CAJ | 학술논문

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。
목적：조직격태석방매대우당뇨병병발뇌졸중시부구유신경보호작용상미연구증실。관찰조직격태석방매대당뇨병대서국조성뇌결혈재관주적신경보호작용。방법선용건강웅성SD대서，경련뇨좌균소（ streptozotocin， STZ）복강주사유도위당뇨병대서。채용전선법제비국조성뇌결혈재관주모형，수궤수자표법분위3조：가수술조，등삼염수조화조직격태석방매조。24 h후관찰각조대서신경공능결손평분，측정뇌경사면적백분비화뇌수종정도。통과면역조화방법검측소효질세포리자개접두단백（ ionized calcium bindingadaptor molecule-1， Iba1）급수과양화물매（ myeloperoxidase， MPO）염색양성세포수，채용실시형광정량PCR기술검측결혈반암대구세포간점부분자-1（ intercellular adhesion molecule 1， ICAM-1）급혈관세포점부분자-1（vascular cell adhesion molecule 1， VCAM-1）적표체。결과조직격태석방매조교등삼염수조신경공능결손평분현저감경（P＜0．01），경사면적백분비명현축소[（23．57±5．79）％ vs （47．97±1．19）％，P＜0．01]，뇌수종정도현저강저[（81．73±2．10） vs （84．94±2．34）％，P＜0．05]，Iba1양성세포수명현감소[（12．33±4．46）개／HP vs （31．83±8．13）개／HP， P＜0．01]，MPO양성세포수명현감소[（13．83±4．49）개／HP vs （37．50±7．64）개／HP，P＜0．01]，ICAM-1급VCAM-1적표체수평균현저강저（ P＜0．05）。결론조직격태석방매통과억제국조성뇌결혈재관주손상인발적염증반응，대당뇨병대서뇌결혈재관주발휘신경보호작용。
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 Iba1-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 ±1.19]%, P<0.01), brain edema ([81.73 ±2.10] vs [84.94 ±2.34]%, P<0.05), the counts of Iba1-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.