SHH信号通路对大脑中动脉梗死模型大鼠脑缺血后的保护作用

目的 探讨SHH信号通路对大脑中动脉梗死(middle cerebral artery occlusion,MCAO)模型大鼠脑缺血后的保护作用。 方法 选择30只SD雄性大鼠，按随机数字表法随机分为3组，分别为假手术组、模型组和SHH组，各10只。以改良Longa线栓法制备MCAO模型，其中假手术组颈内外动脉和颈总动脉分离，不结扎也不插线栓。SHH组于大鼠左侧侧脑室注射SHH蛋白注射液2 μL (1 μg/μL)，假手术组和模型组注射等量PBS溶液。观察各组术后3 d和7 d神经功能评分、脑梗死体积、脑血流值变化，周期素依赖性激酶2抗体(cyclin-dependent-kinase 2,CDK2)和细胞周期素D1(CyclinD1)表达。 结果 SHH组神经功能评分术后3 d[(1.23±0.16)分]和术后7 d[(0.87±0.13)分]低于模型组[(2.10±0.25)分、(2.38±0.19)分,t=9.269、20.741,均P<0.05)。SHH组术后3 d［(32.14±7.25) mm3]和术后7 d[(21.98±4.56) mm3]梗死体积低于模型组[(60.27±5.64) mm3、(64.82±7.19) mm3，t=9.684、15.912,均P<0.05)。SHH组术后3 d［(348.92±29.38) PU]和术后7 d[(413.24±56.29) PU]脑血流值高于模型组［(163.28±26.13) PU、(130.29±23.42) PU,t=14.930、14.676,均P<0.05)。SHH组CDK2(27.18±3.10)和CyclinD1(24.52±4.31)低于模型组(59.83±5.62、67.38±7.39，t=16.087、15.843，均P<0.05)。 结论 SHH信号通路可减轻MCAO模型大鼠脑缺血后神经功能损伤，减少脑梗死体积，且可通过调控CDK2和CyclinD1表达使神经细胞增殖，诱导神经再生，达到神经保护作用。 

Protective effect of SHH signaling pathway on middle cerebral artery occlusion model rats after cerebral ischemia

Objective To investigate the protective effect of SHH signaling pathway on middle cerebral artery occlusion (MCAO) model rats after cerebral ischemia. Methods Total 30 SD rats were randomly divided into three groups:sham operation group, model group and SHH group, 10 rats each groups. The MCAO model was made by the modified longa suture method. In the SHH group, 2 μL (1 μg/μL) SHH protein was injected into the left lateral ventricle, and the same amount of PBS solution was injected into the sham operation group and the model group. Results The neurological function scores of the SHH group were lower than those of the model group at 3 days (1.23±0.16 vs. 2.10±0.25) and 7 days (0.87±0.13 vs. 2.38±0.19) after operation (t=9.269, 20.741, all P<0.05). The infarct volume of the SHH group were lower than those of the model group at 3 days (32.14±7.25 vs. 60.27±5.64) and 7 days (21.98±4.56 vs. 64.82±7.19) after operation (t=9.684, 15.912, all P<0.05. The value of cerebral blood flow in the SHH group were higher than that in the model group at 3 days[(348.92±29.38) PU vs. (163.28±26.13) PU] and 7 days[(413.24±56.29) PU vs. (130.29±23.42) PU] after operation (t=14.930, 14.676, all P<0.05). The CDK2 (27.18±3.10) and CyclinD1 (24.52±4.31) in the SHH group were lower than those in the model operation group (59.83±5.62 and 67.38±7.39), t=16.087, 15.843, all P<0.05. Conclusion SHH signaling pathway can reduce the neurological damage of cerebral infarction in MCAO model rats after cerebral ischemia, it can regulate the expression of CDK2 and CyclinD1 to achieve the neuroprotective effect.