赖诺普利对糖尿病大鼠周围神经微循环的影响  

Effects of lisinopril on microcirculation of diabetic peripheral nerve in rats

作　　者：韩丽萍[1] 谢云[1] 李春君[1] 管乐[1] 马泽军[1] 陈莉明[1] 

机构地区：[1]天津医科大学代谢病医院神经内科卫生部激素与发育重点实验室,300070

出　　处：《中华糖尿病杂志》2014年第4期229-233,共5页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的 观察赖诺普利对糖尿病大鼠周围神经微循环的改善及对神经组织功能和结构的影响.方法 将25只约6周龄健康雄性Wistar大鼠以链脲佐菌素（STZ）尾静脉注射制备糖尿病大鼠模型,成模后按随机数字表法分为糖尿病组（n=8）和赖诺普利治疗组（n=8,20 mg· kg-1 ·d-1,8周）,8只健康大鼠作为正常对照.8周后,观察各组大鼠坐骨神经传导速度及超微结构的改变.采用化学比色法测定血浆一氧化氮（NO）,神经组织氧化应激指标超氧化物歧化酶（SOD）、丙二醛（MDA）水平,放射免疫法测定血浆前列环素（6-keto-PGF1 α）含量,酶联免疫吸附法（ELISA）测定血浆纤溶酶原激活物抑制物（PAI-1）、组织型纤溶酶原激活物（t-PA）水平,CD34免疫组化法测定坐骨神经内膜毛细血管密度.采用单因素方差分析进行多组间均数比较.结果 与正常对照组相比,糖尿病大鼠出现坐骨神经运动和感觉神经传导速度减慢（t=8.952、9.642,均P＜0.05）和超微结构异常,伴有血浆NO、6-keto-PGFlα、t-PA、SOD水平降低,PAI-1及MDA水平升高（t=3.535～8.054,均P＜0.05）.赖诺普利治疗组坐骨神经运动和感觉神经传导速度均较糖尿病组显著提高（t=6.774、7.058,均P＜0.05）,电镜显示赖诺普利治疗组坐骨神经轴突和髓鞘萎缩、变性及毛细血管狭窄、闭塞等病理损伤明显减轻.与糖尿病组相比,赖诺普利治疗组血浆NO、6-keto-PGF1 α、t-PA、SOD显著升高而PAI-1、MDA明显降低（t=2.611 ～6.544,均P＜0.05）,促进神经内膜血管新生（t=6.868,P＜0.05）.结论 赖诺普利可能通过改善微循环异常,增加周围神经血流灌注量,对早期糖尿病周围神经病变起保护作用.Objective To investigate the impacts of lisinopril on the microcirculation of peripheral nerve as well as nerve function and structure in diabetic rats.Methods Diabetic rat model was prepared by injecting streptozotocin into the tail veins of 25 six-week-old healthy male Wistar rats.The rats models were randomly divided into diabetic group and lisinopril treatment group （20 mg · kg-1 · d-1,8 weeks）,10 healthy rats were set as normal controls.Sciatic nerve conduction velocity and ultrastructure were observed 8 weeks after intervene.The plasma nitric oxide （NO）,nerve tissue superoxide dismutase （SOD）,malondialdehyde （MDA） levels by were detected by chemocolorimetry.The 6-keto-prostaglandin F1α （6-keto-PGF1 α） levels were measured by radioimmunoassay,and plasminogen activator inhibitor（PAI-1）,tissuc-typc plasminogen activator （t-PA） were assayed by enzyme linked immunosorbent assay （ELISA）,capillary density of sciatic endoneurium was evaluated by immunohistochemistry of CD34.Single factor analysis of variance was used to compare the differences among groups.Results Compared with those in normal control group,the motor and sensory nerve conduction velocity of diabetic rats slowed down （t =8.952,9.642,both P ＜ 0.05） and the ultrastructure of the sciatic nerve was abnormal; Plasma NO,6-keto-PGF1α,t-PA,SOD levels decreased and PAI-1,MDA increased in diabetic rats（t =3.535-8.054,all P ＜0.05）.The motor and sensory nerve conduction velocity of sciatic nerve in lisinopril treatment group improved significantly than those in diabetic rats （t =6.774,7.058,both P ＜ 0.05）,and the extenuated atrophy and degeneration of axon and myelin,and ameliorated stenosis and occlusion of capillary of sciatic nerve were all improved.Moreover,the plasma levels of NO,6-keto-PGFlα,t-PA and SOD levels increased and PAL1 and MDA levels decreased significantly in lisinopril treatment group than those in diabetic rats （t =2.611-6.544,all P ＜ 0.05）,and the angiogenesis of endoneurium was

关 键 词：糖尿病 周围神经系统疾病 赖诺普利 微循环 血管新生 

分 类 号：R587.2[医药卫生—内分泌]