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目的:明确乌司他丁(UTI)对小鼠脑缺血再灌注神经损伤的影响以及机制。方法:利用雄性C57BL/6小鼠,采用线栓法进行大脑中动脉阻塞(MCAO)60min,再灌注24h,建立脑缺血再灌注损伤模型。将小鼠随机分为4组:Sham(假手术)组、MCAO(MCAO+0.9%生理盐水)组、UTI治疗Ⅰ(MCAO+UTI 150U/10g)组和UTI治疗Ⅱ(MCAO+UTI 300U/10g)组,UTI在再灌注即刻、8h、16h和24h经腹腔给药。应用神经功能学评分、2,3,5-氯化三苯甲基四氮唑(TTC)染色、免疫荧光染色、酶联免疫吸附试验(ELISA)和Western-blot方法检测各组小鼠神经损伤情况、脑组织中肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、TLR-4(Toll-like receptors 4)和核因子-κB(NF-κB)的表达情况。结果:与MCAO组相比,UTI治疗Ⅰ组(P<0.05)和乌司他丁治疗Ⅱ组(P<0.01)小鼠脑缺血再灌注后神经损伤明显减轻,脑梗死容积缩小,炎性因子TNF-α、IL-6、TLR-4和NF-κB的表达受到抑制。结论:UTI对脑缺血再灌注具有神经保护作用,其机制可能是与降低TNF-α、IL-6、TLR-4和NF-κB介导的炎症反应有关。
Objective: To investigate the effect and mechanism of ulinastatin (UTI) on nerve injury induced by cerebral ischemia-reperfusion in mice. Methods: Male C57BL / 6 mice were subjected to occlusion of the middle cerebral artery (MCAO) for 60 min by thread occlusion and reperfusion for 24 h. The model of cerebral ischemia-reperfusion injury was established. The mice were randomly divided into 4 groups: sham group, MCAO group (MCAO + 0.9% saline), UTI group Ⅰ (MCAO + UTI 150U / 10g) and UTI group Ⅱ ) Group. UTI was administered intraperitoneally immediately after reperfusion, 8h, 16h and 24h. Neurological deficits in each group were evaluated by neurological score, TTC staining, immunofluorescence staining, ELISA and Western-blot. , The expression of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), TLR-4 and NF-κB in brain tissue. Results: Compared with MCAO group, the nerve injury in the UTI group was significantly reduced (P <0.05) and the ulinastatin group Ⅱ (P <0.01) The expression of TNF-α, IL-6, TLR-4 and NF-κB were inhibited. CONCLUSION: UTI has neuroprotective effect on cerebral ischemia-reperfusion. Its mechanism may be related to decreasing the inflammatory reaction mediated by TNF-α, IL-6, TLR-4 and NF-κB.