罗格列酮对实验性大鼠脑出血后细胞凋亡的影响

The effect of rosiglitazone on neuron apoptosis after intracerebral hemorrhage in rats

目的:探讨罗格列酮对大鼠脑出血(intracerebral hemorrhage,ICH)后血肿周围脑组织细胞凋亡的影响。方法:88只健康老龄雄性SD大鼠,随机分为假手术组8只,模型组40只,罗格列酮干预组40只,后2组又分为6 h、12 h、24 h、72 h、7 d 5个亚组,每组8只。采用大鼠股动脉新鲜自体不凝血50μl注入大脑纹状体基底节区复制脑出血模型,干湿重法检测脑组织含水量(water content of brain,BWC);原位末端标记法(TUNEL)检测大鼠脑细胞的凋亡情况;免疫组化法检测过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptors gamma,PPARγ)和半胱氨酸蛋白-3(Caspase-3)的表达情况。结果:(1)随着大鼠脑出血后时间的延长,ICH组BWC呈逐渐增高趋势,并在72 h达高峰。与模型组比较,罗格列酮干预组BWC均降低,组织水肿减轻(P<0.05)。TUNEL染色结果显示凋亡细胞的数量与各位BWC的复化相一致。(2)免疫组化法检测结果显示:大鼠脑出血后72 h,Caspase-3凋亡相关蛋白的表达明显上调。罗格列酮干预后,与模型组相比,PPARγ高表达,同时Caspase-3表达和凋亡细胞数明显降低,差异有统计学意义(P<0.05或P<0.01)。结论:PPARγ激动剂罗格列酮可能通过抑制Caspase-3的表达,降低脑出血后脑组织的继发性凋亡损伤,对脑组织起保护作用。

Objective： To evaluate the effect of rosiglitazone（ RSG） on neuron apoptosis after intracerebral hemorrhage（ ICH） in rats. Methods： Eighty-eight healthy Sprague-Dawley rats were randomly divided into sham group（ n = 8）,ICH group（ n = 40） and RSG treatment group（ n = 40）. The later two groups were randomly divided into 5 subgroups respectively： 6,12,24,72 h and 7 d groups after ICH,and 8 rats in each group. ICH models were established by injecting 50 μl of autogenous blood from the femoral artery into the right striatum basal of rats. The water content of brain（ BWC） was checked up with dry/wet weight method,the apoptotic cells were detected with TUNEL,the expression of protein of both peroxisome proliferators-activated receptors gamma（ PPARγ） and Caspase-3 was determined by immunohistochemistry. Results：（ 1） The water content of brain（ BWC） following time prolong of intracerebral hemorrhage was gradually increased in ICH group and reached the peak at 72 h. After RSG treatment,the BWC was significantly decreased and the tissue edema was reduced in RSG group than those in sham group（ P 〈 0. 01）. TUNEL staining results showed that there was positive correlation between the numbers of apoptotic cells with the change of BWC in each group.（ 2） The immunohistochemical staining results showed that the expression of Caspase-3 after intracerebral hemorrhage 72 h was significantly increased. After RSG treatment,the expression of PPARγ was increased,while the expression of Caspase-3 and the number of apoptotic cells was both significantly decreased in RSG group than those in sham group（ P 〈0. 05 or P 〈 0. 01）. Conclusion： After intracerebral hemorrhage,RSG with activation of PPARγ can reduced secondary apoptotic of ICH by inhibiting expression of Caspase-3,which protected intracerebral hemorrhage injury.