论文部分内容阅读
目的探讨组蛋白去乙酰化酶6(HDAC6)在小鼠脑出血后神经元凋亡中的作用及潜在机制。方法将C57BL/6小鼠随机分为假手术组、脑出血组和HDAC6抑制剂Tubastatin A(Tub A)治疗组(Tub A 10 mg·kg-1治疗组和Tub A30mg·kg-1治疗组)。采用自体血注射法构建小鼠脑出血模型。采用改良神经功能缺损评分(m NSS)量表进行神经功能损伤评分,干湿比重法测量脑水肿含量,免疫荧光染色检测神经元凋亡情况,应用Western blot法分别检测HDAC6、激活型半胱氨酸蛋白酶-3、Bax和Bcl-2蛋白的表达。结果脑出血后,HDAC6的表达明显升高,Tub A能显著降低神经功能缺损评分,减轻脑组织水肿程度,减少神经元凋亡数量,增加Bcl-2蛋白表达,抑制激活型半胱氨酸蛋白酶-3和Bax蛋白表达。结论小鼠脑出血后,Tub A特异性抑制HDAC6活性可上调Bcl-2,降低Bax和激活型半胱氨酸蛋白酶-3的表达,减少神经元凋亡,从而改善脑出血模型小鼠的神经功能缺损症状。
Objective To investigate the role of histone deacetylase 6 (HDAC6) in neuronal apoptosis after intracerebral hemorrhage in mice and its potential mechanism. Methods C57BL / 6 mice were randomly divided into sham operation group, intracerebral hemorrhage group and HDAC6 inhibitor Tubastatin A (Tub A) treatment group (Tub A 10 mg · kg -1 treatment group and Tub A30 mg · kg -1 treatment group) . The model of intracerebral hemorrhage in mice was established by autologous blood injection. Neurological impairment scores were measured by using modified neurological deficit score (mNSS) scale, brain edema content was measured by wet-dry proportioning method, neuron apoptosis was detected by immunofluorescence staining, Western blot was used to detect HDAC6, activated cysteamine Acid protease-3, Bax and Bcl-2 protein expression. Results After intracerebral hemorrhage, the expression of HDAC6 was significantly increased. Tub A significantly reduced the neurological deficit score, reduced the degree of edema in brain tissue, decreased the number of neuronal apoptosis, increased the expression of Bcl-2, and inhibited the activation of caspase -3 and Bax protein expression. CONCLUSION Tubal-specific inhibition of HDAC6 activity can up-regulate Bcl-2, decrease the expression of Bax and activin-like caspase-3 and decrease neuronal apoptosis after ICH in mice Symptoms of functional impairment.