Serum and intestinal diamine oxidase activity during intestinal adaptation.

Diamine oxidase (DAO) is a cytoplasmic enzyme found primarily in the villus epithelial cells of the small intestine. Serum DAO levels have been evaluated as a potential marker of intestinal disease in a variety of disorders, including gut atrophy, ischemia, and inflammation. In this study serum and tissue DAO levels were evaluated during intestinal adaptation. Twenty dogs were divided into 4 groups: sham laparotomy (n = 5), and 25% (n = 5), 50% (n = 5), and 75% (n = 5) distal enterectomy. Serum DAO activity (basal or postheparin) was measured prior to and 2 days, 4 weeks, 8 weeks, and 12 weeks after operation. Tissue DAO and changes in intestinal length, mucosal protein content, and villus height were measured at sacrifice 12 weeks later. Intestinal remnant length and protein content increased significantly with 50 and 75% resection. Tissue DAO activity was significantly decreased with any enterectomy. Serum postheparin DAO activity was significantly greater than basal at all time points but there was no significant change in either basal or postheparin DAO levels at any time following resection. It is concluded that serum DAO levels are not changed during the early adaptive period following intestinal resection and thus would not be useful as a marker of this process. Tissue DAO levels were diminished during adaptation, suggesting that tissue DAO activity is influenced not only by mucosal mass but by cellular metabolism and the proliferative status of the mucosa.     

The effect of intestinal autotransplantation on serum diamine oxidase activity

Circulating levels of diamine oxidase (DAO), a mucosal enzyme found primarily in the small intestine, have been shown to reflect intestinal mucosal damage in a variety of disease states. Our aim was to assess the usefulness of both basal and postheparin DAO activity as a marker of intestinal allograft rejection by studying the influence of the nonrejection effects of intestinal transplantation on these activities. This separation of the immunological from all other effects of transplantation was achieved by studying 11 dogs who had undergone autotransplantation of the small intestine and 11 unoperated controls. Basal serum DAO activity increased during the first 3 postoperative days following autotransplantation (20.5 +/- 0.7 units/ml on Day 3 versus 6.9 +/- 4.1 units/ml preoperatively, P less than 0.05) but thereafter returned to control levels at 1 month and remained so for more than 18 months. Postheparin DAO activity was similar in both groups with a maximum increase between 15 and 60 min following heparin administration. There was no correlation between maximal DAO activity and time since operation in the transplant group. Intestinal DAO activity was similar to unoperated animals 18 months after autotransplantation. These findings suggest that postheparin serum diamine oxidase activity is not influenced by autotransplantation and thus, is a potential marker of graft rejection following intestinal allotransplantation.     

Serosal patching impairs intestinal adaptation following enterectomy.

Increasing intestinal absorptive surface by mucosal regeneration on serosal patched intestinal defects is a potential surgical treatment for the short bowel syndrome. We previously found in long-term studies that serosal patching in dogs undergoing 75% enterectomy was deleterious to intestinal adaptation and absorption. Our aim was to evaluate the effect of serosal patching on the early morphologic and functional changes in postresectional adaptation and to examine the role of polyamine metabolic pathways in this process. Five unoperated New Zealand white rabbits (GP I) served as controls. Twelve other rabbits underwent either 50% distal enterectomy alone (GP II) or simultaneously had two 2 x 5-cm full-thickness ileal defects patched with adjacent cecal serosa (GP III). Animals in GP II gained an average of 7.2 +/- 5.3% body weight, whereas GP III animals lost 5.6 +/- 9.0% body weight (P less than 0.05). Intestinal remnant length was significantly less in GP III 3 weeks postoperatively (66 +/- 11 vs 85 +/- 8 cm, P less than 0.05) as was mucosal protein content (4.1 +/- 1.8% vs 6.2 +/- 1.9%) but villus height was similar in GPs II and III (505 +/- 131 vs 508 +/- 110 microns). In vitro mucosal function was similar in all three groups. Crypt cell production rate was significantly lower while ornithine decarboxylase and diamine oxidase activity were higher in GP III compared to GP II. However, polyamine levels were similar in all three groups. Serosal patching impairs intestinal adaptation following massive enterectomy. This is due in part to a decrease in proliferative activity which is not directly related to altered polyamine levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intestinal diamine oxidase levels reflect ischemic injury

Mucosal diamine oxidase (DAO) decreases during intestinal ischemia and may be a useful marker of intestinal ischemic injury. Tissue DAO activity and histologic changes were studied in intestinal segments taken from the midpoint of the small intestine before and 2, 4, and 24 hr after manipulation of the intestinal blood supply in 24 mongrel dogs. Intestinal DAO activity decreased significantly (17 +/- 21% of control value) 24 hr after SMA ligation and was associated with abnormal histology (histology score 7.8 +/- 2.9 at 24 hr vs 0.3 +/- 0.5 at 0 hr). SMA occlusion for 2 hr resulted in a significant decrease in DAO activity (45 +/- 36% of control value) 4 hr after manipulation which returned to normal at 24 hr, as did the histologic injury. Ligation of both the mesenteric arteries and veins resulted in a more rapid decrease in DAO activity. Decreased DAO activity correlated with the extent of histologic injury. Intestinal ischemia is associated with decreased intestinal DAO activity, which is influenced by the mechanism and duration of intestinal ischemia.     

谷氨酰胺对短肠综合征大鼠残留小肠代偿作用的影响

目的观察谷氨酰胺对短肠综合征大鼠残留小肠代偿作用的影响.方法23只雄性SD大鼠切除80%小肠,随机分三组饮食组(n=8)术后自由进食;全胃肠外营养(TPN)组(n=8)输TPN标准液;谷氨酰胺(Gln)组(n=7)输TPN+Gln;正常大鼠8只,作为正常对照组.术后第7天,称体重,取回盲部淋巴结和门静脉血作细菌培养,取残留空肠和回肠进行组织学检查(包括光镜和电镜).结果饮食组和Gln组术后体重有明显差异饮食组、TPN组和Gln组回盲部淋巴结和门静脉血细菌培养阳性率无明显差别,但TPN组细菌培养阳性率高于Gln组;饮食组空肠粘膜绒毛高度(VH)和粘膜厚度(MT)、回肠粘膜VH均明显大于正常组;正常组空肠粘膜VH、MT明显大于TPN组,正常组回肠粘膜隐窝深度(CD)、MT明显大于TPN组;Gln组空肠和回肠粘膜VH、CD和MT明显大于TPN组.结论80%小肠切除后,残留小肠发生代偿性改变,食物刺激是残留小肠代偿的重要因素;但这种代偿不完全,补充TPN可维持机体生理平衡,TPN引起残留小肠粘膜萎缩;Gln可阻止TPN引起残留小肠粘膜萎缩,促进残留小肠代偿.     

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.     

Significance of the Extent of Intestinal Resection on the Outcome of a Short-bowel Syndrome in a Porcine Model

Aim of the study: Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published. Methods: A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis. Results: Only in the 100% group, we observed a persistent weight loss (13.6 ± 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 ± 1.0 μmol/L; 90% group 18.8 ± 1.0 μmol/L; 75% group 26.3 ± 1.4 μmol/L; all p < .05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 ± 4.9 mg/L; 90% group 50.0 ± 19.6 mg/L; 75% group 57.8 ± 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%). Conclusions: 75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation.     

Effect of transforming growth factor-alpha on intestinal adaptation in a rat model of short bowel syndrome

OBJECTIVE: TGF-alpha has recently been shown to stimulate enterocyte proliferation. In the present study we investigated the effect of TGF-alpha on enterocyte proliferation and loss via apoptosis and its effects on intestinal adaptation in a rat following massive bowel resection. METHODS: Male Sprague-Dawley rats underwent bowel transection and reanastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group) and were treated with intraperitoneal TGF-alpha (75 microg/kg) from the ninth postoperative day (SBS-TGF-alpha group). Parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. Statistical significance was determined by ANOVA with a P < 0.05 considered significant. RESULTS: SBS-TGF-alpha rats demonstrated a significant increase (vs SBS) in duodenal, jejunal, and ileal overall bowel and mucosal weights; ileal mucosal DNA and protein; and jejunal and ileal villus height. SBS-TGF-alpha rats also showed an increased cell proliferation index in jejunum (704 +/- 43 vs 499 +/- 63 BrdU-positive cells/10 crypts, P < 0.05) and ileum (715 +/- 84 vs 529 +/- 40 BrdU-positive cells/10 crypts, P < 0.05) and decreased apoptotic index in ileum (8.7 +/- 1.1 vs 21.8 +/- 3.2 apoptotic cells/1,000 villus cells, P < 0.05) compared to SBS animals. CONCLUSIONS: In a rat model of SBS, TGF-alpha enhances intestinal adaptation. Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis.     

Morphologic and nutritional responses to intestinal patching following intestinal resection

Growth of neomucosa has been investigated as a means to increase intestinal surface area in the short-bowel syndrome. Functional neomucosa grows over patched intestinal defects, but the effect of the patching procedure on absorption is unknown. The purpose of this study was to determine morphologic and nutritional responses to intestinal patching after resection. Fifteen dogs (13 to 19 kg) underwent either 75% resection of the small intestine (control group, n = 5), simultaneous resection and patching of the intestinal remnant with colon serosa (simultaneous group, n = 5), or resection with patching 12 weeks later (delayed group, n = 5). Caloric intake was standard in the three groups. Animals were killed 40 weeks after resection or patching. At that time, defects were 95% covered with neomucosa in both patched groups. Intestinal remnant length increased significantly in controls (139 +/- 20% initial length) compared to the simultaneous group (99 +/- 6%, p less than 0.05) but not to the delayed group (119 +/- 11%). Villous height of intestinal mucosa was greater in the control and delayed groups than in the simultaneous group (714 +/- 36 and 624 +/- 111 versus 535 +/- 54 micron, p less than 0.05). Fasting gastrin levels were significantly greater in patched animals than after resection alone (p less than 0.05). Intestinal transit by barium meal was significantly longer in patched animals (18 +/- 7 minutes versus 11 +/- 6, p less than 0.05). Body weight and serum albumin level were significantly lower in patched animals at death. Fecal weight, moisture, and fat excretion were significantly increased in the simultaneous group. Although intestinal patching results in the growth of neomucosa and prolonged transit time, it has a deleterious effect on absorption and nutritional status. In part, this may be related to inhibition of intestinal adaptation and gastric hypersecretion in patched animals.     

Absorption of orthotopically transplanted intestine in rats: evaluation of amino acid absorption

During the early phase of our intestinal transplant program, a low-lipid, amino acid-based feeding was employed for most recipients. However, relatively little is known regarding the amino acid absorption by a graft following intestinal transplantation. Sixty Wistar rats were randomly divided into two groups (n = 30). The animals received two-step orthotopic intestine transplantation (OIT), or the control; enterectomy with anastomoses. We measured mucosal Na(+)/K(+)-ATPase and intestinal absorption using stable isotope techniques in vivo. Compared with controls, mucosal Na(+)/K(+)-ATPase activity in OIT decreased by 38.3% and 38.4% at 2 and 4 weeks, and returned to baseline and control group values at 8 weeks. Glycine absorption decreased at 2 weeks and returned to baseline at 4 weeks in OIT compared with that in controls. These results suggested that absorption as assessed by mucosal Na(+)/K(+)-ATPase and glycine, returned to baseline at least 4 weeks after transplantation.     

Effect of artificial valves on intestinal adaptation in the short-bowel syndrome: an integrated study of morphological and functional changes in rats

Two-third-resections of the proximal or distal small bowel with and without artificial valves were performed in rats. Intestinal adaptation led to a significant increase in bowel diameter, villus height and villus diameter and consequently in absorptive mucosal surface area per unit of serosal area. Additional artificial valve construction did not affect the calculated mucosal surface area after proximal resection, while it significantly decreased the absorptive area by the occurrence of large, plump villi after distal resection. There was no change in small-intestinal absorption of water, glucose and electrolytes per unit mucosa with valve construction. DNA cytometry showed that artificial valves led to mucosal hyperplasia without hypertrophy. These morphological changes coincided with a significant increase in basal and stimulated gastrin release. The body weight was unchanged or even worse in the valve groups than after resection alone, despite a significantly prolonged transit time. Therefore, in our study, artificial valves did not result in functional improvements after small intestinal resections.     

Somatostatin analogue treatment inhibits post-resectional adaptation of the small bowel in rats

Post-resectional hyperplasia is the phenomenon in which residual small bowel increases in size and absorptive capacity after segmental enterectomy. This experiment studied the effect of somatostatin analogue therapy on the development of two structural parameters of post-resectional hyperplasia in rats subjected to 40% proximal small bowel resection. Octreotide acetate-treated rats failed to develop increased villus height (902 +/- 50 microns) relative to saline-treated rats (1,103 +/- 98 microns). Augmentation of residual intestinal weight was also significantly impaired in analogue-treated rats (92 +/- 3 versus 118 +/- 5 mg/cm). We conclude that somatostatin analogue treatment during the early postoperative period does impair the growth of residual bowel in rats. These findings raise concern regarding the use of this drug for postoperative patients who have undergone massive small bowel resection in whom the process of post-resectional adaptation may be critical to allow sustenance with enteral nutrition.     

Effect of sex and sex hormones on structural intestinal adaptation after massive small bowel resection in rats

Purpose

The gonadal steroids play a major role in the regulation of many functions. The purpose of the current study was to evaluate the effect of sex and sex hormones on intestinal adaptation in a rat model of short bowel syndrome (SBS).

Methods

In the first experiment, male and female Sprague-Dawley rats underwent bowel transection and re-anastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group). Relative changes in parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were measured on day 15 and were compared with respect to sex. In the second experiment, male rats were divided into 4 experimental groups: SBS rats, SBS castrated rats, SBS castrated rats treated with testosterone, and SBS castrated rats treated with estradiol. Parameters of intestinal adaptation were compared with respect to hormonal treatment. Statistical significance was determined by Student's t test and analysis of variance with P < .05 considered significant.

Results

Sex had minimal effects on intestinal adaptation. Both male and female rats showed a comparable increase in all parameters of intestinal adaptation. In the second experiment, castration led to significant decrease in bowel and mucosal weight, mucosal DNA and protein in both jejunum and ileum compared with SBS animals. Castrated rats also had lower jejunal villus height and crypt depth compared with SBS animals. Testosterone attenuated this negative effect of castration on bowel regrowth. Rats treated with testosterone showed a significant increase in bowel and mucosal weight, mucosal protein in both jejunum and ileum, mucosal DNA, villus height, and crypt depth in jejunum compared with castrated nontreated animals. Treatment with estradiol after resection and castration had minimal effect on bowel regrowth.

Conclusions

Bowel regrowth after massive small bowel resection is not sex-related. Depletion of androgens by castration inhibited intestinal adaptation. Testosterone has shown a strong stimulating effect on bowel regrowth.     

双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响

目的 探讨双歧三联活菌对体外循环心脏直视手术患者肠黏膜屏障功能的影响.方法 择期拟行体外循环下瓣膜置换术患者40例,年龄30～64岁,体重40～80 Kg,ASA分级Ⅱ或Ⅲ级,采用随机数字表法,将患者随机分为对照组(C组)和双歧三联活菌组(Y组),每组20例.Y组于术前7d开始,每日口服双歧三联活菌制剂(每片含活菌数0.5×107 CFU)4片,每日3次,连服7 d.分别于体外循环前(T1)、主动脉开放10 min(T2)、停体外循环即刻(T3)、术后2、6和18 h(T4～6)时采集中心静脉血样5 ml,采用紫外分光光度法测定血浆二胺氧化酶(DAO)活性和D-乳酸浓度,酶联免疫吸附法测定血浆IL-6和IL-10的浓度.结果 与T1时比较,两组其余时点血浆DAO活性和D-乳酸IL-6和IL-10浓度均升高(P＜0.05);与C组比较,Y组T2～5时血浆DAO活性和D-乳酸浓度降低,T4,5时血浆IL-6和IL-10浓度降低(P＜0.05).结论 双歧三联活菌可在一定程度上抑制炎性反应,改善体外循环心脏直视手术患者的肠黏膜屏障功能.

Abstract：

Objective To investigate the effects of probiotics on the plasma diamine oxidase (DAO) activity and D-lactate, IL-6 and IL-10 levels in patients undergoing open heart surgery under cardiopulmonary bypass (CPB) , trying to elucidate the mechanism of protective effect of probiotics against CPB- induced injury to intestinal mucosal barrier. Methods Forty ASA Ⅱ - Ⅲ patients of both sexes aged 30-64 yr weighing 40-80 kg undergoing open heart operation under CPB were randomized into 2 groups ( n = 20 each) : control group (group C) and probiotics group (group Y) . Group Y received Jinshuangqi (Bifid Triple Viable containing bifido-bacterium, lacto-bacillus, streptococcus thermophiles) 4 pills 3 times a day for 7 days before operation. Venous blood samples were taken from CVP line before operation (T1 ), at 10 min after aortic unclamping (T2 ) and at the end of CPB (T3 ) and at 2, 6, 18 h (T4,5,6) after operation for determination of plasma DAO activity and D-lactate, IL-6 and IL-10 levels.Results Plasma DAO activity, D-lactate, IL-6 and IL-10 levels were significantly increased after CPB was started at T2-6 as compared with the baseline values at T1 in both groups. Plasma DAO activity and D-lactate level were significantly lower at T2-5 , the plasma IL-6 level was significantly lower and plasma IL-10 level higher at T4,5 in group Y than in group C. Conclusion Probiotics can protect intestinal mucosal barrier in patients undergoing open heart surgery under CPB and attenuate inflammatory response.     

Serial transverse enteroplasty enhances intestinal function in a model of short bowel syndrome

OBJECTIVE/SUMMARY BACKGROUND DATA: Serial transverse enteroplasty (STEP) is a new intestinal lengthening procedure that has been shown to clinically increase bowel length. This study examined the impact of the STEP procedure upon intestinal function in a model of short bowel syndrome. METHODS: Young pigs (n=10) had a reversed segment of bowel interposed to induce bowel dilatation. Five pigs underwent a 90% bowel resection with a STEP procedure on the remaining dilated bowel while 5 served as controls and had a 90% bowel resection without a STEP procedure. Determinations of nutritional status, absorptive capacity, and bacterial overgrowth were conducted 6 weeks after resection. Statistical comparisons were made by 2-sample t test (significance at P<0.05). RESULTS: The STEP procedure lengthened the bowel from 105.2+/-7.7 cm to 152.2+/-8.3 cm (P<0.01). The STEP animals showed improved weight retention compared with controls (mean, -0.5%+/-1.8% body weight versus -17.6%+/-1.5%, P<0.001). Intestinal carbohydrate absorption, as measured by d-Xylose absorption and fat absorptive capacity as measured by serum vitamin D and triglyceride levels, were increased in the STEP group versus controls. Serum citrulline, a marker of intestinal mucosal mass, was significantly elevated in the STEP pigs compared with controls. None of the STEP animals but 4 of 5 control animals were noted to have gram-negative bacterial overgrowth in the proximal bowel. CONCLUSIONS: STEP improves weight retention, nutritional status, intestinal absorptive capacity, and serum citrulline levels in a porcine short bowel model. A salutary effect upon bacterial overgrowth was also noted. These data support the use of this operation in short bowel syndrome.     

The role of apoptosis during intestinal adaptation after small bowel resection

BACKGROUND/PURPOSE: Adaptation after small bowel resection (SBR) is characterised by a new set point in the balance of enterocyte proliferation and apoptosis. Apoptosis is gene directed. The authors hypothesised that the adaptive response is influenced positively by antiapoptotic gene products (eg, bcl-2 gene-produced protein). The authors tested this hypothesis by studying the effect of bcl-2 overexpression on intestinal adaptation after SBR. METHODS: Male bcl-2 transgenic mice, overexpressing bcl-2 in the small intestinal epithelium, and wild type control mice underwent either a 75% mid-SBR, or a sham operation. The 4 experimental groups consisted of resection wild type (n = 8), transection wild type (n = 6), resection bcl-2 transgenic (n = 8), and transection bcl-2 transgenic (n = 8). Seven days postoperatively small bowel was harvested; total weight, mucosal weight, and mucosal protein, DNA, and RNA content in jejunal and ileal tissue were determined to quantitate the hyperplastic response. RESULTS: Compared with sham-operated animals, SBR resulted in increased total jejunal weight; mucosal weight; and mucosal protein, DNA, and RNA content. Furthermore, in the SBR groups, the jejunal mucosal weight and mucosal protein and DNA content were significantly higher in the bcl-2 transgenic mice compared with the wild-type mice. No differences were observed between any of these parameters in the transection wild-type and transgenic mice. In the ileum, similar changes were observed. The differences between resected and transected wild-type mice were less pronounced, and only total ileal weight and mucosal protein content reached statistical significance. In the transgenic animals, all ileal variables, with the exception of mucosal RNA content, were significantly higher in the SBR group than in the transected group. SBR in the transgenic mice resulted in higher ileal mucosal weight and mucosal protein, DNA, and RNA content compared with the wild-type mice. CONCLUSIONS: The results show that the murine SBR model is a true representation of the process of adaptation after SBR. Furthermore, major components of the adaptive response, both in the jejunum and in the ileum, are significantly more pronounced in the bcl-2 transgenic mice than in the wild-type control animals. Thus, it can be concluded that intestinal hyperplasia after SBR is significantly enhanced by overexpression of the anti-apoptotic bcl-2 gene product. This finding should prompt further research on the effects of antiapoptotic interventions on adaptation after SBR.     

CXCL5 is required for angiogenesis,but not structural adaptation after small bowel resection

Purpose

Intestinal adaptation is the compensatory response to massive small bowel resection (SBR) and characterized by lengthening of villi and deepening of crypts, resulting in increased mucosal surface area. Previous studies have demonstrated increased villus capillary blood vessel density after SBR, suggesting a role for angiogenesis in the development of resection-induced adaptation. Since we have previously shown enhanced expression of the proangiogenic chemokine CXCL5 after SBR, the purpose of this study was to determine the effect of disrupted CXCL5 expression on intestinal adaptation.

Methods

CXCL5 knockout (KO) and C57BL/6 wild type (WT) mice were subjected to either a 50% proximal SBR or sham operation. Ileal tissue was harvested on postoperative day 7. To assess for adaptation, villus height and crypt depth were measured. Submucosal capillary density was measured by CD31 immunohistochemistry.

Results

Both CXCL5-KO and WT mice demonstrated normal structural features of adaptation. Submucosal capillary density increased in the WT but not in the KO mice following SBR.

Conclusion

CXCL5 is required for increased intestinal angiogenesis during resection-induced adaptation. Since adaptive villus growth occurs despite impaired CXCL5 expression and enhanced angiogenesis, this suggests that the growth of new blood vessels is not needed for resection-induced mucosal surface area expansion following massive SBR.     

Intestinal Knockout of Peroxisome Proliferator-Activated Receptor-Alpha Affects Structural Adaptation but not Liver Injury Following Massive Enterectomy

BackgroundResection-associated liver steatosis, injury, and fibrosis is a devastating complication associated with massive small bowel resection (SBR). Peroxisome proliferator-activated receptor-alpha (PPARα) is a key regulator of intestinal lipid transport and metabolism whose expression is selectively increased after SBR. Here we asked if attenuating intestinal PPARα signaling would prevent steatosis and liver injury after SBR.MethodsPparα was deleted selectively in adult mouse intestine using a tamoxifen-inducible Cre-LoxP breeding schema. Mice underwent 50% SBR. At 10 weeks post-operatively, metabolic phenotyping, body composition analysis, in vivo assessment of lipid absorption and intestinal permeability, and assessment of adaptation and liver injury was completed.ResultsPparα intestinal knockout and littermate control mice were phenotypically similar in terms of weight trends and body composition after SBR. All mice demonstrated intestinal adaptation with increased villus height and crypt depth; however, Pparα intestinal knockout mice exhibited decreased villus growth at 10 weeks compared to littermate controls. Liver injury and fibrosis were similar between groups as assessed by serum AST and ALT levels, Sirius Red staining, and hepatic expression of Col1a1 and Acta2.ConclusionsInducible intestinal deletion of Pparα influences structural adaptation but does not mitigate liver injury after SBR. These findings suggest that enterocyte PPARα signaling in adult mice is dispensable for resection-induced liver injury. The results are critical for understanding the contribution of intestinal lipid metabolic signaling pathways to the pathogenesis of hepatic injury associated with short bowel syndrome.     

慢性肾衰竭大鼠肠道通透性及损伤的研究

目的 探讨慢性肾衰竭（CRF）大鼠肠道通透性及损伤的变化。 方法 雄性SD大鼠20只分为CRF组（n=10）和对照组（n=10）,采用5/6肾切除制备CRF大鼠模型,定期监测血生化至模型成功建立。术后第12周,大鼠禁食12 h后灌饲含有1 g乳果糖（L）和0.5 g甘露醇（M）的测试液4 ml,收集大鼠口服测试液后6 h内的全部尿液,采用高压液相色谱-示差法（HPLC-RID）,检测尿液排泄率比值（L/M）,评估大鼠肠黏膜通透性水平;HE染色观察各组大鼠小肠黏膜光镜下的形态（肠黏膜绒毛高度、肌层厚度、绒毛数量）并行组织学损伤评分。 结果 CRF组大鼠尿L/M比值高于对照组（1.75±0.11 比 1.20±0.06,P < 0.01）;其肠黏膜绒毛高度、肌层厚度显著高于对照组（P < 0.01）,绒毛数量显著低于对照组（P < 0.01）。CRF组大鼠肠道病理组织学评分显著高于对照组（1.00±0.71比0,P < 0.01）。 结论 CRF大鼠肠道通透性增加,并且伴有不同程度的肠道损伤。     

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.