Short Bowel Syndrome Rats Research Articles

Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat

Background/Purpose Because of their ability to inhibit intestinal bacterial overgrowth, probiotics (PROs) have been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of PROs on bacterial translocation and intestinal regrowth after massive small bowel resection in a rat. Methods Male Sprague-Dawley rats were divided into 3 experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent 75% small bowel resection, and SBS-PRO rats underwent bowel resection and were treated with a PRO given in drinking water from day 4 through 14. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, enterocyte proliferation and enterocyte apoptosis) and bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood, and peripheral blood were determined on day 15 after operation. Results Sham rats exhibited a 20% BT to the mesenteric lymph nodes (level I), liver (level II), and blood (level III). Short bowel syndrome rats demonstrated a 100% BT to lymph nodes (level I) and liver (level II) and 40% translocation to peripheral blood (level III). Treatment with PROs resulted in a significant decrease in BT to all 3 target organs and decreased enterocyte apoptosis compared with SBS-untreated animals. Short bowel syndrome rats showed a significant increase (vs sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. Short bowel syndrome rats also had a greater proliferation index and apoptotic index in both jejunum and ileum compared with sham animals. SBS-PRO rats showed a significant increase (vs SBS rats) in crypt depth in ileum and a mild decrease in apoptotic index in jejunum and ileum, compared with SBS-untreated animals. Conclusions In a rat model of SBS, PROs decrease BT through mechanisms which maybe dependent on intestinal mucosal integrity.

Two-hit rat model of short bowel syndrome and sepsis: independent of total parenteral nutrition, short bowel syndrome is proinflammatory and injurious to the liver

Introduction Infants with short bowel syndrome (SBS) are at a high risk for infectious complications and liver failure. We hypothesized that SBS, independent of total parenteral nutrition, is a proinflammatory state that is magnified by sepsis. Methods Sprague-Dawley rats were divided into 2 groups: sham laparotomy (SH, n = 10) or 75% small bowel resection (n = 10). After 14 days, each group underwent a second sham laparotomy (SH/SH and SBS/SH) or cecal ligation and puncture, followed 16 hours later by cecal excision and peritoneal washout (SH/sepsis and SBS/sepsis). Animals were killed 56 hours later. Results The SBS rats had higher serum levels of interleukin (IL) 6 vs SH (355 ± 99 vs 104 ± 71 pg/mL, P < .05). Liver injury scores were higher in SBS/sepsis compared with SBS/SH animals (3.7 ± 0.7 vs 1.9 ± 0.3, P < .05). Hepatic messenger RNA levels of IL-6 (12.8-fold change [FC]) and tumor necrosis factor α (5.65 FC) were elevated in SBS vs SH rats; and IL-6 (114 FC), tumor necrosis factor α (3.87 FC), and Toll-like receptor 4 (7.65 FC) were increased in SBS/sepsis compared with SH/sepsis animals. Conclusion Our results suggest that SBS, independent of total parenteral nutrition, is a proinflammatory state and that sepsis induces an exaggerated proinflammatory cytokine response that may play an important role in liver damage and may be mediated by Toll-like receptor 4.

Bombesin stimulates enterocyte turnover following massive small bowel resection in a rat

Recent evidence suggests that bombesin (BBS) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of BBS on enterocyte turnover after massive small bowel resection in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, short bowel syndrome (SBS) rats underwent a 75% small bowel resection, and SBS-BBS rats underwent bowel resection and were treated with BBS given subcutaneously at a dose of 20 mug/kg, once daily, from postoperative day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth), enterocyte proliferation and enterocyte apoptosis were determined in jejunum and ileum on day 15 following operation. RT-PCR technique was used to determine Bax and Bcl-2 gene expression in ileal mucosa. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Treatment with BBS resulted in a significant increase in ileal bowel and mucosal weight, ileal mucosal DNA and protein, jejunal and ileal villus height, jejunal crypt depth, and jejunal and ileal proliferation index compared to SBS-animals. SBS rats showed a significant increase in Bax and Bcl-2 expression in ileum that was accompanied by a significant increase in cell apoptosis compared to sham animals. SBS-BBS rats demonstrated a significant decrease in Bax and Bcl-2 expression in ileum and a decrease in apoptotic index compared to SBS-animals. In conclusion, in a rat model of SBS, BBS enhances enterocyte turnover and stimulates structural intestinal adaptation. Decreased Bax expression may be responsible for the inhibitory effect of BBS on enterocyte apoptosis.

Effect of Enteral Nutrition Formula on Fat Absorption and Serum Free Fatty Acid Profiles in Rat with Short‐Bowel Syndrome

AbstractThe effects of enteral nutrition containing long chain triglycerides (LCT) and medium chain triglycerides (MCT) or L‐arginine (Arg) on fat absorbability, serum free fatty acid profiles and intestinal morphology in rats with short‐bowel syndrome (SBS) were studied using gas chromatography. Twenty‐eight Sprague‐Dawley rats were randomly assigned to 4 groups:sham operation fed with LCT as control; 85% small bowel resection fed with LCT, MCT/LCT, and Arg/LCT, respectively. SBS rats showed a decrease of fat absorptivity. Enteral nutrition supplemented with MCT could increase fat absorptivity. L‐Arginine enhanced enteral nutrition was associated with the elevation of fat absorptivity, possibly due to its enterotrophic effect on remnant small bowel mucosa. LCT group showed a significant deficiency of total free fatty acid and the decreased essential fatty acid content, which was improved in other two SBS groups.

Oral Insulin Enhances Intestinal Regrowth Following Massive Small Bowel Resection in Rat

Experimental studies have suggested that insulin (INS) plays an important role in small intestinal growth and development. In the present study we investigated the effect of oral INS on structural intestinal adaptation and enterocyte proliferation and loss via apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-INS rats underwent bowel resection and were treated with oral INS given in the drinking water from the 3rd to the 15th postoperative day. Parameters of intestinal adaptation (bowel and mucosal weight, mucosal DNA and protein, villous height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. SBS-INS rats demonstrated a significant increase (vs SBS rats) in jejunal and ileal overall bowel and mucosal weight, ileal mucosal DNA and protein, ileal villous height, and crypt depth. SBS-INS rats also showed an increased cell proliferation index in jejunum and ileum and decreased apoptotic index in jejunum compared to SBS animals. In conclusion, in a rat model of SBS, oral INS strongly enhances intestinal adaptation. Possible mechanisms may include increased cell proliferation and decreased enterocyte loss via apoptosis.

Parenteral arginine impairs intestinal adaptation following massive small bowel resection in a rat model

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal structure and absorptive function. It is also well known that the route of administration modulates the effects of ARG. The present study evaluated the effects of parenteral ARG on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-ARG rats underwent a 75% small bowel resection and were treated with ARG given subcutaneously at a dose of 300 mug/kg, once daily, from days 3 to 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. The SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. The SBS-ARG animals demonstrated lower ileal bowel and mucosal weights, jejunal mucosal DNA and ileal mucosal protein, and jejunal and ileal villus height and crypt depth compared with SBS animals. The SBS-ARG rats also had a lower cell proliferation index in both jejunum and ileum and a greater enterocyte apoptotic index in ileum compared with the SBS-untreated group. In conclusion, in a rat model of SBS, parenteral arginine inhibits structural intestinal adaptation. Decreased cell proliferation and increased apoptosis are the main mechanisms responsible for decreased cell mass.

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.

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.

Effect of dietary fat on early morphological intestinal adaptation in a rat with short bowel syndrome.

Among factors promoting mucosal hyperplasia after bowel resection, long-chain fatty acids may have a special role. The purpose of the present study was to evaluate the effects of high-fat diet (HFD) on early intestinal adaptation in rats with short bowel syndrome (SBS). Male Sprague-Dawley rats underwent either a bowel transection with re-anastomosis (Sham rats) or 75% small bowel resection (SBS rats). Animals were randomly assigned to one of three groups: Sham rats fed normal chow (Sham-NC); SBS rats fed NC (SBS-NC); and SBS rats fed HFD (SBS-HFD). Rats were killed on days 3 or 14. Body weight and parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth) were determined at time of killing. By day 3, SBS-HFD rats demonstrated higher duodenal and jejunal bowel and mucosal weights and ileal villus height and jejunal crypt depth vs SBS-NC rats. By day 14 SBS-HFD rats continued to demonstrate increased duodenal and jejunal bowel weight and duodenal mucosal weight vs SBS-NC animals. We conclude that early exposure to HFD both augmented and accelerated structural bowel adaptation in a rat model of SBS.

Liposaccharide endotoxemia reduces cell proliferation and decreases enterocyte apoptosis during intestinal adaptation in a rat model of short-bowel syndrome

Sepsis is frequently associated with or com- plicates short-bowel syndrome (SBS). To investigate the effects of lipopolysaccharide (LPS) endotoxemia on en- terocyte proliferation and death via apoptosis in a rat model of SBS, adult male Sprague-Dawley rats were divided into three experimental groups: sham rats un- derwent bowel transection and reanastomosis; SBS rats underwent 75% small-bowel resection; and SBS-LPS rats underwent 75% bowel resection and were given intraperitoneal injections of LPS 10 mg/kg. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and death via apoptosis were determined on day 15 after the operation. Statis- tical analysis was determined by Student's and ANOVA tests with a P less than 0.05 considered significant. SBS- LPS animals demonstrated a significant decrease (vs SBS rats) in duodenal (20%), jejunal (30%), and ileal (15%) overall weight, duodenal (20%), jejunal (27%), and ileal (18%) mucosal weight, jejunal (20%) and ileal (30%) mucosal DNA, jejunal (29%) and ileal (31%) villus height, and jejunal (14%) and ileal (29%) crypt depth. LPS endotoxemia led to reduced cell proliferation and enterocyte apoptosis compared to untreated SBS ani- mals. Thus, in a rat model of SBS, LPS endotoxemia inhibits intestinal adaptation. A possible mechanism may be decreased cell proliferation. Decreased entero- cyte loss via apoptosis may reflect a reduced number of enterocytes. Other mechanisms (necrosis) may be mainly responsible for cell death following LPS injection.

Effect of a high fat diet on lipid absorption and fatty acid transport in a rat model of short bowel syndrome.

Long chain fatty acids (LCFAs) appear to be powerful stimulants for small bowel adaptation in patients with short bowel syndrome (SBS). However, the dietary lipid content may alter intestinal lipid transport. The aim of this study was to investigate the effects of a high fat diet (HFD) on in vivo lipid absorption and molecular and cellular mechanisms of LCFAs uptake by the remaining bowel. Male Sprague-Dawley rats (240-280) were randomly assigned to one of three groups: sham rats fed normal chow (sham-NC), SBS rats fed NC (SBS-NC) and SBS rats fed HFD (SBS-HFD). SBS rats underwent a 75% small bowel resection. Rats were sacrificed on day 3 or 14. Body weight, fat intake and fat clearance (total fecal fat) were measured twice a week. Fat absorbability was calculated as intake minus clearance and was expressed as percent of intake. Total RNA from the mucosa of duodenum, jejunum and ileum was extracted using TRIZOL Reagent. Northern blot analysis was performed to determine FAT/CD36 mRNA levels. Enterocyte LCFA transport was measured on day 14. LCFA uptake was determined by measuring cellular [3H]-oleate uptake over time (4-120 s). Mean (+/-SE) FAT/CD36 mRNA levels and oleate uptake kinetic parameters were analyzed using ANOVA. Fat absorbability diminished after bowel resection, suggesting fat malabsorption. Remaining bowel in SBS-NC rats responded by an increase in FAT/CD36 mRNA levels in the duodenum and ileum on day 3, and the duodenum and jejunum on day 14 compared to sham-NC animals, and was accompanied by an increase in enterocyte LCFA transport in all segments. Exposure to a HFD for 14 days resulted in significantly increased fat absorbability after 3 days compared to SBS-NC rats. However, FAT/CD36 mRNA levels (vs. SBS-NC) decreased in all segments on day 3. On day 14, FAT/CD36 mRNA levels were decreased in the duodenum and ileum and were accompanied by reduced oleate uptake by isolated enterocytes in the ileum (vs. SBS-NC). In a rat model of SBS, early high fat diet increased lipid absorptive capacity of the intestinal remnant as seen by increased fat absorbability. The main mechanisms of this effect may be an acceleration of structural intestinal adaptation resulting in an increased number of enterocytes. However, at molecular and cellular levels HFD decreased mucosal FAT/CD36 mRNA levels and oleic acid uptake by isolated enterocytes.

Endotoxemia inhibits intestinal adaptation in a rat model of short bowel syndrome.

Sepsis is commonly associated with or complicates short bowel syndrome (SBS). The purpose of the present study was to investigate the effects of endotoxemia on intestinal adaptation in a rat model of SBS. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, SBS rats underwent 75% small bowel resection, and SBS-LPS rats underwent bowel resection and were given lipopolysaccharide. Bowel weight, organ weights, and parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth) were determined on day 15 following operation. The results of this study demonstrate that SBS rats showed a significant increase (vs. Sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. SBS-LPS animals demonstrated lower (vs. SBS rats) final body weight (215 +/- 7 vs. 287 +/- 10 g, P < 0.05), overall weight in duodenum (98+/- 2 vs. 119 +/-5 mg/cm, P < 0.05) and jejunum (144 +/- 9 vs. 189 +/- 16 mg/cm, P < 0.05), mucosal weight in jejunum (54 +/- 5 vs. 69 +/- 5 mg/cm, P < 0.05) and ileum (31 +/- 2 vs. 37 +/- 3 mg/cm, P < 0.05), mucosal DNA in jejunum (89 +/- 11 vs. 120 +/- 11 microg/cm, P < 0.05) and ileum (46 +/- 6 vs. 61 +/- 4 microg/cm, P < 0.05), jejunal crypt depth (152 +/- 19 vs. 189 +/- 12 microm, P < 0.05), and ileal villus height (405 +/- 63 vs. 515 +/- 30 pm, P < 0.05). In addition, the SBS group had no late (second week) mortality, whereas the SBS-LPS group had an 17% late mortality rate. In conclusion, in a rat model of SBS-LPS, endotoxemia appears to inhibit structural intestinal adaptation and increase mortality.

Lipopolysaccharide endotoxemia reduces cell proliferation and decreases enterocyte apopotosis during intestinal adaptation in a rat model of short-bowel syndrome.

Sepsis is frequently associated with or complicates short-bowel syndrome (SBS). To investigate the effects of lipopolysaccharide (LPS) endotoxemia on enterocyte proliferation and death via apoptosis in a rat model of SBS, adult male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis; SBS rats underwent 75% small-bowel resection; and SBS-LPS rats underwent 75% bowel resection and were given intraperitoneal injections of LPS 10 mg/kg. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and death via apoptosis were determined on day 15 after the operation. Statistical analysis was determined by Student's and ANOVA tests with a P less than 0.05 considered significant. SBS-LPS animals demonstrated a significant decrease (vs SBS rats) in duodenal (20%), jejunal (30%), and ileal (15%) overall weight, duodenal (20%), jejunal (27%), and ileal (18%) mucosal weight, jejunal (20%) and ileal (30%) mucosal DNA, jejunal (29%) and ileal (31%) villus height, and jejunal (14%) and ileal (29%) crypt depth. LPS endotoxemia led to reduced cell proliferation and enterocyte apoptosis compared to untreated SBS animals. Thus, in a rat model of SBS, LPS endotoxemia inhibits intestinal adaptation. A possible mechanism may be decreased cell proliferation. Decreased enterocyte loss via apoptosis may reflect a reduced number of enterocytes. Other mechanisms (necrosis) may be mainly responsible for cell death following LPS injection.

Effect of bowel resection and high-fat diet on heart CD36/fatty-acid translocase expression in a rat model of short-bowel syndrome.

Long-chain fatty acids (LCFA) are the major energy substrates for the heart. In short-bowel syndrome (SBS), LCFA delivery to the myocardium decreases due to fat malabsorption. Fatty-acid translocase (FAT)/CD36 has recently been identified as a LCFA-binding protein in heart tissue. To determine the effects of bowel resection and a high-fat diet (HFD) on myocardial CD36 expression, male Sprague-Dawley rats were randomly assigned to one of three groups: sham rats fed normal chow (Sham-NC); SBS rats fed NC (SBS-NC), and SBS rats fed a HFD (SBS-HFD). Control rats underwent transection and anastomosis; SBS animals underwent 75% small-bowel resection. Rats were killed at 3 or 14 days. Total body weight, heart weight, heart-tissue total lipid, serum cholesterol, and triglycerides were determined at death. Total RNA from the myocardium was extracted using TRIZOL reagent. Northern-blot analysis was used to determine FAT/CD36 mRNA. Statistical significance was determined by Student's t-test with P values below 0.05 considered significant. SBS-NC and SBS-HFD rats had significantly lower body weights compared with Sham-NC animals. The heart weights and myocardial total lipid did not vary among experimental groups. Decreases in plasma triglycerides (38.2 +/- 3.8 vs 58.8 +/- 5.5 mg/dl, P < 0.05) and cholesterol (38.2 +/- 6.9 vs 55.3 +/- 8.2 mg/dl, P < 0.05) in SBS-NC compared to Sham-NC rats on day 3 was accompanied by a twofold increase ( P < 0.05) in myocardial CD36/FAT mRNA levels. Early exposure to HFD led to increased (vs SBS-NC) plasma cholesterol (82.9 +/- 5.7 vs 38.2 +/- 6.9 mg/dl, P < 0.05) and triglycerides (62.5 +/- 15.6 vs 38.2 +/- 3.8 mg/dl, P < 0.05), and a concomitant decrease in CD36/FAT mRNA levels (45.1 +/- 17.8 vs 86.6 +/- 15%, respectively, P < 0.05). Plasma lipid concentration and myocardial CD36/FAT mRNA levels on day 14 were not significantly different among the experimental groups. In this rat model of SBS, the heart thus reacts to decreased LCFA delivery by increased tissue CD36/FAT mRNA levels and, consequently, active LCFA uptake. A HFD increased plasma lipid concentrations and decreased CD36/FAT levels.

Sandostatin impairs postresection intestinal adaptation in a rat model of short bowel syndrome.

Because of its antisecretory properties, sandostatin has been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of sandostatin on structural intestinal adaptation, cell proliferation and apoptosis in a rat model of SBS. Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-sandostatin rats underwent bowel resection and were treated with sandostatin (SBS-SND). Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-SND animals demonstrated lower (vs SBS rats) duodenal and jejunal bowel weights, jejunal and ileal mucosal weight, jejunal and ileal mucosal DNA and protein, jejunal and ileal villus height, cell proliferation index in the ileum, and enterocyte apoptosis in jejunum and ileum. We conclude that in a rat model of SBS sandostatin decreases cell proliferation and inhibits structural intestinal adaptation.

Recombinant human growth hormone and glutamine synergistically improve the adaptation of the remnant small intestine in rats with short bowel syndrome

OBJECTIVE: To study the effects and the underlying mechanism of recombinant human growth hormone (rhGH) and glutamine (Gln) on the adaptation of the remnant small intestine in parenterally nourished, short bowel syndrome (SBS) rats. METHOD: Four parenteral nutrition (PN) treatment groups of SBS rats were randomly arranged in a 2 × 2 factorial design as follows: (i) STD (standard PN) group (–rhGH, –Gln); (ii) Gln group (–rhGH, +Gln); (iii) rhGH group (+rhGH, –Gln); and (iv) rhGH + Gln group (+rhGH, +Gln). Morphological changes of the intestinal mucosa were investigated and the expression of proliferating cell nuclear antigen (PCNA) and the occurrence of apoptosis were observed by immunohistochemical staining and terminal deoxynucleotidyl transfer‐mediated dUTP‐biotin nick end‐labeling (TUNEL) methods. The level of intestinal insulin‐like growth factor‐1 (IGF‐1) mRNA was determined by northern blotting. RESULTS: The mucosal thickness, villous height, crypt depth and villous surface area of the remnant small intestine in the rhGH + Gln group were increased significantly as compared with the other three experimental groups, and there were synergistic effects between rhGH and Gln (P &lt; 0.01). The expression of PCNA was higher in the rhGH + Gln group than in the rhGH, Gln and STD groups (24.95 ± 3.93 vs 19.28 ± 3.25, 17.27 ± 3.38, and 8.37 ± 2.23 positive cells per crypt of Lieberkuhn, respectively; P &lt; 0.01) but the rate of apoptosis was lower in the rhGH + Gln group than in the rhGH, Gln and STD groups (5.68 ± 2.07 vs 8.06 ± 2.33, 10.00 ± 2.24 and 22.32 ± 3.84 positive cells per 100 cells, respectively; P &lt; 0.01). The intestinal IGF‐1 mRNA was also expressed at a higher level in the rhGH + Gln group than in the rhGH, Gln and STD groups (0.73 ± 0.05 vs 0.62 ± 0.04 vs 0.51 ± 0.04 and 0.41 ± 0.22, respectively; P &lt; 0.05). CONCLUSION: The synergistic combination of rhGH and Gln can significantly improve the adaptation of the remnant small intestine in parenterally fed SBS rats. An increase in cell proliferation and a decrease in cell apoptosis are both responsible for the intestinal adaptation. An increase in local IGF‐1 plays an important role in this process.

Effect of low fat diet on lipid absorption and fatty-acid transport following bowel resection.

Low-fat diets (LFD) are used extensively in many different clinical conditions. However, the effect of this diet on lipid absorption and cellular long-chain fatty-acid (LCFA) transport is unknown. Fatty-acid translocase (FAT), the rat homologue of human CD36, is one of several LCFA plasma-membrane transport proteins that may play an important role in intestinal lipid uptake. The purpose of this study was to investigate the effects of a LFD on intestinal expression of FAT/CD36, enterocyte fatty-acid transport, and in-vivo lipid absorption in rats following bowel resection. Adult male Sprague-Dawley rats were divided into five experimental groups: normal rats fed normal chow(NR-NC) (10 kcal% fat), normal rats fed a LFD (NR-LFD) (3 kcal% fat), sham rats fed normal chow (Sham-NC), short-bowel syndrome rats fed normal chow (SBS-NC), and SBS rats fed a LFD (SBS-LFD). SBS rats underwent 75% small-bowel resection, while sham animals underwent bowel transection and reanastomosis. Food intake, fecal mass, and fecal fat were measured over the last 3 days before death on day 14. Final body weight, plasma lipids and protein, and tissue total lipids in liver, adipose tissue, and intestine were determined at death. Total RNA from the mucosa of the duodenum, jejunum, and ileum was extracted for Northern blot analysis to determine fatty-acid translocase (FAT)/CD36 mRNA levels. An established cellular LCFA transport assay was used to determine isolated enterocyte [3H]-oleate uptake. Students t-test was used to determine statistical significance (P < 0.05). NR-LFD rats demonstrated a small increase in overall food absorption and no change in fat absorption compared to NR-NC animals. A significant decrease in FAT/CD36 mRNA levels was seen in the duodenum and jejunum in NF-LFD rats (vs NR-NC) and was accompanied by reduced LCFA transport by isolated enterocytes from the jejunum and ileum. SBS-LFD rats demonstrated decreased FAT/CD36 mRNA levels in all three segments and a concomitant decrease in LCFA uptake enterocytes compared to the SBS-NC group. In addition, SBS-LFD rats showed significantly lower final body weight and plasma lipids compared to SBS-NC animals.