肢体缺血预适应的小肠保护作用及与一氧化氮/内皮素-1的关系

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目的:观察一氧化氮/内皮素-1(NO/ET-1)失衡与肢体缺血再灌注(L/R)后小肠损伤的关系,以及缺血预适应(IPC)对NO/ET-1系统的调节作用。方法:雄性WISTAR大鼠18只,随机分为对照(CONTROL)组,缺血再灌注 (IR)组和缺血预适应(IPC+IR)组,每组6只,分别测定血浆和小肠组织二氨氧化酶(DAO)、一氧化氮(NO)、内皮素- 1(ET-1)、NO/ET-1比值的含量变化及小肠组织的髓过氧化物酶(MPO)、DNA双链百分率(RATIO OF DNA CHAIN%)、总一氧化氮合酶(TNOS)、诱导型一氧化氮合酶(INOS)、结构型一氧化氮合酶(CNOS)的水平;免疫组化法检测小肠组织的诱导型一氧化氮合酶(INOS)、内皮型一氧化氮含酶(ENOS)的表达。结果:IR组血浆和小肠组织NO、ET-1,血浆DAO 及组织MPO均明最高于对照组,而NO/ET-1的比值,组织DAO及DNA双链百分率明显少于对照组;小肠粘膜INOS 的表达及总NOS活性高于对照组,CNOS(主要为ENOS)的表达少于对照组。IPC+IR组血浆和小肠组织NO、ET-1, 血浆DAO及组织MPO均明显少于IR组,而NO/ET-1的比值,组织DAO及DNA双链百分率却明显高于IR组;小肠粘膜INOS的表达及总NOS活性少于IR组,CNOS(主要为ENOS)的表达高于IR组。结论:肢体I/R后小肠损伤与 NO/ET-1失衡有关,IPC对肢体IR继发的小肠粘膜损伤的拮抗作用可能通过对NO/ET-1系统的调节作用而介导, 此时内皮源的NO产生增加,非内皮源的NO产生减少。 Objective: To observe the relationship between the imbalance of nitric oxide / endothelin-1 (NO / ET-1) and intestinal injury after limb ischemia-reperfusion (L / R) and the effect of ischemic preconditioning System regulation. Methods: Eighteen male WISTAR rats were randomly divided into control group, IR group and IPC + IR group, with 6 rats in each group. The plasma and intestinal tissue were measured respectively (DAO), nitric oxide (NO), endothelin-1 (ET-1), NO / ET-1 ratio and the content of myeloperoxidase (MPO) (RATIO OF DNA CHAIN%), total nitric oxide synthase (TNOS), inducible nitric oxide synthase (INOS) and structural nitric oxide synthase (CNOS) were detected by immunohistochemistry. Inducible Nitric Oxide Synthase (INOS), Endothelial Nitric Oxide Enzyme (ENOS) Expression. Results: The levels of NO, ET-1, plasma DAO and tissue MPO in IR group were significantly higher than those in control group, while the ratio of NO / ET-1, the percentage of DAO and DNA double strand in group IR were significantly lower than that in control group; INOS expression and total NOS activity was higher than that of the control group, and the expression of CNOS (mainly ENOS) was less than that of the control group. NO, ET-1, plasma DAO and tissue MPO in IPC + IR group were significantly lower than those in IR group, but NO / ET-1 ratio, DAO and DNA double- Mucosal INOS expression and total NOS activity less than the IR group, CNOS (mainly ENOS) higher than the IR group. CONCLUSION: Post-I / R injury of the small intestine is associated with an imbalance of NO / ET-1. The antagonistic effect of IPC on intestinal mucosal injury secondary to limb IR may be mediated through the regulation of NO / ET-1 system, Increased NO production in the source and NO reduction in the non-endothelial source.
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