【摘要】 目的 探究阿托伐他汀对高血糖诱导的小鼠脑缺血后出血转化(HT)的作用及机制。方法 36只SPF级雄性C57BL/6小鼠随机分为假手术组、HT模型组和阿托伐他汀组，每组12只。比较各组小鼠神经功能评分、死亡率、HT发生率、HT分级评分，苏木精-伊红染色观察脑组织出血情况，免疫荧光染色评估血脑屏障通透性，Western blot检测缺血半暗带脑组织免疫球蛋白G(IgG)、闭锁连接蛋白1(ZO-1)、闭合蛋白(occludin)、紧密连接蛋白5(claudin5)、基质金属蛋白酶(MMP)2和MMP-9的蛋白表达。结果 与假手术组比较，HT模型组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度、IgG、MMP-2、MMP-9蛋白表达水平显著增高，ZO-1、occludin、claudin5蛋白表达水平明显降低(P<0.01)。与HT模型组比较，阿托伐他汀组神经功能评分、死亡率、HT发生率、HT评分、IgG荧光强度及IgG、MMP-2、MMP-9蛋白表达水平显著降低[(2.73±1.19)分vs(3.91±0.94)分，16.7%vs 41.6%,58.3%vs 91.6%,(1.00±1.04)分vs(2.58±1.13)分，(504.30±105.52)a.u vs(859.91±153.28)a.u, 4.55±1.40 vs 12.06±3.73,1.87±0.41 vs 2.95±0.68,1.47±0.24 vs 2.12±0.23,P<0.05,P<0.01],ZO-1、occludin、claduin5蛋白表达显著升高(1.55±0.20 vs 0.53±0.10,0.92±0.11 vs 0.35±0.07、0.58±0.04 vs 0.30±0.05,P<0.01)。结论 阿托伐他汀可通过抑制MMP-2、MMP-9激活，上调ZO-1、occludin、claudin5表达，降低血脑屏障通透性，从而抑制高血糖诱导的脑缺血后HT。更多还原

【Abstract】 Objective To investigate the role and underlying mechanism of atorvastatin on hyperglycemia induced hemorrhagic transformation(HT) in a mouse model of cerebral ischemia.Methods A total of 36 SPF-grade male C57BL/6 mice were randomly divided into sham operation group, HT model group and atorvastatin group, with 12 mice in each group.HE staining was used to observe cerebral hemorrhage, immunofluorescent staining was employed to detect the integrity of blood-brain barrier, and Western blotting was applied to measure the protein expression of IgG,ZO-1,occludin, claduin5,MMP-2 and-9 in ischemic penumbra brain tissues.Results Compared with sham operation group, the neurological deficit score, mortality rate, HT incidence, HT grading score, IgG fluorescence intensity, and protein levels of IgG,MMP-2 and-9 were significantly increased, while the protein levels of ZO-1,occludin and claudin5 were obviously decreased in the HT model group(P<0.01).Atorvastatin treatment resulted in significantly lower neurological deficit score(2.73±1.19 vs 3.91±0.94),mortality rate(16.7% vs 41.6%),HT incidence(58.3% vs 91.6%),HT grading score(1.00±1.04 vs 2.58±1.13),IgG fluorescence intensity(504.30±105.52 a.u vs 859.91±153.28 a.u),and protein levels of IgG(4.55±1.40 vs 12.06±3.73),MMP-2(1.87±0.41 vs 2.95±0.68) and-9(1.47±0.24 vs 2.12±0.23)(P<0.05,P<0.01),and increased protein levels of ZO-1(1.55±0.20 vs 0.53±0.10),occludin(0.92±0.11 vs 0.35±0.07) and claudin5(0.58±0.04 vs 0.30±0.05)(P<0.01) when compared with the HT model group.Conclusion Atorvastatin can reduce the permeability of blood-brain barrier by inhibiting the activation of MMP-2 and MMP-9 and up-regulating the protein levels of ZO-1,occludin and claudin5,and thus attenuate hyperglycemia-induced HT.更多还原