消栓肠溶胶囊对慢性脑低灌注大鼠皮层神经元损伤的影响

Effects of Xiaoshuan enteric-coated capsule on neuronal damage in cortex of cerebral hypo-perfusion rats

目的观察消栓肠溶胶囊对慢性脑低灌注大鼠皮层神经元损伤的影响。方法采用随机数字表完全随机化将大鼠分为假手术组12只，模型组17只，消栓肠溶胶囊大、中、小剂量组各15只。采用双侧颈总动脉永久性结扎（2VO）法制备大鼠慢性脑低灌注模型。造模后2h开始灌胃给药，消栓肠溶胶囊大、中、小剂量组分别灌胃消栓肠溶胶囊混悬液420、140、47mg／kg，假手术组、模型组灌胃等体积生理盐水。1次／d，连续给药40d后取材。采用免疫荧光染色法检测皮层神经元特异性核蛋白（NeuN）、半胱氨酸天冬氨酸蛋白酶-3（Caspase-3）表达。采用生化法检测皮层组织GSH．PX、SOD及MDA水平。结果与模型组比较，消栓肠溶胶囊大、中剂量组大鼠皮层神经元NeuN阳性表达[（8716．86±2539．93）、（9549．31±1663．26）比（7297．05±1932．49）]增强（P〈0．05或P〈0．01）、OSH-PX水平[（7．37±1．08）U／mg、（7．77±3．26）U／mg比（3．67±2．52）U／mg]升高（P〈0．05）；消栓肠溶胶囊大、中、小剂量组大鼠皮层Caspase-3阳性细胞数[（11．65±2．68）个／mm2、（14．05±4．55）个／mm2、（12．60±4．56）个，mm2比（16．80±5．41）个／mm2]减少（P〈0．05或P〈0．01）、皮层组织MDA水平[（1．44±0．40）nmol／mg、（1．96±1．13）nmol／mg、（2．12±1．19）nmol／mg比（3．19±0．98）nmol／mg]降低（P〈0．05或P〈0．01），SOD水平[（555．61±92．45）U／mg、（607．90±228．45）U／mg、（515．98±184．01）U／mg比（348．12±108．84）U／nag]升高（P〈0．05或P〈0．01）。结论消栓肠溶胶囊减轻慢低脑灌注引起的神经元损伤与改善脑组织自由基代谢关系密切。

Objective To observe the influence of Xiaoshuan enteric-coated Capsule （XSECC） on neuronal damage in cortex of cerebral hypo-perfusion rats. Methods Rats were divided into a sham group （12）, a model group （17）, a XSECC large dose group （15）, a medium dose group （15） and a low dose group （15） by a random number table. The cerebral hypo-perfusion model was produced by permanent bilateral common carotid artery ligation （2VO）. The mixed suspension of XSECC was given orally to rats in the XSECC large dose group （420 mg/kg）, the medium dose group （140 mg/kg） and the low dose group （47 mg/kg） once each day for 40 days from the beginning of two hour after ischemia. The expressions of NeuN and Caspase-3 were observed by immtmofluorescence staining at 40 days after ischemia. The content of GSH-PX, SOD and MDA were measured by biochemical assay. Results Compared to the model group, the expressions of NeuN （8 716.86 ± 2 539.93, 9 549.31 ± 1 663.26 vs. 7 297.05 ± 1 932.49） were significantly increased in the XSECC large dose group and the medium dose group （P〈0.05 or P〈0.01）; The content of GSH-PX （7.37 ± 1.08 U/mg, 7.77 ± 3.26 U/mg vs. 3.67 ± 2.52 U/mg） was increased in the XSECC large dose group and the medium dose group（P〈0.05）; The expressions of Caspase-3 （11.65 ± 2.68, 14.05 ± 4.55, 12.60 ± 4.56 vs. 16.80 ± 5.41） were obviously decreased in the XSECC large dose group, the medium dose group and the low dose group, compared with the model group （P〈0.05 or P〈0.01）; The content of MDA （1.44 ± 0.40 nmol/mg, 1.96 ± 1.13 nmol/mg, 2.12 ± 1.19 nmol/mg vs. 3.19 ± 0.98 umol/mg ）was decreased in the XSECC large dose group, the medium dose group and the low dose group when compared with the model group （P〈0.05 or P〈0.01 ）; The content of SOD （555.61 ± 92.45 U/mg, 607.90 ± 228.45 U/mg, 515.98 ± 184.01 U/mg vs. 348.12 ± 108.84 U/mg） was increased in the XSECC large dose group, the medium dose group and the low dose group when compared with the model group （P〈0.05 or P〈0.01）. Conclusion XSECC could protect injured neurons, which is related to the improvement of free radical metabolism. [ Key words ] Xiaoshuan enteric-coated capsule; Cerebral hypo-perfusion; NeuN; Caspase-3; Superoxide Dismutase; Malondialdehyde; Glutathione peroxidase