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机制探讨  

Protection by urokallikrein against focal cerebral ischemia in rats with type 2 diabetes mellitus and its mechanism

作　　者：宋晓伟[1] 闵连秋[1] 张昊 韩苗苗[1] 

机构地区：[1]辽宁医学院附属第一医院神经内科,锦州121001 [2]山东省济宁市微山县人民医院急诊科,济宁277605

出　　处：《中国新药杂志》2009年第7期641-645,共5页Chinese Journal of New Drugs

基　　金：辽宁省教育厅高等学校科学研究计划(05L137)

摘　　要：目的:探讨尤瑞克林对2型糖尿病局灶性脑缺血大鼠的神经保护作用及其可能的机制。方法:制备2型糖尿病大鼠局灶性脑缺血模型,尤瑞克林低、中、高剂量组于造模后30 m in舌下静脉一次性注射尤瑞克林3.50×10-3,8.75×10-3和17.5×10-3PNAU.kg-1,24 h后行神经行为学评分和HE染色,免疫组化SABC染色法测定诱导型一氧化氮合酶(iNOS)的含量。实验另设正常大鼠单纯缺血组、模型组,每组12只大鼠。结果:与正常大鼠单纯缺血组比较,2型糖尿病局灶性缺血模型组大鼠神经行为学评分明显升高(P<0.01),HE染色神经细胞受损明显(P<0.01),脑组织海马iNOS活性明显降低(P<0.01)。与模型组比较,尤瑞克林低、中、高剂量组均不同程度降低神经行为学评分及iNOS活性(P<0.01),改善神经细胞的受损程度(P<0.01),其中以中、高剂量组明显(P<0.05),但中、高剂量组间无明显差异(P>0.05)。结论:2型糖尿病能加重缺血性脑损伤的程度,尤瑞克林对2型糖尿病局灶性脑缺血大鼠具有神经保护作用,其机制可能与降低iNOS的活性,减少神经毒性NO的含量有关。Objective： To investigate the neuroprotective effect of urokallikrein on ischemie brain injury in rats with type 2 diabetes mellitus. Methods： In SD rats with type 2 diabetes mellitus, urokallikrein at doses of 3.75, 8.75 and 17.25 PNAU.kg^-1 was injected 30 min following middle cerebral artery occlusion. The neurological function was evaluated, the pathological change was observed after HE staining, and the expression of iNOS was detected by SABC immunohistochemica method 24 h after middle cerebral artery occlusion. The rats with focal cerebral ischemia but without diabetes were used as a control. For each group, 12 rats were used. Results： Compared with focal cerebral ischemia in rats without diabetes, the neurological function score was increased, cell injury （ HE staining） was more severe, and the number of the positive iNOS cells was increased in the hippocampus after ischemia in diabetic rats; the difference between the two groups was significant（P 〈 0.01 ）. Compared with ischemic control, urokallikrein reduced neurological function score, attenuated cell injury, and reduced the number of iNOS- positive cells. The two higher doses were more effective than the lower dose （P 〈 0.05） , but were not difference between them （ P 〉 0.05 ）. Conclusion ： The ischemic brain injury can be aggravated in rats with type 2 diabetes mellitus. Urokallikrein has neuroprotective effect on focal cerebral isehemia in SD rats with type 2 diabetes mellitus, its mechanism may relate to reduction of iNOS activity.

关 键 词：尤瑞克林 糖尿病 局灶性脑缺血 诱导型一氧化氮合酶 

分 类 号：R743.31[医药卫生—神经病学与精神病学] R965.1[医药卫生—临床医学]