八肽胆囊收缩素抑制大鼠脊髓损伤后诱导型一氧化氮合酶的表达

Inhibition of cholecystokinin octapeptide on the expression of inducible nitricoxide synthase in rats with spinal cord injury

目的:观察八肽胆囊收缩素(CCK-8)对大鼠脊髓损伤后诱导型一氧化氮合酶(induciblenitricoxidesynthase,iNOS)表达的影响,进一步探讨CCK-8对脊髓损伤后的神经功能及其组织的保护作用。方法:实验于2003-09/2004-02在解放军总医院神经外科实验室进行。将36只SD大鼠随机分成3组,参照改良的Gruner法建立大鼠T9脊髓损伤模型,用免疫组化研究损伤后不同时间点iNOS的表达变化;选取3个表达最强时间点应用CCK-8腹腔内注射观察iNOS的表达变化。结果:正常脊髓组织内iNOS表达为(4.34±1.15)%,脊髓损伤后3d明显上升,7d表达最强,为(47.57±8.62)%,高于正常(P<0.01),14d时表达减弱;应用CCK-8后iNOS在7d时的表达明显减低为(30.50±5.17)%,与损伤组比差异有非常显著性意义(P<0.01)。结论:脊髓损伤后iNOS表达增高,与继发性的炎症反应相关;CCK-8能够抑制这种炎症反应,具有保护作用。

AIM: To observe the effect of cholecystokinin octapeptide (CCK- 8) on the expression of inducible nitricoxide synthase (iNOS) in rats with spinal cord injury (SCI), and study the protective role of CCK- 8 in neural function and tissue following SCI.METHODS:This experiment was completed from September 2003 to February 2004 in the Laboratory of Department of Neurosurgery, General Hospital of Chinese PLA. Thirty- six Sprague- Dawley rats were randomly divided into three groups. Rat SCI model(T9 segment) was established according to modified Gruner method,and immunohistochemistry was used to detect the activity of iNOS at different time points after SCI. The intraperitoneal injection of CCK- 8 was used to observe the expression change of iNOS at selected three time points in which the activity of iNOS was the most intensive. RESULTS: The activity of iNOS was(4.34± 1.15)% in uninjured spinal cord tissue. After SCI, the activity of iNOS was obviously increased at 3 days and reach to the peak at 7 days [(47.57± 8.62) % ] and decreased at 14 days,which was significantly higher than that of the normal group(P< 0.01).After intraperitoneal injection of CCK- 8, the expression of iNOS was decreased obviously at 7 days[(30.50± 5.17)% ],significantly lower than that of the SCI group(P< 0.01).CONCLUSION: Expression of iNOS after SCI is increased related to secondary inflammatory reaction,and CCK- 8 has the protective effect through inhibiting the inflammatory reaction.