【摘要】 目的 基于乙醛脱氢酶2(ALDH2)变化探讨尤瑞克林对糖尿病合并脑缺血再灌注大鼠神经元损伤的影响。方法 选取60只SPF级SD大鼠，使用体质量编号和随机数表法分为对照组、模型组、尤瑞克林组、尤瑞克林+氨基氰（Cya）组，使用无菌链脲佐菌素（STZ）联合Zea-Longa法制备糖尿病合并脑缺血再灌注大鼠模型，各组大鼠缺血再灌注24 h，评估神经功能评分、检测脑含水量，HE染色观察脑组织病理情况，TUNEL检测脑组织凋亡情况，Western blot法检测脑组织中活化半胱氨酸天冬氨酸蛋白酶-3(Cleaved caspase-3)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关x蛋白（Bax）、ALDH2蛋白表达情况，使用酶联免疫吸附法检测脑组织中的超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、丙二醛（MDA）、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)水平。结果 模型组大鼠的神经功能评分、脑含水量、细胞凋亡率、Cleaved caspase-3蛋白表达和MDA、TNF-α、IL-6、IL-1β水平均高于对照组（P<0.05），而Bcl-2/Bax、ALDH2蛋白表达和SOD、CAT活性均低于对照组（P<0.05）。尤瑞克林组、尤瑞克林+Cya组大鼠的神经功能评分、脑含水量、细胞凋亡率、Cleaved caspase-3蛋白表达和MDA、TNF-α、IL-6、IL-1β水平均低于模型组（P<0.05），而Bcl-2/Bax、ALDH2蛋白表达和SOD、CAT活性均高于模型组（P<0.05）。尤瑞克林+Cya组大鼠的神经功能评分、脑含水量、细胞凋亡率、Cleaved-caspase-3蛋白表达和MDA、TNF-α、IL-6、IL-1β水平均高于尤瑞克林组（P<0.05），而Bcl-2/Bax、ALDH2蛋白表达和SOD、CAT活性均低于尤瑞克林组（P<0.05）。结论 尤瑞克林可降低糖尿病合并脑缺血再灌注大鼠神经损伤、氧化应激和炎症反应，可能与提高ALDH2表达有关。更多还原

【Abstract】 Objective To explore the effects of urinary kallindinogenase on neuron damage in rats with diabetes mellitus combined with cerebral ischemia reperfusion based on the changes of acetal dehyde dehydrogenase 2(ALDH2). Methods A total of 60 SPF-level SD rats were enrolled and divided into control group, model group,urinary kallindinogenase group and urinary kallindinogenase+cyanamide(Cya) group by weight numbering method and random number table method. The models of rats with diabetes mellitus and ischemic brain injury were prepared by sterile streptozocin(STZ) combined with Zea-Longa method. After 24 h of ischemia reperfusion,scores of nerve function were evaluated. The water content in brain was detected. The pathology conditions of brain tissues were observed by HE staining. The apoptosis of brain tissues was detected by TUNEL. The expressions of cleaved cysteine proteinase-3(Cleaved caspase-3), B-cell lymphoma-2(Bcl-2), Bcl-2 associated x protein(Bax) and ALDH2 proteins in brain tissues were detected by Western blot. The levels of superoxide dismutase(SOD), catalase(CAT), malondialdehyde(MDA), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β) in brain tissues were detected by enzyme-linked immunosorbent assay. Results The scores of nerve function, water content in brain, apoptosis rate, expression of Cleaved-caspase-3 protein and levels of MDA, TNF-α, IL-6 and IL-1β in model group were higher than those in control group(P<0.05), while expressions of Bcl-2/Bax and ALDH2 proteins, activities of SOD and CAT were lower than those in control group(P<0.05). The scores of nerve function, water content in brain, apoptosis rate, expression of Cleaved caspase-3protein and levels of MDA, TNF-α, IL-6 and IL-1β in urinary kallindinogenase group and urinary kallindinogenase+Cya group were lower than those in model group(P<0.05), while expressions of Bcl-2/Bax and ALDH2 proteins,activities of SOD and CAT were higher than those in model group(P<0.05). The scores of nerve function, water content in brain, apoptosis rate, expression of Cleaved caspase-3 protein and levels of MDA, TNF-α, IL-6 and IL-1β in urinary kallindinogenase+Cya group were higher than those in urinary kallindinogenase group(P<0.05),while expressions of Bcl-2/Bax and ALDH2 proteins, activities of SOD and CAT were lower than those in urinary kallindinogenase group(P<0.05). Conclusion The urinary kallindinogenase can reduce nerve damage, oxidative stress and inflammation response in rats with diabetes mellitus and cerebral ischemia reperfusion, which may be related to increasing ALDH2 expression.更多还原