Progress in intestinal adaptation after enterectomy / 中华胃肠外科杂志

Intestinal adaptation is a spontaneous compensation of the remanent bowel after extensive enterectomy, which improves the absorption capacity of the remanent bowel to energy, fluid and other nutrients. Intestinal adaptation mainly occurs within 2 years after enterectomy, including morphological changes, hyperfunction and hyperphagia. Intestinal adaptation is the key factor for patients with short bowel syndrome to weaning off parenteral nutrition dependence and mainly influenced by length of remanent bowel, type of surgery and colon continuity. In addition, multiple factors including enteral feeding, glucagon-like peptide 2 (GLP-2), growth hormone, gut microbiota and its metabolites regulate intestinal adaptation via multi-biological pathways, such as proliferation and differentiation of stem cell, apoptosis, angiogenesis, nutrients transport related protein expression, gut endocrine etc. Phase III clinical trials have verified the safety and efficacy of teduglutide (long-acting GLP-2) and somatropin (recombinant human growth hormone) in improving intestinal adaptation, and both have been approved for clinical use. We aim to review the current knowledge about characteristics, mechanism, evaluation methods, key factors, clinical strategies of intestinal adaptation.

Rehabilitación del intestino utilizando un análogo semisintético del péptido 2 similar al glucagón. Primera experiencia con teduglutide en Uruguay / Intestinal rehabilitation using semisynthetic glucagon-like peptide-2 analogue. First experience with teduglutide in Uruguay / Reabilitação do intestino usando um análogo semi-sintético do peptídeo 2 semelhante ao glucagon. Primeira experiência com teduglutide no Uruguai

Resumen: La falla intestinal crónica (FIC) o tipo III es una condición invalidante, y la nutrición parenteral crónica (NPC) domiciliaria es el tratamiento que permite a estos pacientes mantenerse con vida. Sin embargo, solamente uno de cada tres países latinoamericanos cuentan con ese recurso, y sus complicaciones no son infrecuentes. Estas complicaciones son las principales indicaciones para trasplante intestinal, un procedimiento que en la mayoría de los países de ingresos medios no se ha desarrollado y no ha presentado los resultados esperados. En los últimos años, la rehabilitación intestinal a nivel mundial ha mejorado sustancialmente con el uso de análogos semisintéticos del péptido 2 similares al glucagón, existiendo cada vez mayor evidencia que demuestra la posibilidad de rehabilitación intestinal e independencia de la NPC con este fármaco, incluso en pacientes con anatomía desfavorable. Estos resultados han permitido mejorar la supervivencia y la calidad de vida de pacientes con FIC y, en muchas ocasiones, prescindir del trasplante. El paciente del caso que presentamos es el primero en recibir esta terapéutica en nuestro país. En este artículo analizamos la respuesta precoz favorable al tratamiento y sus perspectivas a futuro.

Abstract: Long-term home parenteral nutrition (HPN) is a life-saving treatment for patients with chronic intestinal failure, an invalidating condition. However, only 1 out of 3 countries can rely on this treatment and complications associated to chronic parenteral nutrition are rather frequent. The latter constitute the main indication for intestinal transplantion, a procedure that in most middle-income countries has not yet developed and has not shown the expected outcome. In recent years, intestinal rehabilitation has significantly improved at the global level with the use of GLP2, based on the growing evidence that proves the possibility of intestinal rehabilitation and independence from parenteral nutrition with Teduglutide, even in the case of patients with unfavorable anatomy. These results have caused a positive impact on survival and the quality of life of patients with chronic renal failure, and they can often abstain from transplant. The patient of the case study is the first one who received this therapy in our country and this article analyses his favorable early response to treatment and future perspectives.

Resumo: A insuficiência intestinal crônica (CIF) ou tipo III é uma condição incapacitante e a nutrição parenteral crônica (NPC) domiciliar é o tratamento que permite a sobrevida desses pacientes. No entanto, apenas 1 em cada 3 países latino-americanos dispõe desse recurso e as complicações da NPC não são raras. Essas complicações são as principais indicações para o transplante intestinal, procedimento que na maioria dos países de renda média não foi desenvolvido ou não apresentou os resultados esperados. Nos últimos anos, a reabilitação intestinal em todo o mundo tem melhorado substancialmente com o uso de sGLP2, com um número cada vez maior de evidências que mostram a possibilidade de reabilitação intestinal e independência da NPC, mesmo em pacientes com anatomia desfavorável. Esses resultados têm possibilitado prolongar a sobrevida e melhorar a qualidade de vida dos pacientes com CIF e, em muitos casos, dispensar o transplante. O paciente do caso que apresentamos é o primeiro a receber essa terapia em nosso país. Neste artigo, analisamos a resposta favorável ao tratamento precoce e suas perspectivas futuras.

Comparação dos níveis de proteína C reativa, GLP-1 e GLP-2 entre indivíduos diabéticos, obesos mórbidos e controles saudáveis: um estudo exploratório / Comparison of the levels of c-reactive protein, glp-1 and glp-2 among individuals with diabetes, morbid obesity and healthy controls: an exploratory study

ABSTRACT BACKGROUND: The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation. OBJECTIVE: To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls. METHODS: An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP. RESULTS: There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively). CONCLUSION: GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.

RESUMO CONTEXTO: Os peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2) são hormônios gastrointestinais que podem afetar diretamente a homeostase glicêmica; a atividade de ambos parece ser significativamente afetada pela inflamação crônica. OBJETIVO: Avaliar os níveis pós-prandiais dos peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2), proteína C reativa (PCR) e as curvas pós-prandiais de glucose e insulina entre indivíduos com obesidade, diabetes tipo 2 e controles saudáveis. MÉTODOS: Estudo piloto transversal, que envolveu indivíduos aguardando a realização de cirurgia bariátrica/metabólica e controles saudáveis. Os níveis de GLP-1, GLP-2, glucose e insulina foram obtidos após um teste de refeição padrão. A inflamação foi avaliada através dos níveis de PCR. RESULTADOS: Houve 30 indivíduos avaliados no estudo, divididos em três grupos: obesos mórbidos sem diabetes (NDO; n=11 pacientes), diabéticos com obesidade leve (T2D; n=12 pacientes) e controles (C; n=7 pacientes). Os níveis médios de PCR foram significativamente maiores no grupo NDO (6,6±4,7 mg/dL) do que nos grupos T2D (3,3±2,2 mg/dL) e C (2,5±3,2 mg/ dL) (P=0,038). Os níveis de GLP-1 após o teste de refeição padrão e a área sob a curva do GLP-1 não diferiram significativamente entre os grupos. Os níveis de GLP-2 foram significativamente mais baixos nos grupos NDO e T2D do que no grupo C em todos os tempos avaliados. A área sob a curva do GLP-2 foi significativamente menor nos grupos NDO e T2D do que no grupo C (P=0,05 and P=0,01, respectivamente). CONCLUSÃO: Os níveis de GLP-2 encontram-se alterados em indivíduos com obesidade e diabetes. Este mecanismo parece estar envolvido na prevenção da piora da homeostase glicêmica nestes indivíduos.

Research advances in association between childhood obesity and gut microbiota / 中国当代儿科杂志

In recent years, more and more studies have noted the close association between gut microbiota and the development and progression of obesity. Gut microbiota may act on obesity by increasing energy intake, affecting the secretion of intestinal hormones, inducing chronic systemic inflammation, and producing insulin resistance. This article reviews the association between childhood obesity and gut microbiota, as well as possible mechanisms, in an attempt to provide a reference for the etiology, prevention and treatment of childhood obesity.

GLP-2: a poorly understood mediator enrolled in various bariatric/metabolic surgery-related pathophysiologic mechanisms / GLP-2: um mediador pouco compreendido envolvido em diversos mecanismos fisiopatológicos relacionados à cirurgia bariátrica/metabólica

ABSTRACT Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. Method s: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected. Results: There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss. Conclusion: GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques.

RESUMO Introdução: O peptídeo semelhante ao glucagon-2 (GLP-2) é hormônio gastrointestinal com efeitos predominantemente tróficos sobre a mucosa intestinal. Objetivo: Avaliar criticamente a literatura atual a respeito da cirurgia bariátrica/metabólica sobre os níveis de GLP-2 e suas potenciais implicações clínicas. Métodos: Revisão narrativa realizada através de pesquisa on-line nas bases de dados Medline e LILACS. Foram selecionados seis estudos prospectivos em humanos, dois transversais em humanos e três experimentais em animais. Resultados: Existem evidências demonstrando aumento significativo nos níveis de GLP-2 após o bypass gástrico, a operação de Scopinaro e a gastrectomia vertical. Não foram observadas diferenças entre o bypass gástrico e a gastrectomia vertical em relação ao aumento do GLP-2. Não há correlação entre os níveis de GLP-2 e a ocorrência de perda de peso pós-operatória adequada ou insuficiente. Conclusão: O GLP-2 desempenha importantes papel sobre a regulação da absorção de nutrientes, permeabilidade da mucosa intestinal, controle da reabsorção óssea e regulação da saciedade. O impacto combinado destes efeitos potencialmente exerce efeito adaptativo ou compensatório importante no contexto das diferentes técnicas bariátricas.

Correlation between pre and postoperative levels of glp-1/glp-2 and weight loss after roux-en-y gastric bypass: a prospective study / Correlação entre os níveis pré e pós-operatórios de glp-1/glp-2 e a perda de peso após o bypass gástrico em y-de-roux: um estudo prospectivo

ABSTRACT Background: The role of gut hormones in glucose homeostasis and weight loss achievement and maintenance after bariatric surgery appears to be a key point in the understanding of the beneficial effects observed following these procedures. Aim: To determine whether there is a correlation between the pre and postoperative levels of both GLP-1 and GLP-2 and the excess weight loss after Roux-en-Y gastric bypass (RYGB). Methods: An exploratory prospective study which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 after standard meal tolerance test (MTT) were determined before and after surgery and then correlated with the percentage of excess loss (%EWL). Results: GLP-2 AUC presented a significant postoperative increase (945.3±449.1 vs.1787.9±602.7; p=0.0037); GLP-1 AUC presented a non-significant trend towards increase after RYGB (709.6±320.4 vs. 1026.5±714.3; p=0.3808). Mean %EWL was 66.7±12.2%. There was not any significant correlation between both the pre and postoperative GLP-1 AUCs and GLP-2 AUCs and the %EWL achieved after one year. Conclusion: There was no significant correlation between the pre and postoperative levels of the areas under the GLP-1 and GLP-2 curves with the percentage of weight loss reached after one year.

RESUMO Racional: O papel de hormônios gastrointestinais sobre a homeostase glicêmica e a obtenção e manutenção da perda de peso após a cirurgia bariátrica parece ser elemento fundamental na compreensão dos benefícios observados após estes procedimentos. Objetivo: Determinar se há correlação entre os níveis pré e pós-operatórios de GLP-1 e GLP-2 com a perda do excesso de peso após o bypass gástrico em Y-de-Roux. Métodos: Estudo prospectivo exploratório que envolveu 11 indivíduos submetidos ao bypass gástrico, acompanhados por 12 meses. Os níveis GLP-1 e GLP-2 após um teste de refeição padrão foram determinados antes e 12 meses após a operação e então foram correlacionados com o percentual de perda do excesso de peso. Resultados: Houve aumento significativo da área sob a curva do GLP-2 após a operação (945,3±449,1 vs. 1787,9±602,7; p=0,0037); a área sob a curva do GLP-1 apresentou tendência não-significativa à elevação após o procedimento (709,6±320,4 vs. 1026,5±714,3; p=0,3808). O percentual médio de perda de peso foi 66,7±12,2%. Conclusão: Não houve nenhuma correlação significativa entre os níveis pré e pós-operatórios das áreas sob as curvas de GLP-1 e GLP-2 com o percentual de perda de peso atingido após um ano.

The protective effect of recombinant glucagons like peptide-2 on intestinal mucosa of burn rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the protective effect of recombinant glucagons like peptide-2 (GLP-2) on intestinal mucosa of rats with severe burns.</p><p><b>METHODS</b>SD rats of either sex were randomly divided into 4 groups: normal control (N, n = 6), burn control group (C, n = 6), recombinant GLP-2 group (Gr, n = 6, with subcutaneous injection of 100 nmol x kg(-1) x d(-1) recombinant GLP-2 at 4 post-burn hours (PBH) and synthesized GLP-2 group (G, n = 6, with subcutaneous injection of 100 nmol x kg(-1) x d(-1) synthesized GLP-2 at 4 PBH). Except the normal control group, all animals in the other groups received a 30% TBSA third degree burns, the rats were sacrificed on 7 postburn days (PBD) and the following indexes were determined: pathological examination of intestinal mucosa, mucosa permeability of intestinal mucosa, the ratio of mucosa wet weight and bowel mass or carcase weight, and the protein content of intestinal mucosa.</p><p><b>RESULTS</b>Compared with that in burn group [(0.350 +/- 0.040) mg/ml], the mucosa permeability significantly decreased in Gr (0.250 +/- 0.026) mg/ml and G (0.243 +/- 0.008) mg/ml groups, while the ratio of mucosa wet weight and carcase weight, the protein content of intestinal mucosa were significantly increased. In addition, the content of intestinal mucosal protein in Gr group [(57.9 +/- 2.8) mg/g wet weight] was higher than that in G group [(48.9 +/- 4.1) mg/g wet weight]. In contrast to normal controls, the villi of intestinal mucosa in rats on 7 PBD were obviously shortened and exfoliated, with deranged disposition and thinned basal membrane. No obvious difference of the injury was observed between Gr and G groups, and the injury was milder when compared with burn group.</p><p><b>CONCLUSION</b>Recombinant GLP-2, as well as synthesized GLP-2, exhibits obvious protective effect on intestinal mucosa in alleviating injury to intestinal mucosa in burn rats.</p>

Management of intestinal failure.

Intestinal failure (IF) occurs when the body is unable to sustain its energy and fluid requirements without support, due to loss of functional small bowel. Prolonged IF is seen after large intestinal resection and described as short bowel syndrome (SBS). The hallmark of the management is parental nutrition (PN), which is costly and may be associated with the well-recognized problems of parental nutrition associated liver disease (PNALD) and line related sepsis. Cessation of PN at the earliest possible stage is desirable but for this enteral autonomy has to be achieved first. Intestinal adaptation occurs when the remaining gut goes through morphological changes increasing its absorptive capacity. Factors such as intraluminal nutrients, gastrointestinal secretions and hormones facilitate adaptation. Enteral feeds are a potent stimulant to adaptation and should be started as soon as the clinical situation permits. Some drugs are thought to increase intestinal adaptation. These include glutamine, growth hormone and glucagon like peptide- 2, but there is a paucity of pediatric data to guide their use. In some cases surgical bowel lengthening procedures can be performed to increase the absorptive surface area. An isolated liver transplantation may be required if the liver has sustained irreversible damage but intestinal autonomy seems achievable. When prolonged PN is either unsustainable or associated with unacceptable side effects, small bowel transplantation should be considered as a treatment option.

Effect of glucagon-like peptide 2 on the intestinal mucosal immunity and correlative cytokines in mice with gut ischemia/reperfusion injury / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of glucagon- like peptide 2 on intestinal mucosa immunity after ischemia/reperfusion injury and explore the possible mechanisms.</p><p><b>METHODS</b>A total of 70 ICR mice were randomly divided into three groups including normal control group(N), I/R group(C) and GLP-2 treatment group(T) (treated with GLP-2,200 microg/kg). The mice were sacrificed on the 1st, 3rd and 5th day after I/R injury. Liver,spleen and mesenteric lymph nodes samples were collected for bacterial culture. The endotoxin levels in plasma were also measured. Small intestine washing were obtained for IgA and the intestine homogenized were analyzed for Th1/Th2 cytokines.</p><p><b>RESULTS</b>The rate of bacterial translocation and the level of endotoxin in group C were significant higher than those in group T and group N. The IgA level in the lavage of the intestine was significantly decreased on the 1st day after I/R in group C and T compared with that in group N, while there was no difference between group C and T. The IgA level increased on the 3rd day and returned to normal on the 5th day after I/R in group T, while that in group C was still lower than normal. In group C, the levels of Th1-type (IL-2 and IFN-gamma) cytokines increased, the levels of Th2-type (IL-4 and IL-10) decreased significantly on the 1st day and then increased gradually. The change pattern of cytokines levels in group T resembled that in group C, but the levels of IL-4 and IL-10 in group T returned to normal on the 5th day after I/R.</p><p><b>CONCLUSIONS</b>GLP-2 supplementation can partly protect the intestinal mucosal immunity. The mechanism may probably be related to the restitution of the balance of Th1/Th2 cytokines in the intestinal mucosa in mice.</p>

Transfection and identification of the cloned strain that stably expressing glucagon like peptide-2 receptor in CaCO2 cell lines / 中华烧伤杂志

<p><b>OBJECTIVE</b>To establish Caco2 cell line with stable expression of glucagon like peptide-2 receptor( GLP-2R) , in order to establish an in vitro model for the study of protective mechanism of GLP-2 of the intestinal tract.</p><p><b>METHODS</b>The GLP-2R/pcDNA3. 1 ( + ) plasmid was verified by restriction endonuclease and sequencing , and then it was transfected into Caco2 cells with lipofectamine. After G418 selection, the clones with stable expression of GLP-2R were obtained by limited dilution cloning and expanding. The mRNA and protein expression of GLP-2R in normal human intestine, Caco2 cells, HER293, VE cells, as well as in transfected Caco2 cells were determined with RT-PCR and Western blot.</p><p><b>RESULTS</b>The sequence of GLP-2R/pcDNA 3. 1 plasmid was correct. No expression of GLP-2R mRNA and protein was found in HER293 and VE cells, but weak expression were found in Caco2 cells, and strong expression was found in normal human intestines. The expression of GLP-2R mRNA and protein expression in Caco2/GLP-2R ( + ) cells were obviously increased after transfection.</p><p><b>CONCLUSION</b>GLP-2R has special distribution. The expression of GLP-2R is weak in normal Caco2 cells. The establishment of Caco2/GLP-2R ( + ) cellular model is beneficial for the further research of the mechanism of action of GLP-2.</p>

Effects of glucagon-like peptide 2 on the adaptation of residual small bowel in a rat model of short bowel syndrome / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of glucagon-like peptide 2 (GLP-2) on the morphology and functional adaptation of the residual small bowel in rat model of short bowel syndrome.</p><p><b>METHODS</b>Twenty rats with 75% of the midjejunoileum removed were randomly divided into two groups, and received intra-peritoneal injection of GLP-2(250 micro*gd*kg-1*d-1) or subcutaneous injection saline(0.5 ml, twice one day) after operation. On postoperative day 6, the morphological changes of the residual jejunum and ileum, the expression of proliferating cell nuclear antigen(PCNA), and the mRNA expressions of Na-D-glucose cotransporters (SGLT1) and peptide cotransporters (PEPT1) were determined. The intestinal glucose absorption data per unit length as well as per unit weight of ileum were measured by in vivo circulatory perfusion experiment.</p><p><b>RESULTS</b>The morphological parameters of the residual gut such as the thickness of mucosa, height of villus, depth of crypt, and PCNA positive index were significantly higher, while the apoptosis rate per unit of mucosal square was significantly lower in GLP-2 treatment group than those in the control group. The expressions of mRNA SGTLl and PEPT1 in the residual ileum were significantly higher than those in the control group. There was no significant difference in glucose absorption rate per gram of mucosal wet weight between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>GLP-2 could improve morphological and functional adaptation of the residual small bowel by stimulating enterocyte proliferation and decreasing enterocyte apoptosis in short bowel syndrome.</p>

Protective effects of glucagon-like peptide 2 on intestinal ischemia/reperfusion injury in mice / 中国应用生理学杂志

<p><b>AIM</b>To investigate the protective effects of glucagon-like peptide 2(GLP-2) on intestinal ischemia/reperfusion (I/R) injury in mice.</p><p><b>METHODS</b>Intestinal ischemia/reperfusion model in mice were set up and 32 mice of Kunming species were divided randomly into 4 groups (n=8): Sham group, I/R group, I/R + GLP-2 group and I/R + glutamine group. The morphologic changes of intestinal mucosa were observed under LM. The villus height and crypt depth of intestine, the activity of diamine oxidase (DAO) in intestine and bacterial translocation rates of mesenteric lymph nodes (MLN) were detected.</p><p><b>RESULTS</b>Compared with sham operation group, the intestinal villi were sloughed in I/R group with decreased villus height and crypt depth (P < 0.01), the DAO activities were decreased (P < 0.01), and MLN bacterial translocation rates were increased (P < 0.05). While GLP-2 administration improved the villus damage, increased DAO activity (P < 0.01), and decreased MLN bacterial translocation rates (P < 0.05), compared with I/R group.</p><p><b>CONCLUSION</b>GLP-2 have protective effects on intestinal morphology and barrier function after ischemia/reperfusion injury in mice.</p>

Influence of glucagon-like peptide-2 on the proliferation of the intestinal mucosal cells in scalded rats / 中华烧伤杂志

<p><b>OBJECTIVE</b>To explore the influence of glucagon-like peptide-2 (GLP-2) on the proliferation of the intestinal mucosal cells in scalded rats.</p><p><b>METHODS</b>Fifty-five Wistar rats were employed in the study and were randomly divided into normal control (C), simple scald (S) and scald with GLP-2 treatment (G) groups. The rats in G group received GLP-2 introperitoneally in a dose of 200 micro g/kg two times a day. The rats in S and G groups were sacrificed at 6 postburn hours (PBHs), 12 PBHs, 1 postburn day (PBD1), PBD3 and PBD5 and the rats in C group were also sacrificed. Plasma diamine oxidase (DAO) activity, cell cycle protein cyclin D expression and the proliferating cell nuclear antigen (PCNA) in all groups were determined. And the histological change in the intestinal mucosal tissue was observed simultaneously. with all the above determinations.</p><p><b>RESULTS</b>Compared with those in C group, the PCNA expression at 6 and 12 PBHs in S group was enhanced slightly and weakened at PBD1, reaching the lowest level at PBD3 and it was still lower than that in C group at PBD5. Changes in PCNA in G group were similar to that in S group, except that the expression at PBD3 and PBD5 was stronger than that in S group. The intestinal mucosal cyclin D protein expression was increased at 6 and 12 PBHs in S group, but decreased by 40% before injury at PBD1. Nevertheless, the cyclin D protein expression in G group was much higher than that in S group at PBD1, PBD3 and PBD5. The plasma DAO activity increased significantly in rats after burn injury. But the activity decreased obviously after GLP-2 treatment for 5 days (P < 0.01). It was observed histologically in G group that the lining of Exogenous intestinal villi was regular and well arranged without evident epithelial exfoliation.</p><p><b>CONCLUSION</b>Exogenous GLP-2 might ameliorate intestinal mucosal injury in scalded rats, and promotion of the expression of PCNA and cyclin D, resulting in proliferation of injured intestinal mucosal cells, might be the underlying mechanisms.</p>