The influence of intestinal resection on the growth of intestinal neomucosa

Intestinal resection stimulates proliferative activity in the intestinal remnant. The aim of this study was to determine the influence of intestinal resection on the growth of intestinal neomucosa. Forty-eight New Zealand white rabbits had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 24) served as controls. Group II (n = 24) underwent simultaneous 50% enterectomy. Neomucosal coverage was significantly greater in Group II at 1 week (36 +/- 11% vs 67 +/- 9%, P less than 0.05) and 2 weeks (94 +/- 2% vs 99 +/- 1%, P less than 0.05), but was similar at 3 and 4 weeks. There was significantly more neomucosa at 1 week in the animals that underwent resection (134 +/- 55 mm2 vs 199 +/- 54 mm2, P less than 0.05). Degree of patch contraction, glucose uptake, and disaccharidase activities were similar in each group. Ornithine decarboxylase activity and crypt cell production rate were significantly greater at 1 week in the animals that underwent resection. Intestinal resection results in an early increase in neomucosal growth and increased proliferative activity. Since contraction of the patches occurs to a similar extent in both groups, the total amount of neomucosa was not increased. Thus, performing patching at the time of resection is not necessary for optimal growth.     

Growth of neomucosa after intestinal resection

The growth of neomucosa over patched intestinal defects may prove useful in the short-bowel syndrome. This study was done to determine if the timing of intestinal patching with respect to intestinal resection affects neomucosal growth. Twelve dogs underwent 75% intestinal resection, with intestinal patching done either simultaneously or 12 weeks later. Energy intake, final body weight, albumin level, and length of remnant patched were similar in both groups. Forty weeks after patching, neomucosal coverage of the defect (95.2% +/- 2.0% vs 94.2% +/- 1.6%), neomucosal surface area (36.2 +/- 4.5 vs 31.8 +/- 2.9 cm2), and patch size (56.2% +/- 6.8% vs 51.9% +/- 9.7%) were similar in both the simultaneous and delayed groups, as were villus height of neomucosa and disaccharidase activity. Neomucosal growth is similar whether intestinal patching is performed simultaneously or 12 weeks after resection. Intestinal patching is not indicated at the initial intestinal resection.     

Growth of intestinal neomucosa on prosthetic materials

The short bowel syndrome is a potential complication of the surgical management of diseases of the large and small intestine. Recently methods have been examined for expanding the small bowel absorptive area using prosthetic materials. We investigated the feasibility of growing intestinal mucosa on prosthetic patches and tubes. Ileal defects were patched with a 2 X 5-cm patch of either Dacron (n = 15), polyglycolic acid mesh (PGA) (n = 9), or polytetrafluroethylene (PTFE) (n = 5) prosthesis in New Zealand white male rabbits. Gross and microscopic analysis at 2, 4, and 8 weeks revealed that the serosal surface was covered with neomucosa by 4 weeks. Dacron and PTFE grafts were either minimally attached or extruded and PGA grafts had dissolved. At 8 weeks, none of the patches were present but with all three materials the resultant area of neomucosa was only 15% of the original defect. The neomucosa was functional as determined by glucose uptake and disaccharidase activity. Three centimeter Dacron tubes were interposed in the distal ileum of 10 rabbits and in a bypassed ileal segment in 11 rabbits. There was an 80% mortality within 2 weeks, and no evidence of neomucosal growth. Although prosthetic patches support the growth of functional neomucosa, there is a minimal increase in the final surface area. The type of prosthesis did not influence the outcome. The use of Dacron tubes is associated with high mortality and no neomucosal growth. The use of prosthetic materials is not likely to be useful in the clinical management of the short bowel syndrome.     

The influence of serosal patch size on the growth of small intestinal neomucosa

Several factors might affect the growth of neomucosa after serosal patching of small intestinal defects. Often only short segments of small intestine can be patched because of limited serosal surface and anatomic factors. The purpose of this study was to determine the influence of patch size on neomucosal growth. Twenty male New Zealand white rabbits underwent patching with colon serosa of either a 2 X 15-cm distal ileal defect (n = 10) or three 2 X 5-cm ileal defects (n = 10). There was significantly greater coverage of the patched defect by neomucosa in the triple patch group (99.4% vs 93.1% P less than 0.005) and significantly more of the smaller defects were completely covered by neomucosa than the larger defects (12 of 15 vs 0 of 5, P less than 0.05) at 8 weeks. The final area of the defect was 27.5 and 32.8% of the initial patched area respectively for the single and triple patches. Microscopically there was no difference in villous height or crypt depth, but crypt density was significantly greater in the triple group (207 +/- 11 vs 186 +/- 17 crypts/mm, P less than 0.05). In vitro glucose uptake and disaccharidase activity were similar in both groups. Patching multiple small intestinal defects results in more rapid neomucosal growth than a single large defect of the same surface area. This might be due to a greater circumference exposed to surrounding normal mucosa with a resultant increase in crypt density. Since function and villous development of the neomucosa are similar, multiple patches should result in a greater increase in absorptive capacity.     

The maturity of intestinal neomucosa: integrin expression and ultrastructural aspects

Background/purpose

The maturity of neomucosa growing on a serosal surface for the treatment of short bowel syndrome still is questionable. The aim of this study was to evaluate the intestinal neomucosa to assess its histologic maturity.

Methods

A 6-cm-long isolated ileal segment (IS) was prepared in 8 Wistar albino-type rats. The IS was divided from the antimesenteric side, and 2 intestinal tubes were established, which shared a common wall and a common pedicle. After ileal biopsy sampling for the control group (CG), the IS was fashioned into a mucous fistula. Eight weeks later, all the rats were killed, and the ISs were investigated for neomucosal growth. Sections were prepared with periodic acid shift (PAS) and H & E staining for light microscopy. They also were evaluated by transmission electron microscopy. The microscopic morphology of the 2 groups was evaluated. Immunohistochemical staining was performed to show the expression of the tissue β1, α3 and α2β1 integrin subunits of both the neomucosa (NS) and control group (CG) segments.

Results

Sections of the NS showed a well-arranged columnar epithelial cell layer with goblet cells that were generally located superficially and with a complete basement membrane. Under the electron microscope, the sections from the NS group showed an epithelial cell layer with proper microvilli of the same height, although they were shorter than those of the CG, and tight intercellular junctions between the epithelial cells. Significant differences between the NS and CG groups were found in the measurements of villus width at base, microvillus surface, and microvillus height. The lamina propria consisted of rich collagen fibers and active fibroblasts in the NS group. In the immunohistochemical staining, although β1 integrine showed a dense distribution (+++) in the lamina propria, particularly localizing at the depth of the tunica mucosa layer, α3 integrin was observed to have a less dense immunoreactivity (++) in both groups. The expression of α2β1 integrin showed slight and dispersed (+) staining.

Conclusions

The NS showed histologic maturity and ultimate structural similarity with the native small bowel mucosa, which provides strong indirect evidence for the proper functioning of the neomucosa.     

糖皮质激素对大鼠肠屏障功能的损害

目的探讨器官移植术后早期应用大剂量糖皮质激素对肠屏障功能的影响。方法将56只Wistar大鼠随机分为免疫抑制组和阴性对照组。免疫抑制组大鼠每日腹腔注射甲泼尼龙100mg/kg,1次/d,阴性对照组每日腹腔注射生理盐水1ml。用药后,每组在全麻下按4个时间点(0、3、5、7d)无菌操作获取血液、肠系膜淋巴结、肠内容及回肠组织,分别用于检测血浆D乳酸、血浆二胺氧化酶(DAO)、肠道菌群微生态、肠系膜淋巴结淋巴细胞凋亡指数及某些脏器细菌培养等。结果免疫抑制组与阴性对照组比较,从用药后第3d开始,各时间点血浆D乳酸以及DAO均显著升高(P<0.01或P<0.05),肠道菌群却无明显改变(P>0.05),肠系膜淋巴结淋巴细胞凋亡指数显著升高(P<0.01);第7d时脏器细菌培养阳性率较阴性对照组明显升高(P<0.05)。结论甲泼尼龙能够造成大鼠肠屏障功能的损害,使肠屏障通透性升高。     

Comparison of techniques for growing small bowel neomucosa

Small bowel neomucosa has been grown on a variety of surfaces. The purpose of this study was to compare the rate of growth and function of neomucosa on colon serosa (CS) and abdominal wall muscle (AM) in New Zealand white rabbits. The terminal ileum was incised for 5 cm and patched with either adjacent CS (23 animals) or AM (19 animals) to create a 2 X 5-cm defect. Gross and histologic examinations of the specimens at 1, 2, 4, and 8 weeks revealed that the rate of growth was similar in both groups. There was minimal lateral ingrowth at 2 weeks, nearly complete coverage of the defects at 4 weeks, and complete coverage of the defect at 8 weeks in more than 85% of animals with mature villi and muscularis mucosae. The ileal diameter at the site of patching increased in both groups from 11.9 +/- 2.6 to 16.3 +/- 3.2 mm in the CS group and 11.3 +/- 2.5 to 15.1 +/- 1.8 mm in the AM group (P less than 0.01). Glucose uptake was similar in both groups being 65.4 +/- 24.1% of control in the CS group and 73.9 +/- 29.8% in the AM group. Brush border enzyme activity of sucrase, maltase, and lactase was similar to controls in the AM group but in the CS group activity of sucrase and maltase were significantly less than controls (P less than 0.01). Average body weight was increased postoperatively in both groups. There was one anastomotic leak in each group and two cases of partial intestinal obstruction in the abdominal wall group.(ABSTRACT TRUNCATED AT 250 WORDS)     

γ干扰素对缺氧肠上皮屏障功能影响及其机制

目的 观察γ干扰素(IFN-γ)对缺氧肠上皮细胞屏障功能的影响,探讨其分子机制.方法 对HT-29细胞进行缺氧及IFN-γ处理,检测跨上皮电阻(TER)、缺氧诱导因子-1α( HIF-1α)蛋白及肠三叶因子(ITF)、黏蛋白3(mucin-3)、CD73、CD55、血小板活化因子受体(PAFR) mRNA表达的变化.结果 缺氧+ IFN-γ使TER明显下降(较常氧和缺氧下降33.8％、28.3％),使HIF-1α蛋白较缺氧降低72.1％,使ITF、mucin-3、CD73、CD55、PAFR mRNA分别较缺氧降低53.3％、31.1％、74.6％、62.4％,但PAFR mRNA水平两组间差异无统计学意义(P＞0.05).结论 IFN-γ能使缺氧肠屏障功能降低,与IFN-γ使HIF-1α蛋白降低,并抑制HIF-1α下游的肠屏障调节因子密切相关.     

Effect of transforming growth factor beta and basic fibroblast growth factor on steroid-impaired healing intestinal wounds.

A longitudinal intestinal wound model in the pig was used to assess the effect of parenteral steroids (betamethasone 12 mg 50 kg-1 intramuscularly twice daily) on breaking load. Steroid treatment significantly decreased the breaking load of wounds in the ileum and colon in comparison with wounds from saline-treated animals. In a further group of animals receiving steroids, paired longitudinal wounds were constructed. One wound of a pair was treated with a local application of transforming growth factor beta (TGF-beta) (5 micrograms per wound) or basic fibroblast growth factor (5 micrograms per wound) in a collagen suspension. The other wound was treated with a collagen suspension alone. Ileal wounds treated with TGF-beta were significantly stronger than collagen-treated controls at 7 days. The steroid-induced impairment of breaking load in intestinal wounds is partially reversed by a local application of TGF-beta in a collagen suspension at the time of surgery.     

重组人生长激素对大鼠肠缺血再灌注后肠壁组织T淋巴细胞亚群和浆细胞的影响

目的　探讨肠道屏障功能损害时应用重组人生长激素(rhGH )对肠道免疫屏障中肠黏膜及固有层内T淋巴细胞亚群和浆细胞的影响。方法　将60只Wistar大鼠雌雄各半随机分为实验组和对照组,按实验天数(2、4、6d)又各分为3组,每组10只,以肠缺血再灌注模型造成肠道屏障功能损害的病理现象,实验组给与rhGH (每日1.3 3U/kg体重) ,观察回肠末端黏膜固有层内CD8+、CD4+、CD3 +T淋巴细胞数及IgA浆细胞的数量变化。结果　(1)实验组CD8+、CD4+、CD3 +T及IgA浆细胞第6天与第2、4天比较数量显著增多,差异有统计学意义(P <0 .0 5 )。(2 )实验组与对照组第6天,CD8+、CD4+T及IgA浆细胞的数量实验组均高于对照组,差异有统计学意义(P <0 .0 5 )。(3 )CD4+/CD8+比值第2天两组差异有统计学意义(P <0 .0 5 )。结论　肠道屏障功能损害时应用重组人生长激素能够调节肠黏膜的免疫屏障,其作用时间在第6天可能最明显     

生长激素对肝大部切除术后鼠肠黏膜的保护作用

目的: 探讨鼠肝大部切除术后生长激素对肠黏膜屏障的保护作用,为临床使用重组人生长激素保护肠黏膜提供实验依据.方法: 90只SD大鼠随机分为对照组、生理盐水(normal saline,NS)组和生长激素(recombinant human growth hormone,rhGH)组,后两组切除肝左叶和右叶;各组连续用药6 d,分别于术后第1,2,3,5和10天取回肠组织行光镜形态学观察及图像分析检测肠黏膜厚度和绒毛高度,并对回肠黏膜上皮细胞行核增殖抗原(proliferate cell nucleus antigen,PCNA)免疫组织化学测定;取心脏血4~6 ml,检测内毒素.结果: 肝大部分切除术后第1,2天,内毒素明显升高,而rhGH组与对照组无明显差异.术后第3,5天,回肠黏膜明显萎缩,绒毛变薄;黏膜上皮细胞PCNA明显下降(P<0.01).应用rhGH 3 d后,回肠绒毛高度、黏膜厚度和PCNA度均增加(P<0.01);术后第5天,达到对照组水平.结论: 肝大部分切除术后肠黏膜屏障受损,应用rhGH可保护肠黏膜屏障,减少血浆内毒素水平.     

大鼠急性胰腺炎反应中脾脏对肠屏障功能的影响

目的　探讨脾脏在大鼠急性胰腺炎(AP)病程中对肠屏障功能的影响。方法　随机将大鼠分成4组:假手术组,AP组,脾切除组,脾切除+AP组。手术后2 4h检测各组血清TNF α,IL 1β,IL 6及IL 1 0水平,术后2d测肠细菌移位率,并取末段回肠行光镜及透射电镜观察肠黏膜受损情况。结果　脾切除+AP组TNF α,IL 1β,IL 6及IL 1 0值分别为3. 0 6±3. 6 1, 1 6. 4 6±5. 5 2, 19. 90±6. 8 9, 6. 9 4±3. 9 3;AP组的测得值分别为1 9. 9 3±2. 3 8, 4 2. 7 9±4. 3 1, 2 0. 1 9±3. 3 5, 3 9. 2 8±1 2. 6 9。脾切除+AP组TNF α,IL 1β及IL 1 0的值显著低于AP组(P < 0. 0 5 ),脾切除+AP组细菌移位率为4 0%显著低于AP组9 3. 3% (P< 0. 0 5 )。脾切除+AP组肠黏膜上皮仅轻微水肿,肠黏膜基本完整,而AP组肠黏膜上皮水肿明显,绒毛坏死,上皮细胞变性,炎性细胞浸润及细菌移位。结论　脾脏在急性炎症反应中,可明显促进炎性介质的产生和释放,加重炎症反应。脾脏切除后可减少促炎因子的产生和释放,肠黏膜受损减轻,细菌移位率下降。     

受体低氧预适应后肠黏膜改变对大鼠移植肝的影响

目的:研究低氧预适应对肠道黏膜屏障的作用以及对移植肝再灌注损伤的影响.方法:88只SD大鼠分为原位肝移植组(A组)、受体低氧预适应组(B组)和假手术组(C组)、A、B组均行原位肝移植.术后2 h检测大鼠血清肝功能和内毒素水平、肝组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量,观察肝、肠组织细胞形态学改变以及3d和1周存活率.结果:B组肝功能损害与A组相比明显降低(P<0.01),MDA含量、血清内毒素明显低于A组(P<0.01),SOD活性明显高于A组(P<0.01);B组肝细胞结构改变较小,肠黏膜上皮损伤较轻;术后1周存活率B组较A组高(P<0.01).结论:受体低氧预适应能够保护肠黏膜屏障,减轻移植肝再灌注损伤.     

Effect of postoperative hemosorption on pulmonary function in patients with acute intestinal obstruction

The effect of postoperative hemosorption (HS) on the pulmonary functions in 55 patients with acute ileus was studied. The severity of the state of the patients was conditioned by intoxication leading to ++over-stress of the non-respiratory pulmonary functions and development of I-II stage acute respiratory failure. HS contributes to detoxication of an organism, but is accompanied by the mean 30-35% loss of the oxygen on the adsorbent resulting in development of arterial hypoxemia. Thus, HS should be added with spontaneous breathing with positive pressure at the end of expiration.     

Effect of infused vasoactive intestinal peptide on airway function in normal subjects.

Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.     

重组人生长激素对大鼠肠道缺血再灌注后肠壁组织T淋巴细胞亚群和浆细胞凋亡的影响

目的探讨肠道屏障功能损害时应用重组人生长激素（rhGH）对肠道免疫屏障中肠黏膜及固有层内T淋巴细胞亚群和浆细胞凋亡的影响。方法将60只Wistar大鼠雌雄各半随机分为实验组和对照组，按实验天数又各分为3组，每组10只，以肠缺血再灌注模型造成肠道屏障功能损害的病理现象，实验组给予rhGH每日（1．33U／kg体重），采用免疫组织化学双染法观察回肠末端黏膜固有层内CD8^＋、CD4^＋、CD3^＋T淋巴细胞数及IgA浆细胞的凋亡数量变化。结果（1）对照组CD3^＋T淋巴细胞及IgA浆细胞的凋亡数量第6天明显高于第2、4天。差异有统计学意义（P〈0．01）。（2）实验组CD8^＋、CD4^＋T淋巴细胞的凋亡数量第6天明显低于第4天，差异有统计学意义（P〈0．01）。（3）实验组与对照组相比第2、4、6天IgA浆细胞的凋亡数量均明显减少。差异有统计学意义（P〈0．01）。实验组与对照组相比大鼠第2天CD8^＋、CD4^＋、CD3^＋T淋巴细胞的凋亡数量均减少，差异有统计学意义（P〈0．05，P〈0．01）。结论肠道屏障功能损害时应用重组人生长激素能够减少肠道免疫细胞的凋亡数量，对IgA浆细胞作用最明显。可能的作用时间在第6天。     

Aberrant pancreas with a double intestinal location

The authors report one exceptional case of aberrant pancreas with a double intestinal location (jejunum and Meckel's diverticulum) in a thirty-year-old patient. Digestive haemorrhage and the abdominal colic were the revealing clinical signs. The enteroscopy guided by the enteroscanner, was the indicated complementary investigation for the preoperative diagnosis. The research of other locations during the operation should be systematic.     

参附汤预先给药对内毒素血症大鼠肠黏膜屏障功能的影响

目的 评价参附汤预先给药对内毒素血症大鼠肠黏膜屏障功能的影响.方法 选择健康成年雄性SD大鼠24只,4～6月龄,体重180～220 g.采用随机数字表法,将其分为3组(n=8):正常对照组(C组)、内毒素血症组(E组)和参附汤预先给药组(S组).采用尾静脉注射脂多糖(LPS) 10mg/kg建立内毒素血症模型.建模前30 min,E组和S组分别腹腔注射生理盐水和参附汤5ml/kg.于建模后2h时取腹主动脉血样,采用ELISA法检测血浆TNF-α、IL-6、肠-脂肪酸结合蛋白(i-FABP)和D-乳酸(D-lac)浓度;取远端回肠,采用免疫组化法检测肠黏膜上皮细胞间紧密连接蛋白(ZO-1)表达,HE染色,光镜下观察肠黏膜病理学结果,并行Chiu评分.结果 与C组比较,E组和S组血浆TNF-α、IL-6、i-FABP和D-lac浓度升高,肠黏膜Chiu评分升高,肠黏膜上皮细胞间ZO-1表达下调(P＜0.05).与E组比较,S组血浆TNF-α、IL-6、i-FABP和D-lac浓度降低,肠黏膜Chiu评分降低,肠黏膜上皮细胞间ZO-1表达上调(P＜0.05).结论 参附汤预先给药可减轻内毒索血症大鼠肠黏膜损伤,保护肠黏膜屏障功能,其机制与抑制全身炎性反应有关.