The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorpt...The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.展开更多
目的观察三叶青水提物对慢性阻塞性肺疾病(COPD)大鼠基质金属蛋白酶9(Matrix met alloproteinases-9,MMP-9)和基质金属蛋白酶抑制剂-1(Matrix met alloproteinases inhibitor-1,TIMP-1)的影响,探讨三叶青对大鼠肺组织的作用机制。方法...目的观察三叶青水提物对慢性阻塞性肺疾病(COPD)大鼠基质金属蛋白酶9(Matrix met alloproteinases-9,MMP-9)和基质金属蛋白酶抑制剂-1(Matrix met alloproteinases inhibitor-1,TIMP-1)的影响,探讨三叶青对大鼠肺组织的作用机制。方法选择烟熏加气管内滴注内毒素(LPS)法复制COPD模型,将清洁级健康SD雄性大鼠30只,随机分为3组分别为对照组、模型组和三叶青组,每组10只。造模成功后肺组织采用HE染色观察病理改变,采用免疫组织化学方法测定大鼠肺组织中MMP-9和TIMP-1的表达,酶联免疫吸附法测定大鼠血清、支气管肺泡灌洗液和肺匀浆组织中MMP-9和TIMP-1的表达。结果光学显微镜下可见三叶青组大鼠炎症较模型组有所减轻。酶联免疫吸附法检测结果显示,模型组大鼠肺组织、血清和支气管肺泡灌洗液中MMP-9和TIMP-1含量较对照组显著增加(P<0.05),三叶青组的MMP-9和TIMP-1含量较模型组显著下降(P<0.05)。免疫组织化学检测结果显示,与对照组比较模型组肺组织中的MMP-9和TIMP-1表达明显增多,差异有统计学意义(P<0.05)。与模型组比较三叶青组肺组织中的MMP-9和TIMP-1表达减少,差异有统计学意义(P<0.05)。结论三叶青可能通过下调MMP-9、TIMP-1表达,调节MMP-9/TIMP-1失衡,进而干预气道重塑,延缓病变进展,这可能是其治疗COPD的作用机制之一。展开更多
文摘The gastrointestinal barrier is-with approximately 400 m^2-the human body's largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extraintestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.
文摘目的观察三叶青水提物对慢性阻塞性肺疾病(COPD)大鼠基质金属蛋白酶9(Matrix met alloproteinases-9,MMP-9)和基质金属蛋白酶抑制剂-1(Matrix met alloproteinases inhibitor-1,TIMP-1)的影响,探讨三叶青对大鼠肺组织的作用机制。方法选择烟熏加气管内滴注内毒素(LPS)法复制COPD模型,将清洁级健康SD雄性大鼠30只,随机分为3组分别为对照组、模型组和三叶青组,每组10只。造模成功后肺组织采用HE染色观察病理改变,采用免疫组织化学方法测定大鼠肺组织中MMP-9和TIMP-1的表达,酶联免疫吸附法测定大鼠血清、支气管肺泡灌洗液和肺匀浆组织中MMP-9和TIMP-1的表达。结果光学显微镜下可见三叶青组大鼠炎症较模型组有所减轻。酶联免疫吸附法检测结果显示,模型组大鼠肺组织、血清和支气管肺泡灌洗液中MMP-9和TIMP-1含量较对照组显著增加(P<0.05),三叶青组的MMP-9和TIMP-1含量较模型组显著下降(P<0.05)。免疫组织化学检测结果显示,与对照组比较模型组肺组织中的MMP-9和TIMP-1表达明显增多,差异有统计学意义(P<0.05)。与模型组比较三叶青组肺组织中的MMP-9和TIMP-1表达减少,差异有统计学意义(P<0.05)。结论三叶青可能通过下调MMP-9、TIMP-1表达,调节MMP-9/TIMP-1失衡,进而干预气道重塑,延缓病变进展,这可能是其治疗COPD的作用机制之一。
