Increases in nup475 and c-jun are early molecular events that precede the adaptive hyperplastic response after small bowel resection.

OBJECTIVE: The authors determined whether increases of nup475 and c-jun gene expression occur after small bowel resection and whether these changes are specific to the gut. SUMMARY BACKGROUND DATA: Massive small bowel resection (SBR) is characterized by adaptive proliferation of the remaining gut mucosa; the molecular signals responsible for this adaptive hyperplasia are unknown. Increases in the "immediate-early genes" nup475 and c-jun are noted in some proliferating tissues; however, alterations in the expression of these genes have not been described in the gut after SBR. METHODS: Rats underwent either a 70% proximal SBR or intestinal transection with reanastomosis (SHAM) and were then killed over a time course (0.5, 2, and 24 hours). The ileum, duodenum, colon, and kidneys were removed and RNA was extracted for Northern hybridization. RESULTS: The authors found that steady-state mRNA levels of both nup475 and c-jun were increased 81% and 62%, respectively, in the ileal remnant at 2 hours in rats after SBR compared with the SHAM group. In addition, nup475 was increased 101% in the duodenum at 24 hours and 31% in the colon at 0.5 hours in rats after SBR. In contrast, neither gene was increased in the kidney. CONCLUSIONS: Increases in steady-state levels of nup475 and c-jun are limited to the gut after SBR, and the timing and magnitude of these changes differ, depending on the gut segment. Finally, the rapid and nutrient-independent increases of nup475 and c-jun suggest an important role for these genes as early molecular signals that participate in the adaptive hyperplasia occurring in the gut remnant after SBR.     

Trophic response of gut and pancreas after ileojejunal transposition.

OBJECTIVE: The authors determined whether ileojejunal transposition (IJT) stimulates the growth of the pancreas or the nontransposed segment of small intestine, and ascertained whether this trophic effect is altered by the location of transposed gut segment. SUMMARY BACKGROUND DATA: Transposition of the ileum to the proximal small intestine stimulates a marked mucosal growth of the transposed ileal segment; the cellular mechanisms responsible for this adaptive hyperplasia are not known. METHODS: The distal quarter of the small intestine (distal ileum) was transposed into the proximal (Type I), middle (Type II), or distal (Type III) portions of the remaining small intestine. On postoperative day 28, the pancreas and scraped mucosa from the segments of transposed ileum, proximal ileum, and duodenum were obtained, weighed, and examined for DNA and protein content. RESULTS: All types of IJT increased mucosal weight and DNA content of the transposed ileum. Types I and II IJT produced a significant proliferation of the pancreas and mucosa of the duodenum and proximal ileum. The magnitude of proliferative increases was greatest in Type I IJT. CONCLUSIONS: Ileojejunal transposition appears to be an excellent model to examine the mechanisms by which intestinal epithelial cells proliferate in response to luminal nutrients or humoral factors.     

Differential effects of gut hormones on pancreatic and intestinal growth during administration of an elemental diet.

Liquid elemental diets (ED) will, in time, cause atrophy of the gut. Pentagastrin (PG), neurotensin (NT), and bombesin (BBS) are peptides that have trophic effects on the gut of normal rats. This study examined the effect of these three agents on gut atrophy produced by ED. Four groups of rats were given an ED and injected with either saline (control), PG (250 micrograms/kg), NT (300 micrograms/kg), or BBS (10 micrograms/kg) subcutaneously every 8 hours for 5 or 10 days. A fifth group was fed rat chow ad libidum. The rats were killed on day 6 or 11; the pancreas and segments of small intestine were removed. Atrophy of ileal mucosa was apparent on days 6 and 11, and atrophy of jejunal mucosa was manifest by day 11. Bombesin prevented jejunal mucosal atrophy and significantly increased ileal mucosal growth (compared with control). Neurotensin prevented the jejunal, but not the ileal, mucosal atrophy produced by ED. Pentagastrin had no effect on gut mucosa. Bombesin and PG, but not NT, stimulated pancreatic growth. Neurotensin stimulates pancreaticobiliary secretions (PBS), which are known to stimulate gut growth. Jejunoileal bypass was performed to determine whether trophic effects of NT on gut mucosa were mediated through stimulation of PBS. After 1 week treatment, animals were killed and segments of intestine removed. As expected NT was trophic for gut mucosa in continuity with the luminal stream; furthermore NT produced significant stimulation of growth of gut mucosa in the bypassed segment. We conclude that both BBS and NT are trophic for intestinal mucosa of rats given ED; both agents have a more pronounced effect on jejunum. The trophic effect of NT is mediated, in part, by a mechanism unrelated to stimulation of PBS. Bombesin and NT may have important regulatory functions in the adaptive growth of small bowel mucosa and in the maintenance of gut mucosal integrity.     

Effect of aging on the adaptive and proliferative capacity of the small bowel

Our society is aging at a rapid rate; the effects of aging on physiologic functions (e.g., small bowel adaptation) are poorly understood. The purpose of this study was to determine the ability of the aged small bowel mucosa to adapt after resection. Young (2-month-old) and aged (24-month-old) F344 rats underwent massive (70%) proximal small bowel resection (SBR) or sham operation; rats were killed at 9 or 16 days after surgery. The remnant small bowel and corresponding sham segments were harvested, weighed, and analyzed for DNA content and villus height. To determine whether the adaptive response after SBR could be enhanced, aged rats underwent SBR or sham operation and were treated with either neurotensin or saline solution (control). SBR resulted in adaptive hyperplasia in the remaining small bowel remnant in both young and aged rats at 9 and 16 days compared with sham animals. At 9 days, significant increases were noted in weight, villus height, and DNA content of the distal remnant in young and aged rats after SBR; the increases were similar in both young and aged rats. At 16 days, both young and aged rats displayed significant increases in remnant weight after SBR. Administration of neurotensin increased the weight of the remnant intestine in aged rats after SBR compared with saline treatment. Our findings demonstrate that aged small bowel mucosa exhibits a proliferative and adaptive capacity in response to SBR that was similar to that of the young animals. In addition, neurotensin administration enhanced the normal adaptive response of the small bowel in aged rats, providing further evidence that neurotensin may be therapeutically useful to augment mucosal regeneration in the early periods after massive SBR. Presented at the Forty-Third Annual Meeting of The Society for Surgery of the Alimentary Tract, San Francisco, California, May 19–22, 2002 (poster presentation), and published as an abstract in Gastroenterology 2002;123(Suppl):20. Supported by grants R37 AG10885, P01 DK35608, and T32 DK07639 from the National Institutes of Health and by a Jeane B. Kempner Scholars Award (R.P.T.).     

Prostaglandin E1 maintains structural integrity of intestinal mucosa and prevents bacterial translocation during experimental obstructive jaundice.

The absence of bile in the gut lumen induces mucosal injury and promotes bacterial translocation (BT). Prostaglandin E (PGE) has a protective effect on the mucosal layer of the alimentary tract. We hypothesize that PGE1 may prevent BT by its beneficial action on the mucosa of the small bowel. Thirty Wistar albino rats were divided equally into 3 groups; Group 1 (control) underwent sham laparotomy, group 2 obstructive jaundice (OJ) and group 3 (OJ + PGE1) underwent common bile duct (CBD) ligation and transection. Groups 1 and 2 received; 1 mL normal saline and group 3 received 40 mg of the PGE1 analogue misoprostol dissolved in 1 mL normal saline administered by orogastric tube once daily. After 7 days, laparotomy and collection of samples for laboratory analyses were performed, including bacteriological analysis of intestine, mesenteric lymph nodes (MLNs), and blood, and histopathologic examination of intestinal mucosa to determine mucosal thickness and structural damage. Serum bilirubin and alkaline phosphatase levels confirmed OJ in all animals with CBD transection. The mucosal damage score was significantly reduced in jaundiced animals receiving PGE1 compared to jaundiced controls (2.15 +/- 0.74 vs 5.3 +/- 0.59; p < .00001) and mucosal thickness was greater (607 +/- 59.1 microm vs. 393 +/- 40.3 microm; p < .00001). The incidence of BT to MLNs decreased from 90% to 30% (p < .02) when jaundiced rats received PGE1. PGE1 treatment reduced the detection rate of viable enteric bacteria in the blood from 60% to 10% (p < .057). We conclude that administration of PGE1 provides protection against OJ-induced atrophy and damage of intestinal mucosa, and thereby prevents translocation of enteric bacteria to underlying tissues.     

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.     

Burn-induced transcriptional regulation of small intestinal ornithine decarboxylase.

The mechanisms responsible for gut repair after burn injury have not been established. Polyamines are required for eukaryotic cell growth and differentiation. The enzyme ornithine decarboxylase (ODC) catalyzes the rate-limiting step in polyamine biosynthesis. The role of ODC activity in repair of injured small bowel mucosa after burns has not been investigated. This study examined the effects of burn injury on gut mucosal mass and regulation of ODC gene expression and ODC activity in small bowel mucosa. After an overnight fast, 18 male Sprague-Dawley rats (250 to 300 g) were randomized into sham, 20% burn, or 60% burn groups. We measured ODC activity, mucosal weight, deoxyribonucleic acid (DNA) content, and protein content in proximal and distal small bowel mucosa at postburn intervals of 0, 3, 12, 24, and 48 hours. Gut mucosal ODC messenger ribonucleic acid (mRNA) levels were determined. Burn injury caused significant atrophy of the gut mucosa by 12 hours postburn; restoration was evident by 48 hours after burn. ODC activity was increased in the proximal small bowel at 12 and 24 hours after burn in the rats in both the 20% burn and 60% burn groups; by contrast, only rats in the 60% burn group had increased ODC activity in the distal small bowel. ODC mRNA levels increased in the proximal gut mucosa as early as 3 hours after the burn and returned to control values after 24 hours. These data show that mucosal restoration begins soon after burn injury and that the induction of ODC mRNA and ODC activity are important events.     

Intestinal and hepatic response to combined partial hepatectomy and small bowel resection in mice

BACKGROUND: Both partial-hepatectomy (PHx) and massive small bowel resection (SBR) are strong mitogenic signals to the remnant liver and intestine, respectively. This study tested the hypothesis that PHx was an additive signal for intestinal adaptation after massive SBR. METHODS: Male mice underwent either sham SBR or 50% proximal SBR. Mice from these two groups were then subjected to a 70% PHx or sham PHx. After 3 days, parameters of intestinal adaptation and liver regeneration were recorded in the remnant intestine and liver, respectively. RESULTS: Intestinal adaptation following SBR occurred normally, but was not enhanced after concomitant PHx. On the other hand, SBR impaired the regenerative ability of the liver following PHx. CONCLUSIONS: Intestinal adaptation after SBR takes priority over liver regeneration after PHx. These data implicate a hierarchy with regard to adaptive alterations to organ loss and endorse an important role for the intestinal mucosa in the regulation of hepatic regeneration.     

Effect of luminal contents on postresectional longitudinal and mucosal growth in the ileum of suckling rats

Effects of luminal contents on adaptive growth of the ileum in the neonatal small bowel of rats were examined after resection of the proximal small bowel and after removal of the ileum from the enteric stream. Four weeks after resection of the proximal 60% of the small bowel in 10-day-old rats, the distal 40% of the small bowel elongated by 281%. This distal segment also elongated by 265% after intestinal transection (p greater than 0.05), but by only 191% when it was bypassed (bypass versus resection or transection, p less than 0.001). After resection the distal villi were 81% taller, but after transection they were only 19% taller (p less than 0.001 versus resection); after bypass they did not grow (p less than 0.001 versus resection or transection). The distal crypts were 404% deeper after resection, 331% deeper after transection (p less than 0.05), and 291% deeper after bypass (p less than 0.001 versus resection, p greater than 0.05 versus transection). The DNA content was 517% greater after resection, 364% greater after transection (p less than 0.001), and 73% greater after bypass (p less than 0.001 versus transection or resection). Maximal elongation of the small bowel occurs in the presence of luminal nutrition. Increasing luminal nutrition is associated with increasing mucosal hyperplasia.     

Influence of glutamine-supplemented parenteral nutrition on intestinal amino acid metabolism in rats after small bowel resection

Glutamine (Gln)-supplemented total parenteral nutrition (TPN) has been shown to improve mucosal adaptation after massive small bowel resection (SBR); however, its influences on intestinal amino acid metabolism remain unknown. In this study, intestinal amino acid flux, circulating plasma aminogram, mucosal glutaminase activity and protein, and DNA content were measured 7 days after massive SBR in rats receiving either standard (Std) or Gln-supplemented TPN. Sham-operated rats and rats fed chow after enterectomy served as controls. The uptake of Gln and the release of citrulline (Cit) by the remaining intestine was significantly decreased, with reduced mucosal glutaminase activity after SBR in the Chow and Std-TPN groups. Glutamine supplementation resulted in significantly increased gut Gln uptake compared with Std-TPN (P<0.01). Mucosal glutaminase activity, mucosal protein, and DNA content was also increased by Gln; however, the gut release of Cit remained unchanged (P>0.05). The subsequent decrease in circulating arginine (Arg) in the Gln-TPN group compared with the Std-TPN group (P<0.05) was attributed to an insufficient exogenous supply. These findings show that Gln-supplemented TPN improves mucosal growth and gut Gln uptake after SBR. However, the intestinal production of Cit, which remained low in both TPN groups, may lead to an insufficiency of endogenous Arg synthesis. Thus, both Gln and Arg may be essential amino acids after SBR.     

The effects of transections on the basic electrical rhythm in the canine jejunum.

The basic electrical rhythm (BER) was studied in situ in the jejunum in 14 anaesthetized mongrel dogs by the mean six monopolar electrodes. The BER frequency was measured in the intact intestine and after proximal and distal transections of the gut 5 cm apart from the electrodes. No significant differences were found between the BER frequencies recorded by each electrode, demonstrating the existence of a frequency plateau which remained after each transection. In the intact intestine the frequency in the plateau was 13.2 +/- 0.3 cpm2. After the proximal transection, this frequency dropped to 12.0 +/- 0.4 cpm (p less than 0.05) and, after the distal transection, it dropped to 10.9 +/- 0.4 cpm (p less than 0.005). This last frequency change shows the influence of the distal intestine on the electrical behaviour of the jejunum.     

烧伤早期家兔小肠细胞凋亡的研究

目的　探讨严重烧伤早期家兔小肠粘膜上皮细胞、淋巴细胞以及蚓状突淋巴细胞凋亡及其意义。　方法　采用日本大耳白兔 2 5只 ,随机分成 5组 :正常对照组、严重烧伤 3、6、12、2 4h组 ,每组均为 5只。各烧伤组制作成 30 %TBSAⅢ度烧伤动物模型 ,于伤后相应时相点对 5个部位的肠组织取材 ,行HE染色、电镜检查及用DNA切口末端标记技术 (TUNEL)行原位细胞凋亡检测 ,TUNEL切片作统计分析。　结果　HE染色烧伤组见较多凋亡细胞单个分散在小肠及蚓状突粘膜上皮层、粘膜固有层 (部分延伸到粘膜下层 )的淋巴小结和散在淋巴组织中 ;伤后 2 4h组有少数肠粘膜断裂 ;所有切片未见明显炎症及坏死现象。电镜显示凋亡小体形成。TUNEL法见大量呈蓝黑色的阳性细胞核 ,分布位置同HE染色。伤后 3h小肠及蚓状突细胞凋亡数较对照组已有明显增多 (P<0 .0 1) ,到 6和 12h显著升高达峰值 (P <0 .0 1) ,伤后 2 4h已下降接近 3h水平 ,但仍高于对照组 (P <0 .0 1) ;烧伤组家兔中段及远端小肠粘膜上皮细胞凋亡数均高于近端小肠 (P <0 .0 5 )。　结论　严重烧伤早期家兔小肠粘膜上皮细胞、淋巴细胞以及蚓状突淋巴细胞大量凋亡 ,中远端小肠粘膜上皮细胞凋亡较近端小肠显著 ,这些变化可能是烧伤后肠道细菌及内毒素移位的细胞学基础。     

Glucagon-like peptide 2 is a potent growth factor for small intestine and colon

Factors that stimulate gut mucosal proliferation may be beneficial during periods of gut disuse or atrophy. Recently glucagon-like peptide 2 (GLP-2) has been shown to stimulate small bowel growth. The purpose of our study was to compare the trophic effects of GLP-2 with those of neurotensin (NT), a potent gut trophic factor. Mice were randomized to receive either GLP-2, NT, or saline solution (control) for 10 days. The mice were killed on day 11, at which time the jejunum, ileum, and colon were removed, weighed, and DNA and protein content measured. Mice treated with GLP-2 showed a significant increase in the weight of the jejunum, ileum, and colon compared to both control and NT-treated mice. DNA content, a marker of cellular hyperplasia, was significantly increased in the small bowel and colon by treatment with GLP-2 and NT compared to control tissues. Small intestinal protein content, an indicator of cellular hypertrophy, was significantly increased by GLP-2 compared to both NT and control; protein content of the colon was greater in each of the treatment groups compared with control mice. We have demonstrated, for the first time, that GLP-2 stimulates colonic growth. In addition, GLP-2 is a potent trophic factor of normal small intestine with proliferative effects that are equal to or greater than those of NT Administration of GLP-2 may be useful clinically to enhance small intestinal regeneration and adaptation during periods of disease and in the early phases of the short bowel syndrome. Supported by grants from the National Institutes of Health (PO1 DK35608, ROl AG10885, and T32-DK07633). Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997, and published as an abstract in Gastroenterology 112:A1455, 1997.     

Hyperplasia and neoplasia of the intestinal tract.

Measurements of RNA and DNA in the rat have been used to identify mucosal hyperplasia in the remaining gut within 48 h of partial intestinal loss. Structural adaptation of the ileum is still present 3 months after jejunal resection, whereas transection of the bowel produces merely transient hyperplasia. A humoral factor can be transmitted between rats linked in vascular parabiosis that is capable of stimulating intestinal cell proliferation. Humoral agents may also explain reduced adaptation of the distal bowel after jejunal bypass as opposed to equivalent resection. Although bile can initiate prompt ileal hyperplasia, the additional presence of pancreatic juice is needed to prolong this effect. Adaptation is controlled by luminal and systemic factors that are closely interlinked. Experimental intestinal carcinogenesis is promoted by proximal enterectomy.     

The effect of intestinal anastomosis on gut growth and maturation

We evaluated the effect of intestinal anastomosis without resection on gut morphometry (muscle thickness, villus height, and crypt depth), growth indices (DNA, protein, and protein:DNA ratio), and disaccharidase activity (maltase, sucrase, and lactase) in the growing animal. A group of 10 weanling Sprague-Dawley rats at 21 days of age was subjected to intestinal transection and anastomosis in the upper jejunum, 10 cm distal to the ligament of Treitz. A second group of 10 similar rats was used as a control group. All rats were fed a regular diet and kept under the same conditions. They were sacrificed 2 weeks later. Body weight, intestinal weight, and intestinal length measurements were obtained. The intestine was divided into two sections: preanastomotic (section A) and postanastomotic (section B) in the surgery group and equivalent sections A and B in the control group. Specimens were subjected to morphometric evaluation and mucosal scrapings for biochemical analysis. Despite significant weight gain in the control group, there were no differences in intestinal length, intestinal weight, and mucosal weight between the two groups. Muscle thickness, villus height, and crypt depth were significantly increased in the preanastomotic segment. Protein and DNA were also higher in the preanastomotic segment, but the protein:DNA ratio was less affected. There was significantly decreased enzymatic activity in the preanastomotic segment. Intestinal anastomosis has a significant effect on gut growth and maturation in the growing animal and may have important implications in the postoperative management of newborns and infants following intestinal surgery.     

Enterotrophic effects of glucagon-like peptide 2 are enhanced by neurotensin

Combination therapy with enterotrophic agents may be useful in patients with the short bowel syndrome. The gut hormones neurotensin (NT) and glucagon-hke peptide 2 (GLP-2) are potent enterotrophic fattors when administered alone; however, their combined effects are not known. Using a GLP-2-producing tumor (STC-1), we determined whether administration of NT enhances the effect of GLP-2 on intestinal growth. Athymic mice were injected with STC-1 cells (6 × 10⁶) subcutaneously. Twenty-three days after STC-1 implantation, mice received either NT (300 μg/kg or 600 μg/kg) or saline solution (control) subcutaneously three times a day for 6 days. Two groups of tumor-free mice received either saline or NT for 6 days. At sacrifice, jejunum and ileum were collected, weighed, and analyzed for DNA and protein content. In the jejunum, NT combined with GLP-2 (from STC-1) increased weight, protein content (markers of mucosal hypertrophy), and DNA content (a marker of mucosal hyperplasia), compared to either NT or GLP-2 alone. In the ileum, the combination of NT and GLP-2 significantly increased weight and/or protein content compared to NT or GLP-2 alone. Administration of NT enhances the enterotrophic effects of GLP-2, augmenting hypertrophy of the entire small bowel and hyperplasia of the jejunum. The combination of NT and GLP-2 may be useful to enhance intestinal growth in patients with the short bowel syndrome. Supported in part by National Institutes of Health grants PO1 DK356O8, ROI DK48345, ROI AG10885, and T32 DK07633. Presented in part at the Surgical Forum of the American College of Surgeons, Chicago, Ill., October 12–17, 1997; and at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998.     

Role of bombesin on gut mucosal growth.

OBJECTIVE: The authors examined the effects of exogenous bombesin (BBS) on gut mucosal growth in chow-fed rats and the mucosal regeneration after gut atrophy brought about by feeding an elemental diet and after intestinal injury produced by methotrexate (MTX). SUMMARY BACKGROUND DATA: Bombesin is one of many gastrointestinal peptides implicated in the regulation of gut mucosal growth. Although BBS is known to stimulate growth of normal pancreatic tissue, the trophic effect of BBS on gut mucosa is less clear and its exact role in gut mucosal regeneration and repair is not known. METHODS: Rats were fed a regular chow diet (control) or an elemental diet plus either saline or BBS (10 micrograms/kg). In another experiment, rats fed a chow diet and treated with saline or BBS were given MTX (20 micrograms/kg) or a single intraperitoneal injection. In all experiments, small and large bowel mucosa and pancreas were removed and analyzed for BBS-mediated proliferation. RESULTS: Bombesin produced significant mucosal proliferation of the small bowel at day 14, but not at day 7, in rats fed regular chow. In contrast, BBS treatment for 7 days produced significant proliferation in both the atrophic and injured gut mucosa of rats given elemental diet or MTX. CONCLUSIONS: Bombesin may be an important enterotrophic factor for normal mucosal proliferation and may be clinically beneficial as an agent to restore or maintain gut mucosa during periods of atrophy or injury.     

Effect of growth hormone, epidermal growth factor, and insulin on bacterial translocation in experimental short bowel syndrome

BACKGROUND/PURPOSE: An adaptive process starts in the remaining intestine after massive resection, and several trophic factors including growth hormone (GH), epidermal growth factor (EGF), and insulin (INS) have been shown to have a positive effect on it. Bacterial translocation (BT) is frequent after extensive small bowel resection, but the effects of GH, EGF, or INS have not been investigated in experimental short bowel syndrome (SBS). This study tests the hypothesis that GH, EGF, or INS decrease BT in SBS in rats with parenteral nutrition (PN). METHODS: Thirty-eight adult Wistar rats underwent central venous cannulation and were assigned randomly to 1 of 4 groups receiving for 10 days 4 treatment regimes: (1) PN group (n = 10): fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve; (2) GH group (n = 9): fasting, same PN regime and resection, GH (1 mg/kg/d, subcutaneously); (3) EGF group (n = 9): fasting, PN, resection, EGF (150 microg/24 h intravenously); (4) INS group (n = 9): fasting, PN, resection, INS (1 UI/100 g/24 h subcutaneously). At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood samples were recovered and cultured. Several fragments of intestine were taken to determine cell proliferation (PCNA index) and morphometric parameters (villous height, crypt depth). RESULTS: GH, EGF, and INS groups showed a 28%, 29%, and 30% increase in gut mucosal thickness, and PCNA index rose 21%, 20%, and 25%, respectively in comparison with PN controls. Bacterial translocation to peripheral blood was detected in 0% of PN animals and in 44%, 40%, and 28% of GH, EGF, or INS rats, respectively (P < .05). No differences were found in BT in MLN or portal blood among groups. CONCLUSION: Administration of GH, EGF, or INS improves gut mucosal structure in rats with SBS under PN, but, surprisingly, the incidence of BT detected in peripheral blood was increased rather than decreased in animals receiving these treatments.