Emodin alleviates intestinal mucosal injury in rats with severe acute pancreatitis via the caspase-1 inhibition.

BACKGROUND: Emodin, a traditional Chinese medicine, has a therapeutic effect on severe acute pancreatitis (SAP), whereas the underlying mechanism is still unclear. Studies showed that the intestinal mucosa impairment, and subsequent release of endotoxin and proinflammatory cytokines such as IL-1ß, which further leads to the dysfunction of multiple organs, is the potentially lethal mechanism of SAP. Caspase-1, an IL-1ß-converting enzyme, plays an important role in this cytokine cascade process. Investigation of the effect of emodin on regulating the caspase-1 expression and the release proinflammatory cytokines will help to reveal mechanism of emodin in treating SAP. METHODS: Eighty Sprague-Dawley rats were randomly divided into four groups (n=20 each group): SAP, sham-operated (SO), emodin-treated (EM) and caspase-1 inhibitor-treated (ICE-I) groups. SAP was induced by retrograde infusion of 3.5% sodium taurocholate into the pancreatic duct. Emodin and caspase-1 inhibitor were given 30 minutes before and 12 hours after SAP induction. Serum levels of IL-1ß, IL-18 and endotoxin, histopathological alteration of pancreas tissues, intestinal mucosa, and the intestinal caspase-1 mRNA and protein expressions were assessed 24 hours after SAP induction. RESULTS: Rats in the SAP group had higher serum levels of IL-1ß and IL-18 (P<0.05), pancreatic and gut pathological scores (P<0.05), and caspase-1 mRNA and protein expressions (P<0.05) compared with the SO group. Compared with the SAP group, rats in the EM and ICE-I groups had lower IL-1ß and IL-18 levels (P<0.05), lower pancreatic and gut pathological scores (P<0.05), and decreased expression of intestine caspase-1 mRNA (P<0.05). Ultrastructural analysis by transmission electron microscopy found that rats in the SAP group had vaguer epithelial junctions, more disappeared intercellular joints, and more damaged intracellular organelles compared with those in the SO group or the EM and ICE-I groups. CONCLUSIONS: Emodin alleviated pancreatic and intestinal mucosa injury in experimental SAP. Its mechanism may partly be mediated by the inhibition of caspase-1 and its downstream inflammatory cytokines, including IL-1ß and IL-18. Our animal data may be applicable in clinical practice.

Establishment of the critical period of severe acute pancreatitis-associated lung injury.

BACKGROUND: Since respiratory dysfunction is the main cause of death in patients with severe acute pancreatitis (SAP), elucidating the critical period of acute pancreatitis-associated lung injury (APALI) is of important clinical value. This study aimed to define the risk period of APALI by a series of studies including a dynamic analysis of total water content, ultrastructure and number of type II alveolar epithelial cells, and reactive oxygen metabolites (ROMs) of lung tissue in a mouse model of SAP, and a clinical analysis of APALI patients. METHODS: ICR mice were selected to establish a SAP model. They were given 7 intraperitoneal injections of cerulein (50 microg/kg body weight) at hourly intervals, followed by an intraperitoneal injection of lipopolysaccharide (15 mg/kg body weight). The total water content, ultrastructure, and number of type II alveolar epithelial cells, and ROMs of lung tissue were assessed before (0 hour) and after the establishment of SAP model (6 hours, 12 hours, 1 day, 4 days, and 7 days). In addition, we analyzed the data from 215 patients with APALI (PaO(2) <60 mmHg) treated at our hospital between January 1998 and December 2006. Statistical analyses were made using the F test. P values less than 0.05 were regarded as statistically significant. RESULTS: The total water content and ultrastructure of type II alveolar epithelial cells (mitochondria and lamellar bodies) of the lung in the SAP mice were significantly altered at 12 hours after the establishment of SAP model, and reached a maximum at 1 to 4 days. The number of type II alveolar epithelial cells and ROMs increased maximally at 1 day after the establishment of the model. Furthermore, clinical results showed that lung injury occurred at a mean of 3.1435+/-1.0199 days in patients with SAP. These clinical data were almost consistent with the results of the SAP model. CONCLUSION: The risk period for APALI is between the first and fourth day during the course of SAP.

[Effects of emodin on cell apoptosis of intestinal mucosa and serum leptin in rats with severe acute pancreatitis].

OBJECTIVE: To explore the mechanisms of emodin in protecting intestinal mucosal barrier in rat with severe acute pancreatitis (SAP). METHODS: Sixty SD rats were randomly divided into three groups: sham-operation group, untreated group, and emodin group. SAP in rats of the untreated group and the emodin group was induced by retrograde pumping of 3.0% sodium cholate to the common bile duct. Specimens were obtained 24 hours after the severe acute pancreatitis was induced. Serum level of leptin, serum activity of amylase and plasma content of endotoxin were measured. Ileum mucosa from ileocecal junction was observed by light microscopy and electron microscopy to measure pathological and ultrastructural changes. Apoptosis of ileum mucosal cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method, and expression of Bax in ileum mucosal cells was measured by immunohistochemical method. RESULTS: Compared with the sham-operation group, there was significant increase in the levels of leptin, endotoxin, the activity of amylase, apoptosis index and Bax expression in the untreated group (P<0.01). Compared with the untreated group, the level of endotoxin, apoptotic index and Bax expression level in the emodin group were significantly reduced (P<0.01) and the leptin level was increased (P<0.05). More severe pathological changes appeared in the untreated group than in the sham-operation group under the light and electron microscopes; meanwhile less severe damage was observed in the emodin group as compared with the untreated group. CONCLUSION: Emodin can inhibit the apoptosis of intestinal mucosa cells and up-regulate the serum leptin content to protect the intestina1 barrier function and prevent the translocation of bacteria and endotoxin.

Clinicopathological characteristics of gastrointestinal mesenchymal tumors and diagnostic value of endoscopic ultrasonography.

BACKGROUND AND AIM: Gastrointestinal mesenchymal tumors (GIMTs) are tumors which arise from mesenchymal cells other than lymphocytes or epithelial cells and include gastrointestinal stromal tumors (GISTs), smooth muscle tumors, neurogenic tumors, fibroblast tumors, and liparomphalus. Here, we studied the clinicopathologic characteristics of GIMTs and determined the diagnostic value of endoscopic ultrasonography (EUS) in GIMTs. METHODS: The morphological characteristics of 415 GIMT cases were observed using light microscopy. The expression of CD117, CD34, smooth muscle actin (SMA), S-100, and Ki-67 were detected using immunohistochemistry. EUS results were retrospectively analyzed in 76 cases. RESULTS: Among the 415 GIMT cases, there were 229 GIST cases, 178 smooth muscle tumor cases, and eight neurogenic tumor cases. Diffuse strong expression of CD117 was observed in 202 (88.2%) GISTs and strong expression of CD34 was observed in 135 (59.0%) GISTs. SMA and S-100 expression was detected in smooth muscle tumors (leiomyomas/leiomyosarcoma) and neurogenic tumors, respectively. Of the 12 cases with GISTs, nine cases with positive ki-67 expression and accompanied with more mitosis were pathologically diagnosed as malignant GISTs. Most of the borderline and malignant tumors were found in male patients. EUS was 98.7% accurate in determining GIMT locations, 82.9% accurate in diagnosing GIMTs, and 80.3% accurate in differentiating benign from malignant tumors. CONCLUSIONS: GISTs, rather than leiomyomas, are the most common GIMTs. Immunohistochemical markers, such as CD117, CD34, SMA, and S-100, can differentiate GISTs from smooth muscle and neurogenic tumors. The expression of Ki-67 in patients with significant karyokinesis supports a malignant tumor diagnosis. EUS is an accurate method for detecting GIMTs and differentiating between benign and malignant tumors. Use of endoscopic ultrasound-guided fine-needle aspiration biopsies may enable clinicians to make more accurate diagnoses than currently used methods.

Effect of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylori: a randomized, controlled trial.

AIM: To study the effects of drug treatment on hyperplastic gastric polyps infected with Helicobacter pylori (H pylori). METHODS: Forty-eight patients with hyperplastic gastric polyps (3-10 mm in diameter) infected with H pylori were randomly assigned to a treatment group (n = 24) which received proton-pump inhibitor (omeprazole or lansoprazole), clarithromycin, bismuth citrate and tinidazole, and a control group (n = 24) which received protective agent of gastric mucosa (tepretone). Patients underwent endoscopy and H pylori examination regularly before enrollment and 1-12 mo after treatment. RESULTS: Twenty-two patients in the treatment group and 21 in the control group completed the entire test protocol. In the treatment group, polyps disappeared 1-12 mo (average, 6.5+/-1.1 mo) after the treatment in 15 of 22 patients (68.2%) and H pylori infection was eradicated in 19 of the 22 patients (86.4%). However, 12 months after the study, no change in polyps or H pylori status was seen in any controls ((b)P<0.01). CONCLUSION: Most hyperplastic gastric polyps disappear after eradication of H pylori.

Preventive effects of geranylgeranylacetone on rat ethanol-induced gastritis.

AIM: To establish a rat ethanol gastritis model, we evaluated the effects of ethanol on gastric mucosa and studied the preventive effects of geranylgeranylacetone on ethanol-induced chronic gastritis. METHODS: One hundred male Sprague-Dawley rats were randomly divided into 4 equal groups: normal control group, undergoing gastric perfusion of normal saline (NS) by gastrogavage; model control group and 2 model therapy groups that underwent gastric perfusion with ethanol (distillate spirits with 56% ethanol content) by gastrogavage for 4 wk. Low or high doses of geranylgeranylacetone were added 1 h before ethanol perfusion in the 2 model therapy groups, while the same amount of NS, instead of geranylgeranylacetone was used in that model control group. The rats were then sacrificed and stomachs were removed. The injury level of the gastric mucosa was observed by light and electron microscopy, and the levels of prostaglandin 2 (PGE2), endothelin-1 (ET-1) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method. RESULTS: The gastric mucosal epidermal damage score (EDS; 4.5) and ulcer index (UI; 12.0) of the model control group were significantly higher than that of the normal control group (0 and 0 respectively, all P = 0.000). The gastric mucosal EDS and UI of the 2 model therapy groups (EDS: 2.5 and 2.0; UI: 3.5 and 3.0) were significantly lower than that of the model control group (all P < 0.01). There was no statistically significant difference between the low-dose and high-dose model therapy groups. The expression value of plasma ET-1 of the model control group was higher than that of the normal control group (P < 0.01) and the 2 model therapy groups (all P < 0.01). The expression values of gastric mucosal PGE2 and serum NO of the model control group were lower than those of the normal control group (all P < 0.05) and the 2 model therapy groups (all P < 0.05). The thickness of the gastric mucous layerand the hexosamine content in the model control group were significantly lower than that in the normal control group (all P < 0.01) and the 2 model therapy groups (all P < 0.05). Scanning and transmission electron microscopy observation showed that in the model control group, the epithelial junctions were vague, the intercellular joints disappeared and damage of the intracellular organelles were significantly worse than those in the normal control group. However, in the 2 model therapy groups, damage to the intercellular joints and organelles was ameliorate relative to the model control group. CONCLUSION: Administration of geranylgeranylacetone was correlated with a more favorable pattern of gastric mucosa damage after ethanol perfusion. The mechanism could be related to regulation of ET-1, NO and PGE2.