AIM： To evaluate the protective effects of ilomastat, an exogenous matrix metalloproteinase （MMP） inhibitor, on trinitrobenzenesulfonic acid （TNB）-induced ulcerative colitis （UC） in rats. METHODS： Male SD rats...AIM： To evaluate the protective effects of ilomastat, an exogenous matrix metalloproteinase （MMP） inhibitor, on trinitrobenzenesulfonic acid （TNB）-induced ulcerative colitis （UC） in rats. METHODS： Male SD rats were randomly divided into model group, protective groups A and B, and normal control group. Rats in the model group received only intra-colonic TNB. Rats in the protective groups A and B received intra-peritoneal ilomastat of 10 mg/kg and 20 mg/kg, respectively, beside TNB. Rats in the normal control group received only intra-colonic normal saline. After 3 wk, segments of colon were obtained. RT-PCR and immunohistochemistry were used to examine the expression of MMP-1 and TIMP-1. Hematoxylin-eosin （HE） staining was used for pathological study. RESULTS： The model of UC was successfully induced in rats. Inflammation of colonic mucosa greatly improved in protective groups A and B. Expression of MMP-1 and TIMP-1 in the model group, protective groups A and B was significantly higher than that in the normal control group （P 〈 0.0001） with MMP-1 expression increased more significantly than TIMP-1 expression. Expression of MMP-1 in protective groups A and B was significantly lower than that in the model group （P 〈 0.0001）. Expression of MMP-1 in protective group B was significantly lower than that in protective group A （P 〈 0.0001）. CONCLUSION： IIomastat improves TNB-induced UC in rats by inhibiting the MMP-1 activity.展开更多
AIM： To investigate the response of astrocytes and neurons in rat lumbo±sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS： Thirty-three...AIM： To investigate the response of astrocytes and neurons in rat lumbo±sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS： Thirty-three male Sprague-Dawley rats were randomly divided into two groups： experimental group （n = 17）, colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid （TNBS）; control group （n = 16）, saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein （GFAP）, Fos and GFAP/Fos immunohistochemistry. RESULTS： Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae （laminae Ⅰ-Ⅱ） of dorsal horn, intermediolateral nucleus （laminae Ⅴ）, posterior commissural nucleus （laminae Ⅹ） and anterolateral nucleus （laminae Ⅸ）. Fos-IR （Fos-immunoreactive） neurons were mainly distributed in the deeper laminae of the spinal cord （laminae Ⅲ-Ⅳ, Ⅴ-Ⅵ）. In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone （MVZ）. The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls （50.44±16.8, 29.24±6.5, 24.14±5.6, P〈0.05）. The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration （34.34±2.5, P〈0.05）. After 28 d of TNBS administration, the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls （18.04±4.9, 14.64±6.4, P〉0.05）. CONCLUSION： Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity ofastrocytes in the spinal cord and medulla oblongata is reduced.展开更多
OBJECTIVE: To investigate how compound Sophorae decoction(CSD) works on rats' models of ulcerative colitis(UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) by metabolomics studies of colon, liver, ...OBJECTIVE: To investigate how compound Sophorae decoction(CSD) works on rats' models of ulcerative colitis(UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) by metabolomics studies of colon, liver, and kidney tissue extracts.METHODS: Rats with UC induced by TNBS enema were used as models in this study. Metabolic profiles of the three tissues were analyzed and pathway analysis of biomarkers was performed after CSD administration and further integration of metabolic networks.RESULTS: Thirteen biomarkers were screened from colon, liver, and kidney tissue extracts, and the levels of these substances were up-or down-regulated in the model group, but their levels were reversed after CSD administration. These biomarkers were mainly related to Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, Glutathione metabolism, Arachidonic acid metabolism, Nicotinate and nicotinamide metabolism,Alanine, aspartate and glutamate metabolism.CONCLUSION: CSD could significantly ameliorate the symptoms of UC by regulating multiple metabolic pathways.展开更多
AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: The colonic myeloperoxidase (MPO) activity and tumor necro...AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-(TNF- ) level were determined. A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intracolonic injection of TNBS. RESULTS: TNBS group showed significantly elevated colonic MPO activity and increased TNF-level. The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively. Altered proteins were found to be involved in a number of biological functions, such as inflammation/immunity, cell signaling, redox regulation, sulfate transport and cellular metabolism. The over-expression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12) and low expression of proteasome subunit type-1 (psma) were validated by Western blotting analysis. CONCLUSION: TNBS-induced colitis has a profound impact on protein profiling in the nervous system. This result helps understand the neurological pathogenesis of inflammatory bowel disease.展开更多
文摘AIM： To evaluate the protective effects of ilomastat, an exogenous matrix metalloproteinase （MMP） inhibitor, on trinitrobenzenesulfonic acid （TNB）-induced ulcerative colitis （UC） in rats. METHODS： Male SD rats were randomly divided into model group, protective groups A and B, and normal control group. Rats in the model group received only intra-colonic TNB. Rats in the protective groups A and B received intra-peritoneal ilomastat of 10 mg/kg and 20 mg/kg, respectively, beside TNB. Rats in the normal control group received only intra-colonic normal saline. After 3 wk, segments of colon were obtained. RT-PCR and immunohistochemistry were used to examine the expression of MMP-1 and TIMP-1. Hematoxylin-eosin （HE） staining was used for pathological study. RESULTS： The model of UC was successfully induced in rats. Inflammation of colonic mucosa greatly improved in protective groups A and B. Expression of MMP-1 and TIMP-1 in the model group, protective groups A and B was significantly higher than that in the normal control group （P 〈 0.0001） with MMP-1 expression increased more significantly than TIMP-1 expression. Expression of MMP-1 in protective groups A and B was significantly lower than that in the model group （P 〈 0.0001）. Expression of MMP-1 in protective group B was significantly lower than that in protective group A （P 〈 0.0001）. CONCLUSION： IIomastat improves TNB-induced UC in rats by inhibiting the MMP-1 activity.
文摘AIM： To investigate the response of astrocytes and neurons in rat lumbo±sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS： Thirty-three male Sprague-Dawley rats were randomly divided into two groups： experimental group （n = 17）, colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid （TNBS）; control group （n = 16）, saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein （GFAP）, Fos and GFAP/Fos immunohistochemistry. RESULTS： Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae （laminae Ⅰ-Ⅱ） of dorsal horn, intermediolateral nucleus （laminae Ⅴ）, posterior commissural nucleus （laminae Ⅹ） and anterolateral nucleus （laminae Ⅸ）. Fos-IR （Fos-immunoreactive） neurons were mainly distributed in the deeper laminae of the spinal cord （laminae Ⅲ-Ⅳ, Ⅴ-Ⅵ）. In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone （MVZ）. The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls （50.44±16.8, 29.24±6.5, 24.14±5.6, P〈0.05）. The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration （34.34±2.5, P〈0.05）. After 28 d of TNBS administration, the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls （18.04±4.9, 14.64±6.4, P〉0.05）. CONCLUSION： Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity ofastrocytes in the spinal cord and medulla oblongata is reduced.
基金Supported by the Chinese National Natural Science Foundation (Immunomodulatory Mechanism of Bmsc Evs Mediated by Ephb2/Ephrin-b1 Pathway in Ulcerative Colitis and Synergistic Effect of Compound Sophorae decoction, No.81774093)。
文摘OBJECTIVE: To investigate how compound Sophorae decoction(CSD) works on rats' models of ulcerative colitis(UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution(TNBS) by metabolomics studies of colon, liver, and kidney tissue extracts.METHODS: Rats with UC induced by TNBS enema were used as models in this study. Metabolic profiles of the three tissues were analyzed and pathway analysis of biomarkers was performed after CSD administration and further integration of metabolic networks.RESULTS: Thirteen biomarkers were screened from colon, liver, and kidney tissue extracts, and the levels of these substances were up-or down-regulated in the model group, but their levels were reversed after CSD administration. These biomarkers were mainly related to Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, Glutathione metabolism, Arachidonic acid metabolism, Nicotinate and nicotinamide metabolism,Alanine, aspartate and glutamate metabolism.CONCLUSION: CSD could significantly ameliorate the symptoms of UC by regulating multiple metabolic pathways.
基金Supported by The Research Grants Council of Hong Kong,RGC-HKBU2/07CThe Hong Kong Jockey Club Institute of Chinese Medicine, JCICM4-07
文摘AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-(TNF- ) level were determined. A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intracolonic injection of TNBS. RESULTS: TNBS group showed significantly elevated colonic MPO activity and increased TNF-level. The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively. Altered proteins were found to be involved in a number of biological functions, such as inflammation/immunity, cell signaling, redox regulation, sulfate transport and cellular metabolism. The over-expression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12) and low expression of proteasome subunit type-1 (psma) were validated by Western blotting analysis. CONCLUSION: TNBS-induced colitis has a profound impact on protein profiling in the nervous system. This result helps understand the neurological pathogenesis of inflammatory bowel disease.
