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目的 :探讨HO - 1-CO -cGMP和NOS -NO -cGMP细胞信号转导通路在八肽胆囊收缩素 (CCK -8)逆转内毒素血症大鼠低血管反应性中的作用。方法 :按照整体用药将大鼠分为 4组 :对照组、LPS组、CCK组及CCK +LPS组 ;用离体血管环张力测定技术 ,观察胸主动脉环 (TARs)对苯肾上腺素 (PE)累积收缩反应 ;分别用一氧化碳 (CO)供体正铁血红素 (He)、血红素氧合酶 1(HO - 1)抑制剂锌原卟啉 (ZnPP -IX)、一氧化氮合酶 (NOS)底物L-精氨酸 (L -Arg)、诱生型一氧化氮合酶 (iNOS)选择性抑制剂氨基胍 (AG)、NOS抑制剂Nω-硝基 -L -精氨酸 (L -NNA)、鸟苷酸环化酶 (sGC)抑制剂亚甲兰 (MB)预孵育后 ,测定TARs对PE的收缩反应。结果 :单独应用CCK - 8对血管张力无明显影响 ;预先注射CCK - 8可明显逆转LPS所致的低血管反应性 ;LPS及CCK +LPS组TARs用ZnPP -IX或AG孵育 ,可部分逆转这种低血管反应性 ;经L -NNA或MB孵育 ,可使低血管反应恢复正常 ;用He或L -Arg孵育可不同程度加重低血管反应状态。结论 :CCK - 8本身不激活HO - 1和iNOS ,但可影响LPS诱导的HO - 1和iNOS活性上升 ,减少CO/NO合成 ,从而使cGMP含量下降 ,对逆转内毒素血症大鼠低血管反应性有重要作用
AIM: To investigate the role of HO-1-CO-cGMP and NOS-NO-cGMP signal transduction pathway in the reversion of low blood vessel reactivity in endotoxemic rats induced by octapeptide cholecystokinin (CCK-8). Methods: The rats were divided into 4 groups: control group, LPS group, CCK group and CCK + LPS group according to the overall medication; the effects of thoracic aortic rings (TARs) on phenylephrine Cumulative contractile responses were observed. Carbon monoxide (CO) donor Heme, Heparin - 1 (ZnPP-IX), Nitric oxide synthase NOS) substrate L-arginine (L-Arg), selective inhibitors of inducible nitric oxide synthase (iNOS) aminoguanidine (AG), NOS inhibitor Nω-nitro-L-arginine L-NNA) and guanylate cyclase (sGC) inhibitor methylene blue (MB), the contractile response of TARs to PE was measured. Results: CCK - 8 alone had no significant effect on vascular tone. Pre - injection of CCK - 8 significantly reversed the hypotensive effect induced by LPS. TPSs incubated with ZnPP - IX or AG in LPS and CCK + LPS groups partially reversed this Hypoxia-induced hypoxemic reactivity can be restored to normal by incubation with L-NNA or MB. Incubation with He or L-Arg may aggravate the hypotensive response to varying degrees. CONCLUSION: CCK - 8 itself does not activate HO - 1 and iNOS, but it can affect the LPS - induced increase of HO - 1 and iNOS activity and decrease the synthesis of CO / NO, thus decreasing the content of cGMP. Reactivity plays an important role