八肽胆囊收缩素对正常及脑缺血大鼠大脑皮层NO水平的调节作用

Regulation of cholecystokinin octapeptide on nitric oxide level in brain cortex in normal or brain ischemia rats

目的 探讨中枢八肽胆囊收缩素 ( CCK- 8)对正常及脑缺血大鼠脑组织一氧化氮 ( NO)水平的影响及其可能的机制。方法 给正常或局部脑缺血 1h再灌注 2 4h大鼠脑室内 ( icv)分别注射体积均为 5μl的溶剂 (人工脑脊液 )、CCK- 8、丙谷胺或丙谷胺 +CCK - 8。给药后 2 5 h分别取正常大鼠的大脑皮层及脑缺血大鼠缺血中心区、半暗区、非缺血半球皮层 ,检测脑组织 NO水平及一氧化氮合酶 ( NOS)活性。结果 ( 1)与假手术组相比 ,缺血溶剂组大鼠脑缺血中心区及半暗区 NO水平显著增加 ( P<0 .0 5 ) ,缺血 CCK- 8组 NO水平无明显变化 ;与缺血溶剂组相比 ,缺血 CCK - 8组脑缺血中心区及半暗区 NO水平显著降低 ( P<0 .0 5或 0 .0 1) ;缺血 CCK- 8组非缺血半球皮层NO水平显著高于假手术组 ( P<0 .0 5 ) ,而缺血溶剂组非缺血半球 NO水平的升高不明显。 ( 2 )正常大鼠给 CCK - 8后 ,脑皮层 NO水平、NOS活性明显升高 ( P<0 .0 5或 0 .0 0 5 ) ,丙谷胺可部分拮抗这一作用 ;单独给丙谷胺对 NO水平、NOS活性无影响。结论 中枢给予 CCK- 8对局部脑缺血再灌注引起的脑皮层缺血中心区及半暗区 NO水平的升高具有抑制作用 ;对正常脑皮层组织 NO水平、NOS活性有上调作用 ,丙谷胺可部分拮抗这一作用。

Objective To explore the effects of cholecystokinin-8(CCK-8) applied centrally on nitric oxide (NO)levels in brain cortexes of normal or brain ischemia rats and the mechanisms involved in these effects.Methods Vehicle (artificial cerebrospinal fluid), CCK-8, proglumide or proglumide+CCK-8 were injected intracerebroventricularly (icv) respectively in normal or focal cerebral ischemia rats with a total volume of 5μl. Brain cortexes of normal rats or ischemic core, penumbra, or nonischemic hemispheres cortexes of brain ischemia rats were dissected 25h after drug delivery for determination of NO levels or NOS activities. Results (1)There were significant increases of NO levels in ischemic core or penumbra in brain ischemia rats treated with vehicle( P <0.05),but not in brain ischemia rats treated with CCK-8 compared with sham-operated group; The NO levels of ischemic core or penumbra in CCK-8 treated group decreased significantly compared with vehicle treated group( P <0.05 or 0.01);The NO levels in nonischemic hemispheres of CCK-8 treated group were greater than those of sham-operated group( P <0.05), but the increases of NO levels in nonischemic hemispheres of vehicle treated group were not statistically significant. (2)CCK-8 could promote NO production and NOS activity of cortexes in normal rats( P <0.05 or 0.005) and proglumide could partially inhibit such actions of CCK-8; There were no effects of proglumide given alone on NO levels or NOS activities. Conclusion CCK-8 can inhibit the increase of NO level in ischemic core or penumbra induced by brain ischemia and reperfusion, and upregulate NO level and NOS activity in normal cortex, which can be antagonized partially by proglumide.