右美托咪定对痫性发作大鼠海马神经细胞B细胞淋巴瘤／白血病-2、B细胞淋巴瘤／白血病-2相关X蛋白、半胱氨酰天冬氨酸特异性蛋白酶-3蛋白表达的影响

Effect of dexmedetomidine on apoptotic protein expression about B cell lymphoma/lewkmia - 2, B cell lymphoma/lewkmia -2 associated X protein, Caspase -3 in hippocampal neurons of epileptic rats

目的观察右美托咪定（DEX）对痫性发作大鼠海马神经细胞凋亡蛋白表达的影响。方法将36只sD大鼠随机分为3组（n=12）：对照组（Control组）、右美托咪定组（DEX组）及致痫组（EP组）。DEX组给予10μg／k剂量DEX灌胃，连续3d，至致痫当日；对照组、致痫组则分别给予等体积生理盐水灌胃。以氯化锂-匹罗卡品制作致痫模型，观察SD大鼠行为学变化；采用Westernblot检测B细胞淋巴瘤／白血病-2（bcl-2）、bcl-2相关x蛋白（bax）和半胱氨酰天冬氨酸特异性蛋白酶-3（Caspase-3）表达水平。结果EP组大鼠均表现易激惹，DEX组反复自发性痫性发作（SRS）次数[（5．67±1．53）次]比EP组[（10．33±3．06）次]明显减少，且差异有统计学意义（P〈0．05）。bcl-2、bax、bcl-2／bax和Caspase-3表达水平结果，对照组分别为1．0557±0．0081、0．5712±0．0057、1，0870±0．0026、0；DEX组分另U为0．9654±0．0216、0．6920±0．0028、1．3951±0．0328、0．6765±0．9697；EP组分另0为0．8925±0．0063、0．7427±0．0010、1．2016±0．0082、0．8565±0．9626。EP组与对照组比较，大鼠海马、bax、活化的active—Caspase-3表达水平增加，bcl-2表达水平降低，差异有统计学意义（P〈0．05），bcl-2／bax比值升高，差异有统计学意义（P〈0．05）；DEX组与EP组比较，海马bcl-2表达水平、bcl-2／bax比值升高，bax、active—Caspase-3表达水平降低，差异有统计学意义（P〈0．05）。结论DEX可能作用抑制大鼠海马神经细胞Casepase-3和box基因表达，减少SRS次数，对海马神经元产生保护作用。

Objective To observe the effect of dexmedetomidine （DEX） on apoptotic protein ex- pression in hippocampal neurons of epileptic rats. Methods Thirty - six SD rats were randomly divided in- to 3 groups （n = 12） ： control group, DEX group and epilepsy （EP） group. The DEX Group was given ga- vage administration of DEX （ 10 μg/kg） for 3 consecutive days until the date of epilepsy seizure. The con- trol group and EP group were given gavage administration of the same volume of normal saline. Lithium chloride -pilocarpine was used to establish epileptogenic model to observe the behavioral changes of SD rats. Western blotting was adopted to detect the expression level of B cell lymphoma/lewkmia -2 （ bcl - 2）, bcl - 2 associated X protein （bax） and cysteinyl aspartate specific proteinase - 3 （ Caspase - 3 ）. Results Unexceptionally all the rats in EP group showed irritability. The recurrent spontaneous seizures （SRS） counts in DEX group （5.67 ±1.53 ） were significantly reduced as compared with EP group （ 10. 33 ±3.06） （ P 〈 0.05 ）. The expression levels of bcl - 2, bax, bcl - 2/bax ratio and Caspase - 3 in control group were 1. 055 7±0. 008 1,0. 571 2 ±0. 005 7,1. 087 0±0. 002 6 and 0, those in DEX group were 0. 965 4 ±0. 021 6,0. 692 0 ±0. 002 8,1. 395 1 ±0. 032 8 and 0. 676 5 ±0. 969 7, and those in EP group were 0. 892 5 ± 0. 006 3,0. 742 7± 0. 001 0,1. 201 6±0. 008 2 and 0. 856 5 ± 0. 962 6, respeclively. As compared with control group, bax and active - Caspase -3 in the EP group were increased in the hippocampus of rats, and bcl - 2 expression level was significantly reduced statistically （ P 〈 0. 05 ）. The bcl - 2/bax ratio was increased statistically （ P 〈 0. 05 ）. As compared with EP group, bcl - 2 expression level and bcl - 2/bax ratio were increased, and the expression levels of bax and active - Caspase - 3 were reduced in the hippocampus of DEX group. （P 〈 0. 05 ）. Conclusion DEX may play a role in inhibiting the gene expression path of Caspase -3 and bax in rat hippocampal neurons and reducing the SRS counts. So it will protect the hippocampal neurons.