚度、皱襞高度和皱襞表面积与CONT组相比差异具有非常显著性意义（P＜0.01）。EN组与CONT组相比DNA指数1.21±0.11vs.1.01±0.15(P＜0.05),S期细胞百分比（52.6±5.5）%vs.（42.9±4.1）%（P＜0.05）。连续循环灌注3h之后EN组对水、木糖和氨基酸的吸收明显高于CONT组（P＜0.05）。　结论　大鼠结肠在短肠综合征时发生了明显的形态和功能上的代偿。早期适当的肠内营养不但可使超短肠大鼠获得足够营养支持,并且能够促进短肠大鼠结肠代偿。     

谷氨酰胺对短肠综合征大鼠模型结肠黏膜作用的初步研究

目的 探讨谷氨酰胺联合肠内营养对动物模型结肠黏膜的影响。方法 将大鼠随机分为5组，即模型肠内营养组、谷氨酰胺大剂量＋肠内营养组，谷氨酰胺中剂量＋肠内营养组，谷氨酰胺小剂量＋肠内营养组。分为7天，14天2个时间点进行观察。结果 Gln各组肠壁肌层增厚明显，皱襞明显增高，肠腺数量增多，其中大、中剂量组的皱襞不仅高且密集，皱襞高度、肠腺密度均明显大于模型组（P〈0．01）。结论 谷氨酰胺＋肠内营养比单用营养的模型组更可以促进大鼠结肠的代偿，大、中剂量组优于小剂量组。     

重组生长激素促短肠大鼠结肠代偿机制的探讨

目的　探讨重组生长激素促短肠大鼠结肠代偿的作用机制。方法　将短肠大鼠分成肠内营养（EN）和肠内营养+重组生长激素（EG）两组。结果　自术后第15天起,EG组体重的减轻明显低于EN组(P＜0.05),术后第21天起体重已大于术前;EG组氮平衡的改善明显好于EN组;血浆蛋白水平也高于EN组(P＜0.05);EG组结肠壁胰岛素样生长因子1(IGF-1)mRNA含量比EN组明显升高〔(1291±43）vs.（1026±42）,P＜0.05〕,IGF-1受体mRNA含量明显降低〔(899±5）vs.（1113±7）,P＜0.05〕;EG组的血IGF-1水平明显高于EN组〔(455±107）ng/mlvs．（329±68）ng/ml,P＜0.05〕,GH水平也显著升高〔(9.7±3.3）ng/mlvs.（5.8±2.4）ng/ml,P＜0.05〕。结论　重组生长激素可促使短肠大鼠IGF-1和结肠壁IGF-1mRNA的合成及残留肠道对营养物质吸收。     

谷氨酰胺对短肠综合征大鼠结肠黏膜细胞凋亡的影响

目的 探讨谷氨酰胺联合肠内营养对动物模型结肠黏膜凋亡的影响。方法 将大鼠随机分为3组，即正常组，模型组、谷氨酰胺组2l天两个时间点进行观察。结果 谷氨酰胺组BCl-2的平均灰度值及表达阳性的面积明显大于其他组，Bax基因蛋白平均灰度值及表达阳性的面积明显小于其他组（P〈0．05）。结论 谷氨酰胺能抑制结肠黏膜细胞的凋亡，促进结肠的代偿。     

肠内营养促短肠大鼠结肠代偿性增生

观察及评价肠内营养（ＥＮ）对治疗短肠大鼠的作用和短肠大鼠结肠形态学代偿性增生的作用。方法：制作切除８０％～８５％的超短肠大鼠模型,用Ｐｅｐｔｉ－２０００作ＥＮ治疗,观察其全身营养状况和结肠形态学的改变。结果：ＥＮ组存活率高达７６．９％,于术后第２１天净氮平衡与对照组无差异,体重仅比术前减轻１０ｇ±１．８ｇ。结肠壁明显增厚,皱襞增大增粗,结肠壁的厚度、粘膜厚度、腺上皮高度和表面积与对照组相比差异非常显著（Ｐ＜０．００１）。ＥＮ组与对照组相比：ＤＮＡ指数１．２１±０．１１比１．０１±０．１５（Ｐ＜０．０５）,Ｓ期细胞百分比５２．６％±５．５％比４２．９％±４．１％（Ｐ＜０．０５）。ＥＮ组的ＩＧＦ－１ｍＲＮＡ含量比对照组有极明显增高（１０２６±４２比７３８±４．４,Ｐ＜０．０１）。结论：大鼠结肠在短肠综合征时发生了明显的形态学代偿性增生。早期适当的肠内营养不但可使超短肠大鼠获得足够营养支持,并且能够促进结肠的形态学和功能上的代偿。     

结肠在短肠综合征中的代偿作用

短肠综合征 (ｓｈｏｒｔｂｏｗｅｌｓｙｎｄｒｏｍｅ,ＳＢＳ)是指小肠切除 70 %以上 ,引起水电解质及营养物质吸收减少的综合病征[1] 。ＳＢＳ常易导致水电解质平衡紊乱及严重的营养不良 ,尤其是对一些极短肠 (残留小肠 <30ｃｍ[2 ] )乃至全小肠切除的患者 ,若处理不当可使病情恶化甚至造成患者死亡。ＳＢＳ主要病因有 :肠系膜血管血栓形成或栓塞、肠扭转、外伤性肠系膜血管破裂、腹内疝和Ｃｒｏｈｎ病等。 70年代后期 ,随着肠外营养 (ＰＮ)的发展 ,患者通过肠外途径获得足够的营养支持 ,营养不良的状况得以明显改善[3 ] 。但较长时间的ＰＮ…     

生长激素对短肠大鼠残留小肠形态及生长代谢的影响

目的　探讨单纯肠外营养 (PN)与添加生长激素 (GH)的PN对短肠大鼠残留小肠代偿的作用及作用机制。方法　将 2 0只短肠SD大鼠随机分成PN组及PN rhGH组。行细胞增殖核抗原 (PCNA)测定、原位末端标记 (TUNEL)染色及bcl 2、BaxmRNA测定。结果　PN组残留小肠粘膜明显萎缩 ,PN rhGH组肠萎缩显著改善。PCNA表达在PN组降低 [(8.37± 2 .2 3)个 /视野 ],PN rhGH组增高 [(19.2 8± 3.2 5 )个 /视野 ],差异有非常显著性 (P <0 .0 1)。凋亡指数在PN组增高 [(2 2 .32± 3.84)个 / 10 0细胞 ],PN rhGH组降低 [(8.0 6± 2 .2 3)个 / 10 0细胞 ],差异有非常显著性(P <0 .0 1)。bcl 2mRNA表达在PN组降低 (0 .2 0± 0 .0 3) ,在PN rhGH组增高 (0 .44± 0 .0 6 ) ,BaxmRNA表达则相反。结论　单纯PN使短肠大鼠残留小肠粘膜明显萎缩 ,rhGH通过促进肠粘膜上皮细胞增生与抑制肠粘膜上皮细胞凋亡 ,显著促进残留小肠的代偿适应。     

结肠瓣膜成形术诱导SD大鼠短肠综合征模型结肠上皮化生的机制研究

目的 结肠瓣膜成形术可以使瓣膜前结肠上皮具有类似小肠的吸收功能,本研究拟进一步阐明结肠瓣膜成形术诱导结肠上皮向小肠上皮化生的机制。方法 将40只大鼠随机分配到两组（各20只）,对照组大鼠切除80%小肠,实验组同时行结肠瓣膜成形术。实验后30周处死大鼠,取回肠、瓣膜前结肠及瓣膜后结肠作检测。原位荧光免疫组化法检测肠上皮细胞内Wnt7b蛋白和β-catenin蛋白。结果 实验组大鼠比对照组的大鼠重。HE染色光镜检查发现瓣膜近端的结肠具有类似小肠上皮的特征（上皮增厚、肠隐窝增长以及杯状细胞减少）。免疫组化检查发现瓣膜近端结肠上皮的Wnt7b蛋白和β-catenin蛋白比瓣膜远端结肠上皮的大幅增多。结论 结肠瓣膜成形术促进结肠上皮的吸收功能,其机制很可能是Wnt/β-catenin通路介导的肠上皮干细胞再生。     

Evaluation of intestinal absorption after longitudinal intestinal lengthening for short bowel syndrome

Purpose

The aim of this study was to answer if the longitudinal intestinal lengthening and tailoring (LILT) by Bianchi, modified by Aigrain, can allow the child to be weaned from parenteral nutrition (PN) and if the length of the bowel after the procedure can influence the results of the absorption test such as Schilling or d-xylose test.

Patients and Methods

We reviewed the files of 7 children who have had LILT from 1980 to 2003. We performed to explore 2 intestinal function tests: the d-xylose and the Schilling tests. Both were performed early (during the first year after the procedure) and late (during the second year) after the LILT. We used the χ² and Bartlett's correlation tests for statistical analysis.

Results

There were 6 boys and 1 girl. The surgical indication was short bowel syndrome with parenteral nutrition owing to multiple intestinal atresia (2 cases), severe necrotizing enterocolitis with volvulus (1 case), necrotizing enterocolitis (1 case), intestinal atresia with gastroschisis (2 cases), and volvulus owing to malrotation (1 case). The length of the bowel was significantly different before and after LILT (P < .0001). After LILT, the length of the bowel was significantly correlated with the percentage of PN on energy at 6 months (P = .02) and at 12 months (P = .001). Moreover, the length of the bowel after the procedure was significantly correlated with the results of the d-xylose test during the first year (P = .002) but not with the results after the second year. The length after lengthening influenced neither the results of the Schilling test during the first nor those of the second year after. Four patients were weaned from the PN 21 months in average after the LILT (57%); 1 was not because we had only a 2-month follow-up. The average follow-up was 111 (5 months; range, 4- 206).

Conclusion

Longitudinal intestinal lengthening and tailoring for short bowel syndrome is a good option to allow children to be weaned from the PN. The length of the bowel after the procedure can influence the absorption test such as d-xylose during the first postoperative year but not during the second and does not influence the Schilling test. We think it is not necessary to perform these tests during the follow-up of these patients.     

Oral absorption of tacrolimus in children with intestinal failure due to short or absent small bowel

We describe two children with intestinal failure due to short or absent small bowel who underwent isolated liver transplantation for liver disease related to parenteral nutrition. Both received reduced-size liver grafts whilst awaiting a suitable small bowel donor. Immunosuppressive therapy was based on oral tacrolimus and intravenous steroids. Therapeutic levels of tacrolimus were achieved at low dosage of 0.14–0.28 mg/kg per day. Median and mean blood tacrolimus levels were 9.9 and 13.7 ng/ml (range 4.9–42.3 ng/ml) in case 1 and 5.8 and 7.2 ng/ml (range 1–30 ng/ml) in case 2 before small bowel transplantation, respectively. Following small bowel transplantation, levels were 17.1 and 20.1 ng/ml (range 9.2– 30 ng/ml), with oral doses of 0.54–1.35 mg/kg per day. Both children died of adenovirus pneumonia, with functioning grafts. Our experience demonstrates that effective levels of immunosuppression can be achieved by oral administration of tacrolimus in children with short or absent small bowel. Received: 10 November 1998 Received after revision: 4 May 1999 Accepted: 19 July 1999     

胰高血糖素样肽-2对短肠大鼠残留小肠代偿的影响

目的研究胰高血糖素样肽-2(GLP-2)对短肠大鼠残留小肠形态及功能代偿的影响。方法将20只切除小肠75%的大鼠随机分成对照组和GLP-2组,术后1-5 d内自由进食。GLP-2组每日2次腹腔注射GLP-2(250μg·kg~(-1)·d~(-1))；对照组每日2次腹部皮下注射生理盐水0．5 ml；另设1组正常进食大鼠作空白对照。术后第6天行残留小肠黏膜形态学检测、细胞增殖核心抗原(PCNA)测定,钠葡萄糖共同转运体(SGLT1)和二肽转运体(PEPT1)的mRNA表达检测以及在体小肠循环灌流实验测定大鼠回肠的单位长度及单位重量的葡萄糖吸收率。结果GLP-2组残留小肠黏膜形态学指标、PCNA指数显著高于对照组；而小肠黏膜细胞凋亡显著低于对照组；残留回肠SGLT1和PEPT1的mRNA表达显著高于对照组；均P＜0．05。但两组灌洗段回肠每g湿重葡萄糖吸收率差异无统计学意义(P＞0．05)。结论GLP-2能刺激小肠黏膜上皮增生、抑制凋亡,促进短肠大鼠残留小肠黏膜的形态及功能代偿。     

Morphological and functional changes in the colon after massive small bowel resection

Purpose

Anecdotal evidence suggests that the colon plays an important role after small bowel resection (SBR). However, colonic changes have not previously been studied. The aim of this study was to characterize morphological and functional changes within the colon after SBR and elucidate the influence of diet complexity on adaptation.

Method

In study 1, 4-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4, and 6 weeks postoperation to allow analysis of early and late adaptation responses. Piglets received a polymeric infant formula (PIF).In study 2, SBR piglets received an elemental diet and were studied at 6 weeks postoperation and compared with SBR + PIF piglets from study 1. For both studies, immunohistochemistry was used to quantitate intestinal cell types. Changes in functional proteins were measured by Western blot, enteroendocrine/peptide YY (PYY), enterocyte/liver fatty acid binding protein (L-FABP), and goblet cells/trefoil factor 3 (TFF3).

Results

In study 1, early and late adaptation-related changes were observed after SBR. Early adaptation included increased numbers of enterocytes (P = .0001), whereas late adaptation included increased proliferative cell numbers (P = .02). Enteroendocrine, goblet, and apoptotic cells numbers were significantly elevated in the resected group at all time-points studied (P < .05). Functional changes included increased levels of L-FABP (P = .04) and PYY (P = .03). There was no change in TFF3 expression.In study 2, feeding with an elemental diet resulted in suboptimal adaptation as evidenced by reduced rate of weight gain and significant reductions in total cell numbers (P = .0001), proliferative (P = .0001) and apoptotic cells (P = .04), enteroendocrine cells (P = .001), and PYY expression (P .004).

Conclusion

These findings indicate that significant morphological and functional changes occur in the colon after massive SBR and that these occur as early and late adaptation responses. Elemental diet was associated with suboptimal adaptation suggesting an effect of diet complexity on colonic adaptation.     

短肠综合征患者血清瓜氨酸水平与小肠吸收面积和功能的相关性

目的研究短肠综合征患者血清瓜氨酸水平的变化及其与肠道面积及吸收功能的相关性。方法采用高效液相色谱法测定22例短肠患者（短肠组）和33例健康人（对照组）血清瓜氨酸水平。短肠患者残存小肠长度及直径采用X线造影检测，并测定短肠患者尿D-木糖排泄率和肠道蛋白吸收度。分析短肠患者血清瓜氨酸与残存小肠长度、面积、蛋白及D-木糖吸收的相关性。6例行肠康复治疗的患者测定康复治疗前后瓜氨酸、D-木糖及蛋白吸收水平的变化。结果短肠组血清瓜氨酸水平显著低于健康对照组[（5．94±2．65）比（16．87±5．97）μmol／L，P〈0．01]。短肠组患者血清瓜氨酸水平与残存小肠长度（r=0.82）及表面积（r=0.86）呈正相关，与尿D-木糖排泄（r=0.56）及肠道蛋白吸收（r=0.48）也呈正相关。6例行肠康复治疗的患者治疗后血清瓜氨酸水平、蛋白及D-木糖吸收均显著增加，但3者增加百分比之间并无相关。结论血清瓜氨酸水平与短肠患者的小肠吸收面积和吸收功能呈正相关，能反映短肠患者小肠功能和衰竭程度，是康复疗效的良好指标。     

Small bowel reversal procedure for treatment of the "short gut" baby

An increasing number of infants have undergone massive intestinal resection for various reasons: uncontrollable diarrhea, malabsorption, and failure to thrive makes these babies a difficult management problem and threatens their survival and later "quality of life." Five short gut babies have had a 3-cm small bowel reversal operation as part of the total salvage effort. It is recognized that very skilled care by dedicated personnel and parents, utilizing i.v. nutrition and special feeding techniques, is probably the most significant factor in achieving success with these babies. It is believed small bowel reversal helps in keeping these infants alive while their intestinal tract is making the adjustments necessary for long-term survival.