组织激肽释放酶对糖尿病大鼠局灶性脑缺血再灌注后炎症损伤的干预作用  

Protective effect of tissue kallikrein against inflammation following focal cerebral ischemia-reperfusion in diabetic rats

作　　者：石瑞峰[1] 刘玲[1] 胡斌[2] 陈昕[1] 曹琴琴[1] 赵玲玲[1] 张仁良[1] 

机构地区：[1]南京大学医学院附属金陵医院(南京军区南京总医院)神经内科,南京医学硕士210002 [2]马鞍山市人民医院骨科,马鞍山243000

出　　处：《医学研究生学报》2015年第9期904-909,共6页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81070923;81100870);江苏省自然科学基金(BK2011663;BK20141373)

摘　　要：目的组织激肽释放酶对于糖尿病并发脑卒中是否具有神经保护作用尚未研究证实。观察组织激肽释放酶对糖尿病大鼠局灶性脑缺血再灌注的神经保护作用。方法选用健康雄性SD大鼠,经链脲佐菌素(streptozotocin,STZ)腹腔注射诱导为糖尿病大鼠。采用栓线法制备局灶性脑缺血再灌注模型,随机数字表法分为3组:假手术组,等渗盐水组和组织激肽释放酶组。24 h后观察各组大鼠神经功能缺损评分,测定脑梗死面积百分比和脑水肿程度。通过免疫组化方法检测小胶质细胞离子钙接头蛋白(ionized calcium bindingadaptor molecule-1,Iba1)及髓过氧化物酶(myeloperoxidase,MPO)染色阳性细胞数,采用实时荧光定量PCR技术检测缺血半暗带区细胞间黏附分子-1(intercellular adhesion molecule 1,ICAM-1)及血管细胞黏附分子-1(vascular cell adhesion molecule 1,VCAM-1)的表达。结果组织激肽释放酶组较等渗盐水组神经功能缺损评分显著减轻(P<0.01),梗死面积百分比明显缩小[(23.57±5.79)%vs(47.97±1.19)%,P<0.01],脑水肿程度显著降低[(81.73±2.10)vs(84.94±2.34)%,P<0.05],Iba1阳性细胞数明显减少[(12.33±4.46)个/HP vs(31.83±8.13)个/HP,P<0.01],MPO阳性细胞数明显减少[(13.83±4.49)个/HP vs(37.50±7.64)个/HP,P<0.01],ICAM-1及VCAM-1的表达水平均显著降低(P<0.05)。结论组织激肽释放酶通过抑制局灶性脑缺血再灌注损伤引发的炎症反应,对糖尿病大鼠脑缺血再灌注发挥神经保护作用。Objective It remains to be confirmed whether tissue kallikrein has neuroprotective effect in diabetes-induced stroke. This study was to investigate the neuroprotection of tissue kallikrein against cerebral ischemia-reperfusion injury in diabetic rats. Methods Healthy male SD rats were randomly divided into a sham operation, a saline control, and a tissue kallikrein group. Diabetes mellitus was induced in the animals by intraperitoneal injection of streptozotocin and the model of focal cerebral ischemia-reperfusion was made with an intraluminal vascular occlusion method. At 24 hours after modeling, we obtained the neurological deficit score, in- farct size, and brain water content, counted Ibal- and MPO-positive cells by immunohistochemistry, and determined the expressions of ICAM-1 and VCAM-1 by real-time PCR. Results In comparison with the saline controls, the rats treated with tissue kallirein showed significant decreases in the neurological deficit score （P 〈 0.01 ）, the infarct size （[23.57 ±5.79] vs [47.97 ± 1. 191%, P〈0.01）, brain edema （[81.73 ±2.10] vs [84.94 ±2.34]%, P 〈 0.05）, the counts of Ibal- and MPO-positive cells （ 12.33 ± 4.46 vs 31.83 ± 8.13 and 13.83± 4.49 vs 37.50 ± 7.64, both P 〈 0.01 ）, and the expressions of ICAM-1 and VCAM-1 （ both P 〈 0.05 ）. Conclusion Tissue kallikrein has a neuroprotective effect against cerebral ischemia-reperfusion injury in diabetic rats, which may be associated with its anti-inflammation property.

关 键 词：组织激肽释放酶 糖尿病 脑缺血再灌注 小胶质细胞 中性粒细胞 细胞间黏附分子-1 血管细胞黏附分子-1 

分 类 号：R587.1[医药卫生—内分泌]