Regulation of Colonic Mucosal MicroRNA Expression via Multiple Targets in Visceral Hypersensitivity Rats by Tongxieyaofang

PURPOSE: This study aimed to screen for differentially expressed microRNAs (miRNAs) in the colons of rats with visceral hypersensitivity to build the expression profiles of miRNAs therein and to determine the mechanism of Tongxieyaofang use in the treatment of irritable bowel syndrome (IBS). MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided randomly into four groups: control group, model control group (induced by rectum stimulus and evaluated by abdominal withdraw reaction), treatment control group (normal saline), and Tongxieyaofang group (treated with Tongxieyaofang). We screened for differential expression of colonic mucosal miRNAs using liquid chip technology and verified the expression thereof using reverse transcription-PCR. RESULTS: The visceral hypersensitivity rat model was successfully established. We found the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 to be up-regulated (p < 0.05), while the expression of miR-24, miR-31a, miR-192, miR-221, and miR-223 was down-regulated (p < 0.05) in the visceral hypersensitivity rats. After treatment with Tongxieyaofang, the expression of let-7f, let-7i, miR-130b, miR-29a, miR-132, miR-21, and miR-375 was reduced (p < 0.05), whereas the expression of miR-24, miR-31a, miR-192, miR-221, miR-223 was increased, compared to the treatment control group (p < 0.05). CONCLUSION: MiRNAs play a pivotal role in visceral hypersensitivity and might be targets in the treatment of IBS by Tongxieyaofang.

The effects of milk and milk products on non-steroidal anti-inflammatory drug induced intestinal damage in rats / 中华内科杂志

ObjectiveTo investigate the effect of milk and milk products on morphological structure and epidermal growth factor (EGF) of non-steroidal anti-inflammatory drugs (NSAIDs) induced small intestinal damage in animals.Methods Eighty male SD rats were randomly divided into 5 groups:control group,diclofenac group,diclofenac with 10% low fat milk group,diclofenac with 10% colostrum group and diclofenac with yoghurt group.The animals with milk or colostrum or yoghurt were fed for 5 days before the administration of diclofenac with 15 mg/kg by gavage,once.Then they were observed the scores of anatomical lesion and the scores of tissue damage of mucous membrane and the height of villous at the 24th and 48th hour after making the models.Observation of the change of ultrastructural organization of mucous membrane was carried out with transmission and scanning electron microscope and immunohistocbemistry of EGF.Results The scores of anatomical lesion and tissue damage of mucous membrane of the colostrum group were lower than those of the diclofenac group ( P ＜ 0.05 ).The heights of the pile on small intestine of the24th and 48th hour of the colostrum group were (145.7 ± 16.5) μm and (139.2 ± 19.0) μm,respectively.They were higher than those of the diclofenac group[( 119.2 ± 19.2 ) μm and ( 105.4 ± 18.4 )μm,P ＜ 0.05].However there was no difference of the scores and the height among diclofenac group,milk group and yoghurt group.TEM and SEM of tissues showed that the cytoplasmic membrane and other cellular components of villous epithelial cells were well preserved in colostrum group,and the microvilli in the milk group and yoghurt group were ablated more obviously.The positive area of EGF of small intestine [(6170.5 ± 1483.9) μm2]were higher 48 h after administration of diclofenac compared with the diclofenac group ( P ＜ 0.05 ).The expression of EGF in milk and yoghurt group were no significant statistical difference with the diclofenac group.ConclusionBovine colostrum may have a beneficial effect in prevention of NSAIDs induced small intestinal injuries and preserve mechanical barrier of small intestinal mucosa which is probably relative to EGF.

Influence of tongxie prescription on CRF expression in spinal cord and brain of hypersensitive viscera rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the distribution and expression of corticotropin releasing factor (CRF) in spinal cord, hypothalamus and third ventricle of cerebrum, of the hypersensitive viscera rats, and to research on the mechanism of CRF in the hypersensitive vicera signal conduction pathway in IBS (irritable bowel syndrome) and to investigate possible active mechanisms of tongxie prescription on IBS.</p><p><b>METHOD</b>Forty SD rats were divided randomly into three groups. The rats of model No. 1 were sensitized by injecting egg albumin into abdominal cavity. The rats of model No. 2 were sensitised by conditional stimulus and unconditional stimulus. The two model groups were both divided randomly into two groups. The five groups were given intragastric administration with Tongxie prescription or normal saline for four weeks. Then quantitative analysis of CRF in the lumbosacral spinal cord and brain of rats were achieved by immunohistochemical method and computerized image system.</p><p><b>RESULT</b>The sensitivity of the groups being treated with tongxie prescription were much lower than the model groups (P < 0.01). The immunohistochemical method showed that CRF was expressed in the lumbar intumescentia of spinal cord, hypothalamus and the diaphragmatic surface of third ventricle of cerebrum. The CRF positive index of the model groups was higher than that of the blank group (P < 0.01). The CRF positive index of the healing groups was lower than that of the model groups (P < 0.01). The CRF positive index of the healing groups was higher than that of the blank group (P < 0.01).</p><p><b>CONCLUSION</b>The two model rats evoked by two different stimulation both appeared visceral hypersensitivity state. CRF is related to stress. The increase of CRF expression in the lumbar intumescentia of spinal cord, hypothalamus and the diaphragmatic surface of third ventricle of cerebrum showed that CRF is critical to the introduce of stimulus signal of vicera. Tongxie prescription can significantly decrease CRF expression. This is one mechanism to decrease sensitivity of hypersensitive viscera rats.</p>

Follow-up study on corticosteroid treatment of inflammatory bowel disease / 中华消化杂志

Objective To retrospectively analyze the effect of corticosteroids therapy for inflammatory bowel disease (IBD) at 1-month and 1-year. Methods Those who was diagnosed as Crohn's disease (CD, n=55) or ulcerative colitis (UC, n= 154) from 1998 to 2006 were investigated. The effect of corticosteroids was evaluated after one month and 1-year. The prognostic factors were calculated using Logistic regression analysis. Results The patients who received eortieosteroids therapy were 21 (38.2%) with CD and 20 (13.0%) with UC (2 cases withdrawn). In one month followe-up, the complete and partial remissions were found in 15 (71.4%) and 3 (14.3%) patients with CD, respectively, while there were 15 (83.3%) and 3 (16.7%) in patients UC, respectively. Only 3 (14.3%) patients with CD was no response. In one year follow up, 11 out of 21 (52.4%) patients with CD had prolonged response to corticosteroids, 6 (28.6%) were corticosteroid dependence, and 4 (19%) required surgery; whereas 11 out of 18 (61.1%) patients with UC had prolonged response, 3 (16.7%) were corticosteroid dependence, and 4 (22.2%) required surgery. Logistic regression analysis showed that serum albumin level was associated with efficacy of corticosteroids after one year (P= 0.027, OR: 1.320,95% CI: 1.032~1. 690). Conclusion The IBD patients who has response to initiating corticosteroids therapy will get shor-term remission. Its prognosis is related with serum albumin level.