辛伐他汀对新生鼠脑缺氧缺血后海马区一氧化氮合酶的影响

目的探讨新生大鼠缺氧缺血脑损伤(HIBD)后海马区各型一氧化氮合酶(NOS)活性的变化及辛伐他汀对其的调节作用。方法选用7日龄SD大鼠,随机分组、建立新生大鼠HIBD模型后,于不同时间点剥取脑海马,测定各型NOS的变化并比较各组之间的差别。结果HIBD后生理盐水组诱导型NOS(iNOS)活力水平于12h时始显著增高,48h达高峰,7d时接近假手术组水平(P>0.05),12h、24h、48h、72h时胞二磷胆碱组、辛伐他汀组明显低于生理盐水组,72h时,辛伐他汀组显著低于胞二磷胆碱组(P<0.01)。生理盐水组结构型NOS(cNOS)水平于0h即显著升高,然后逐渐下降,72h时接近假手术组水平,而胞二磷胆碱组、辛伐他汀组仍继续增高,48h达高峰,但辛伐他汀组升高更显著。结论各型NOS均参与了HIBD的发病过程,辛伐他汀和胞二磷胆碱对新生大鼠HIBD的保护作用与其调节NOS有关,且辛伐他汀的作用更强。

Effects of simvastatin on the isforms of nitric oxide synthase in hippocampus of neonatal brain after hypoxic-ischemic damage in rats.

Objective To study the changes of various isoforms of nitric oxide synthases(NOS) in hippocampus of neonatal rats after hypoxic-ischemic brain damage(HIBD) and the modulation effect of simvastatin on them. Methods One hundred and forty-four SD rats of 7-day-old were randomly divided into four groups, i.e. sham operation group(sham group), normal saline control group(saline group), citicoline control group(CDPC group) and simvastatin treated group. Each group was divided into six subgroups according to various intervals of taking rats' brain tissue(0 h , 12 h , 24 h , 48 h , 72 h and 7 d after HIBD or sham operation). Rats were administered intraabdominally with 10 ml/kg diluted citicoline or 20 mg/kg of activated simvastatin or a equivalent volume of NS once daily immediately after HIBD.Carotid arteries of animals of sham group were only isolated but not ligated and these animals did not experience hypoxia or receive medicine. The activities of NOS were examined by spectroscopy in hippocampus of neonatal rats at different intervals after HIBD or sham operation and the differences among them were compared. Results The activity of inducible NOS(iNOS) increased significantly 12 h after HIBD, peaked at 48 h, then decreased gradually and reached to the level as that in sham group over 7 days(P>0.05). Simvastatin and citicoline both downregulated remarkably the activity of iNOS at 12 hs, 24 hs ,48 hs and 72 hs, but simvastatin downregulated it greatly more than citicoline did at 72 hs(P<0.01). The activities of constitutive NOS(cNOS) rised greatly at 0 h after HIBD, then declined slowly and there was no remarkable difference between saline group and sham group at 48 hs. Compared with saline group, the activities of cNOS either in CDPC group or in simvastatin group were greatly lower at 0 h, almost the same at 12 hs, and remarkable higher at 24 hs, 48 hs and 72 hs, but the activities of cNOS of simvastatin group were significantly higher than that of CDPC group at 48 hs and 72 hs. Conclusions The different isoforms of NOS may play a role in the pathogenesis of HIBD, the protective mechanisms of simvastatin and citicoline are associated with their modulations on them, and simvastatin is superior to citicoline.