尤瑞克林对2型糖尿病大鼠局灶性脑缺血的神经保护作用

Protective effects of urokallikrein on type 2 diabetes mellitus rats with focal cerebral ischemia

目的探讨尤瑞克林对2型糖尿病大鼠局灶性脑缺血的神经保护作用及其可能的机制。方法选用健康雄性SD大鼠,随机分为单纯缺血组,糖尿病缺血组,尤瑞克林低、中、高3个剂量组,每组12只。制作2型糖尿病大鼠局灶性脑缺血模型,术后30min尤瑞克林低、中、高剂量组舌下静脉注射尤瑞克林3.50×10-3、8.75×10-3、17.5×10-3PNA单位·kg-1,余各组以同样给药途径予等剂量生理盐水。行神经行为学评分,检测大鼠缺血侧海马组织含水量及一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)的含量。结果与单纯缺血组比较,糖尿病缺血组大鼠海马组织NO含量及iNOS活性增高,神经行为学评分明显升高(P<0.01),HE染色示神经细胞受损明显;与糖尿病缺血组比较,尤瑞克林低、中、高剂量组NO含量、iNOS活性和神经行为学评分均不同程度降低(P<0.05),神经细胞受损程度改善,其中中、高剂量组较低剂量组作用更明显(P<0.05),但中、高剂量组间无明显差异(P>0.05)。结论高血糖可加重脑缺血损伤,尤瑞克林可能通过降低iNOS的活性、减少神经毒性NO的产生,对2型糖尿病局灶性脑缺血起到神经保护作用。

AIM To investigate the neuro-protective effects and probable mechanism of urokallikrein on type 2 diabetes mellitus Sprague-Dawley （SD） rats with focal cerebral ischemia. METHODS The healthy SD rats were randomly divided into 5 groups： simple focal cerebral ischemia group, diabetes mellitus with cerebral ischemia group, urokallikrein group including 3 doses （3.75, 8.75, 17.25 PNA U·kg^-1 30 min after operation） , other groups given physiological saline by the same route of administration. The neurological function, contents of nitric oxide （NO） and expression of inducible nitric oxide synthase （iNOS） in hippocampal tissue were observed. RESULTS Comparing with rats in simple focal cerebral ischemia group, the amount of NO, the activity of iNOS in hippocampus and the neurological function score of diabetes mellitus with cerebral ischemia group increased, with significant difference （P 〈 0.01 ） ; HE stain showed obvious damage of neural cells. Comparing with rats in diabetes mellitus with cerebral ischemia group, the contents of NO and the activity of iNOS were lower in each urokallikrein group, with improved neurological function （P 〈 0.05） , especially in medium-dose and high-dose groups （P 〈 0.01） , but there was no significant difference between medium-dose and high-dose groups （P 〉 0.05）. CONCLUSION Hyperglycemia can aggravate cerebral ischemic damage and urokallikrein provide neuro-protective for type 2 diabetes mellitus with focal cerebral ischemia probably through lowing the activity of iNOS and neuro-toxic produced by NO.