Expression and clinical significance of NLRP1 and NLRP3 in colonic tissues of patients with ulcerative colitis / 西安交通大学学报(医学版)

【Objective】 To investigate the expressions of NLRP1 and NLRP3 in the colon of ulcerative colitis (UC) patients and analyze the correlation of the expressions with severity of UC, endoscopic manifestations and related laboratory indicators. 【Methods】 We collected biopsical specimens obtained with colonoscopy in 46 patients with UC (22 mild cases and 24 moderate to severe cases) and 20 cases of normal control group. We used the disease activity index to evaluate the Mayo UC inflammatory activity and immunohistochemical method to detect the protein expression levels of intestinal mucosal NLRP1 and NLRP3 in the tissue. RT-PCR was used to detect the expressions of NLRP1 and NLRP3 mRNA in intestinal mucosal tissues. Meanwhile, the colonoscopy, serum uric acid, C-reactive protein, serum sedimentation rate, platelet count, low-density lipoprotein, and cholesterol of UC patients were also counted to further analyze the relationship between NLRP1 and NLRP3. 【Results】 The expressions of NLRP1 and NLRP3 protein and mRNA in colonic mucosal tissues of UC patients were significantly higher than those of normal controls (P<0.05). Compared with that in mild UC, the expression of NLRP1 in colonic mucosal tissues of moderate and severe UC patients was significantly increased (P<0.05). There was no significant difference in the expressions of NLRP1 and NLRP3 in colonic mucosal tissues of UC patients with different lesion ranges. NLRP1 expression was positively correlated with Mayo overall score, Mayo endoscopic score, erythrocyte sedimentation rate, and C-reactive protein (P<0.05), NLRP3 expression was positively correlated with C-reactive protein (P<0.05), but not correlated with Mayo overall score, Mayo endoscopic score, or erythrocyte sedimentation rate. NLRP1 expression was positively correlated with low-density lipoprotein and platelet (P<0.05), but not with uric acid or cholesterol. NLRP3 was positively correlated with low-density lipoprotein, uric acid and cholesterol (P<0.05), but not with platelet. 【Conclusion】 NLRP1 and NLRP3 may be involved in the pathogenesis of UC and related to disease activity. Therefore, they can be used as molecular targets for targeted therapy, and NLRP1 can be used as a predictor of mucosal healing.

Water-infusion technique improved the bowel cleanliness during withdrawing the colonscopy：a randomized controlled study / 中国内镜杂志

Objective To compare the effect of water-infusion colonoscopy and conventional air-infusion colonoscopy on the bowel cleanliness during withdrawing.Methods A single blind randomized controlled trial was conducted. 222 patients were randomly divided into water-infusion group (group A, 112 cases) and air-infusion group (group B, 110 cases). The cleanliness scores, scores improvement, pain scores, time of reaching cecum, depth of colonoscopy, rate of whole colon examination, adenoma detection rate (ADR), operator’s dififculty and complications were compared between the two groups.Results The cleanliness score during withdrawing was higher in group A [M(8)/IQR(1) vs M(8)/IQR(2),P = 0.000], the improvement was higher in group A [(0.53 ± 0.74) vs (0.23 ± 0.55), P = 0.000], the abdominal pain score was signiifcantly lower in group A [M(2)/IQR(1) vs M(4)/IQR(2),P = 0.000] and the ADR was higher in group A (36.61 % vs 23.64 %,P = 0.041). The operator’s dififculty evaluation score was signiifcantly lower in group A [M(1)/IQR(1) vs M(2)/IQR(1),P = 0.005]. There were no signiifcant differences at the time of reaching cecum, the depth of colonoscopy and the whole colon examination rate between the two groups.Conclusion Water-infusion colonoscopy could signiifcantly improve the bowel cleanliness during withdrawing scope, improve the ADR and reduce abdominal pain of patients, without increasing the time to reach cecum.

Experimental Colitis Model Induced by DSS and TNBS in Rats:A Comparative Study / 胃肠病学

Background:As the empirical studies on human body are restricted extremely,the establishment and selection of suitable animal models are important for researches on ulcerative colitis( UC ). Aims:To compare the symptoms and colonic pathology of rat models with experimental colitis induced by dextran sulfate sodium( DSS ) and trinitrobenzene sulfonic acid( TNBS),so as to provide a reference for selecting animal models in UC-related studies. Methods:Drinking 4% DSS freely for 7 days or intrarectal administration of single dose 100 mg/kg TNBS-50% ethanol were used to establish experimental colitis model in Sprague-Dawley rats. The disease activity index( DAI)was assessed dynamically during the course of experiment. The whole colon was removed in batches for measurements of colonic damage score and activity of myeloperoxidase(MPO)at different time points. Results:The DAI score reached the peak at the 7th day and the 2nd day in DSS group and TNBS group,respectively,and decreased gradually afterwards. Six and one deaths occurred during the experimental course in DSS and TNBS groups,respectively. In DSS group,the duration of inflammation was short,the colonic injury was moderate and recovered after drug withdrawal. At the 18th day,the colonic damage score and MPO activity was 0. 25 ± 0. 50 and(0. 80 ± 0. 33)U/g,respectively,and no significant differences were seen between DSS group and normal control group. In TNBS group,the duration of inflammation was longer and the colonic injury was more severe. At the 21st day,the colonic damage score and MPO activity was 3. 60 ± 0. 55 and( 1. 60 ± 0. 39 ) U/g, respectively,and chronic inflammation was observed histologically. Conclusions:Both DSS and TNBS can induce experimental colitis model in rats. The course of TNBS-induced colitis model presents a transformation of acute to chronic inflammation,and may be more suitable for treatment-related studies of UC.

Camostat mesilate, a protease inhibitor, inhibits visceral sensitivity and spinal c-fos expression in rats with acute restraint stress / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of gut protease activity on visceral hypersensitivity in rats with acute restraint stress.</p><p><b>METHODS</b>Sprague-Dawley rats were given 30, 100 or 300 mg/kg camostat mesilate (CM), a protease inhibitor, or saline intragastrically 30 min before acute restraint stress induced by wrapping the fore shoulders, upper forelimbs and thoracic trunk for 2 h. Visceral perception of the rats was quantified as the visceral motor response with an electromyography, and the rectal mucosa and feces protease activity and spinal c-fos expression were measured.</p><p><b>RESULTS</b>CM dose-dependently reduced visceral sensitization elicited by rectal distension, but these doses did not completely inhibit stress-induced visceral sensitization. In normal rats, c-fos expression was found mainly in the superal spinal cord dorsal horn, and after the administration the CM, c-fos-positive cells decreased significantly in all dose groups (P<0.05). In 30 mg/kg CM group, fecal and rectal mucosal protease activity significantly decreased as compared with that in the stress group (P<0.05), and as CM dose increased to 100 and 300 mg/kg, the protease activity decreased even further (P<0.01).</p><p><b>CONCLUSION</b>The gut protease is involved in acute stress-induced visceral hypersensitivity, and CM can lower the visceral sensitivity and spinal c-fos expression in rats.</p>