AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following c...AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.展开更多
Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-...Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis, and to investigate the possible mechanism of SQR in regulating intestinal dynamics. Methods Sixty rats were randomly divided into normal control, model Ⅰ , model Ⅱ, mesalazine, and high-dose, and low-dose SQR groups with 10 rats in each group. TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis. On the 4th day after administration of TNBS, each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days: 600 mg·kg^-1·d^-1 mesalazine, 2.4g^-1·d^-1 SQR, and 1.2g^-1·d^-1 SQR. Model Ⅱ rats received normal saline solution. After 7 days colonic samples were collected. While the colonic samples of model I group were collected on the 3rd day after TNBS administered. Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope. Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot. Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury, and administration of SQR or mesalazine reduced the severity of injury. Similarly, the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P〈0.05). Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P〈0.05), especially the high-dose SQR group. Conclusion SQR could alleviate and repair the injured ICC, and improve its quantity, which might be involved in regulating intestinal motility.展开更多
5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mecha...5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.展开更多
Sea cucumber is a food with nutritional benefits distributing mainly in Asia, and Apostichopus japonicus (A. japonicus) is a kind of sea cucumber whose quality is better than any others. However, different processing ...Sea cucumber is a food with nutritional benefits distributing mainly in Asia, and Apostichopus japonicus (A. japonicus) is a kind of sea cucumber whose quality is better than any others. However, different processing methods make various effect on its quality. In this study, we evaluated the protection effect of A. japonicus with different processing methods on mice with ulcerative colitis induced by trinitrobenzene sulfonic acid (TNBS), especially on the intestinal microflora. The expression of IFN-γ/IL-4 and IL-1β in gut, and intestinal microbiota were discussed. The results revealed that three different processing methods of A. japonicus could decrease the expression of inflammatory cytokines, except for the expression of IFN-γ/IL-4 treated with enzymatic, and dried A. japonicus was the most efficient. A. japonicus could change the microbiotic imblance relatively back to normal in terms of bacterial diversity and composition, meanwhile increase the abundance of Bifidobacteria, Lactobacillus and Clostridium leptum. The elements of protein, polysaccharide in dried, instant, enzymatic A. japonicus are 73.09%, 65.06%, 57.42% and 6.72%, 5.46%, 5.45% respectively. This study indicated that A. japonicus have a good improving effect on ulcerative colitis, especially on the microbiome, and processing methods had an effect on alleviation of ulcerative colitis, which might be associated with content of protein and polysaccharide.展开更多
Objective: The aim is to observe the protective effect of baicalin on trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice and explore its mechanism. Methods: The mice were divided into 4 groups: ...Objective: The aim is to observe the protective effect of baicalin on trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice and explore its mechanism. Methods: The mice were divided into 4 groups: ethanol control group, TNBS model group, baicalin low-dose group and baicalin high-dose group. The model of experimental colitis in mice was induced by TNBS enema. After 2 hours of TNBS enema, baicalin was given by gavage, QD × 7D. The animals were sacrificed on the 8th day to observe the extent of colonic mucosal damage, and the Peroxidase activity, Malondialdehyde (MDA) and glutathione (GSH) contents were measured. Results: Compared with the TNBS model group, the body weight, gross injury score and histological changes were significantly improved;MPO enzyme activity and MDA content were significantly decreased in the low and high-dose baicalin groups;and the content of glutathione increased. Conclusion: Baicalin can alleviate TNBS-induced colitis in mice, and the mechanism is related to the antioxidation of baicalin.展开更多
目的:研究加味藿香正气软胶囊(Jiawei Huoxiang Zhengqi soft capsule,JWHXZQ)对三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid TNBS)诱导小鼠结肠炎模型的抗炎作用及其机制.方法:将50只B a l b/c♀小鼠随机分为对照组、模型组、J ...目的:研究加味藿香正气软胶囊(Jiawei Huoxiang Zhengqi soft capsule,JWHXZQ)对三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid TNBS)诱导小鼠结肠炎模型的抗炎作用及其机制.方法:将50只B a l b/c♀小鼠随机分为对照组、模型组、J W H X Z Q低、中、高剂量(0.234、0.468、0.936 g/kg)组.采用TNBS/乙醇灌肠制作小鼠结肠炎模型,同时开始每天ig给药,连续7 d.每天进行疾病活动指数(disease activity index,DAI)评分,7 d后处死小鼠,对各组小鼠结肠进行组织病理学评分检测血清中NO水平、结肠组织中髓过氧化物酶(myeloperoxidase,MPO)含量及白介素(interleukin,IL)-1β、IL-6、IL-12、肿瘤坏死因子(tumor necrosis factor,TNF)-α、干扰素(interferon,IFN)-γ等促炎性细胞因子水平.结果:与模型组比较,JWHXZQ中、高剂量组治疗可显著降低TNBS结肠炎小鼠的DAI评分和病理学评分,降低小鼠血清中NO水平,同时还显著降低结肠中MPO含量、IL-1β、IL-6、IL-12和TNF-α等促细胞因子水平;JWHXZQ低剂量组也能显著降低小鼠血清中NO含量、结肠中IL-1β和IL-6水平.结论:JWHXZQ对TNBS诱导的小鼠结肠炎具有一定治疗作用,其机制可能与抑制促炎性细胞因子产生及相关免疫应答通路而发挥作用.展开更多
基金Supported by Hong Kong Jockey Club Institute of Chinese Medicine,No.JCICM-4-07
文摘AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.
基金Supported by the Shanghai Committee of Science and Technology Foundation for Research Discipline Project (06411941)the Shanghai Leading Academic Discipline Project (J50305)
文摘Objective To observe the influence of Shenqing Recipe (SQR), a kind of Traditional Chinese Medicine, on the morphology and quantity of colonic interstitial ceils of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis, and to investigate the possible mechanism of SQR in regulating intestinal dynamics. Methods Sixty rats were randomly divided into normal control, model Ⅰ , model Ⅱ, mesalazine, and high-dose, and low-dose SQR groups with 10 rats in each group. TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis. On the 4th day after administration of TNBS, each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days: 600 mg·kg^-1·d^-1 mesalazine, 2.4g^-1·d^-1 SQR, and 1.2g^-1·d^-1 SQR. Model Ⅱ rats received normal saline solution. After 7 days colonic samples were collected. While the colonic samples of model I group were collected on the 3rd day after TNBS administered. Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope. Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot. Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury, and administration of SQR or mesalazine reduced the severity of injury. Similarly, the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P〈0.05). Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P〈0.05), especially the high-dose SQR group. Conclusion SQR could alleviate and repair the injured ICC, and improve its quantity, which might be involved in regulating intestinal motility.
基金supported by grants from the National Natural Science Foundation of China(No.81072431)the Innova-tion Foundation of Huazhong University of Science and Tech-nology(No.2010MS027)
文摘5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.
文摘Sea cucumber is a food with nutritional benefits distributing mainly in Asia, and Apostichopus japonicus (A. japonicus) is a kind of sea cucumber whose quality is better than any others. However, different processing methods make various effect on its quality. In this study, we evaluated the protection effect of A. japonicus with different processing methods on mice with ulcerative colitis induced by trinitrobenzene sulfonic acid (TNBS), especially on the intestinal microflora. The expression of IFN-γ/IL-4 and IL-1β in gut, and intestinal microbiota were discussed. The results revealed that three different processing methods of A. japonicus could decrease the expression of inflammatory cytokines, except for the expression of IFN-γ/IL-4 treated with enzymatic, and dried A. japonicus was the most efficient. A. japonicus could change the microbiotic imblance relatively back to normal in terms of bacterial diversity and composition, meanwhile increase the abundance of Bifidobacteria, Lactobacillus and Clostridium leptum. The elements of protein, polysaccharide in dried, instant, enzymatic A. japonicus are 73.09%, 65.06%, 57.42% and 6.72%, 5.46%, 5.45% respectively. This study indicated that A. japonicus have a good improving effect on ulcerative colitis, especially on the microbiome, and processing methods had an effect on alleviation of ulcerative colitis, which might be associated with content of protein and polysaccharide.
文摘Objective: The aim is to observe the protective effect of baicalin on trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice and explore its mechanism. Methods: The mice were divided into 4 groups: ethanol control group, TNBS model group, baicalin low-dose group and baicalin high-dose group. The model of experimental colitis in mice was induced by TNBS enema. After 2 hours of TNBS enema, baicalin was given by gavage, QD × 7D. The animals were sacrificed on the 8th day to observe the extent of colonic mucosal damage, and the Peroxidase activity, Malondialdehyde (MDA) and glutathione (GSH) contents were measured. Results: Compared with the TNBS model group, the body weight, gross injury score and histological changes were significantly improved;MPO enzyme activity and MDA content were significantly decreased in the low and high-dose baicalin groups;and the content of glutathione increased. Conclusion: Baicalin can alleviate TNBS-induced colitis in mice, and the mechanism is related to the antioxidation of baicalin.
文摘目的:研究加味藿香正气软胶囊(Jiawei Huoxiang Zhengqi soft capsule,JWHXZQ)对三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid TNBS)诱导小鼠结肠炎模型的抗炎作用及其机制.方法:将50只B a l b/c♀小鼠随机分为对照组、模型组、J W H X Z Q低、中、高剂量(0.234、0.468、0.936 g/kg)组.采用TNBS/乙醇灌肠制作小鼠结肠炎模型,同时开始每天ig给药,连续7 d.每天进行疾病活动指数(disease activity index,DAI)评分,7 d后处死小鼠,对各组小鼠结肠进行组织病理学评分检测血清中NO水平、结肠组织中髓过氧化物酶(myeloperoxidase,MPO)含量及白介素(interleukin,IL)-1β、IL-6、IL-12、肿瘤坏死因子(tumor necrosis factor,TNF)-α、干扰素(interferon,IFN)-γ等促炎性细胞因子水平.结果:与模型组比较,JWHXZQ中、高剂量组治疗可显著降低TNBS结肠炎小鼠的DAI评分和病理学评分,降低小鼠血清中NO水平,同时还显著降低结肠中MPO含量、IL-1β、IL-6、IL-12和TNF-α等促细胞因子水平;JWHXZQ低剂量组也能显著降低小鼠血清中NO含量、结肠中IL-1β和IL-6水平.结论:JWHXZQ对TNBS诱导的小鼠结肠炎具有一定治疗作用,其机制可能与抑制促炎性细胞因子产生及相关免疫应答通路而发挥作用.
