Enterocyte Response to Ischemia Is Dependent on Differentiation State,

摘要: Enterocytes at the tips of microvilli are more sensitive to an ischemic insult than those cells residing in crypts, effect thought be due a relative lack collateral flow. We speculated that this increased cellular sensitivity ischemia might intrinsic feature related their differentiated phenotype. To test hypothesis, enterocyte response was determined using both vivo and vitro models. For studies, male Sprague-Dawley rats underwent laparotomy, small intestinal induced by clamping superior mesenteric artery for 30 or 60 minutes, after which reperfusion allowed various time points up 4 days. Injury assessed histologically, as well with Northern blots, probing differentiation markers alkaline phosphatase lactase, gut-epithelial marker villin. Mucosal changes consistent ischemia/reperfusion injury were evident—that is, rapid inflammatory followed progressive villus cell loss beginning progressing depending on degree insult, eventual return normal microanatomy. Intestinal lactase lost immediately returned reperfusion, confirming particularly injury. The studies employed two separate models differentiation: sodium butyrate-treated HT-29 Caco-2 maintained 7 days confluence. In models, undifferentiated subjected treatment 2-deoxyglucose oligomycin-A (in model ischemia) apoptosis fluorescence-activated sorting analysis. Differentiation lines resulted significantly greater apoptotic compared exposed identical insult. conclude enterocytes may inherently ischemia-induced counterparts. These findings call into question popularly held belief tip susceptible because location microvascular anatomy.