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目的:研究血管紧张素I受体(AT1)抑制剂厄贝沙坦对侧位液压脑损伤模型大鼠神经细胞凋亡的影响。方法:利用改良的侧位液压损伤装置建立大鼠颅脑损伤(TBI)模型,术前及术后给予厄贝沙坦治疗,用激光多普勒测定局部脑区血流(r CBF)的变化,术前及术后1、3、5和7d利用神经功能评分评估大鼠神经功能损伤,利用TUNEL染色检测大鼠脑细胞凋亡情况,利用Western Blot检测大鼠脑组织损伤周围区域活性caspase 3的表达。结果:与正常值相比,TBI手术后损伤局部脑区r CBF下降至30%(P<0.05),神经功能评分显著降低(P<0.05),损伤区周围脑组织TUNEL阳性细胞明显增多,活性caspase 3的表达显著增加(P<0.05)。厄贝沙坦治疗组大鼠r CBF显著高于单纯TBI组,梗死区面积显著缩小,神经功能得到明显改善,损伤区周围脑组织TUNEL阳性细胞和活性caspase 3表达下降(P均<0.05)。结论:厄贝沙坦预处理能够通过抑制凋亡发挥神经保护作用。
AIM: To investigate the effect of irbesartan, an angiotensin I receptor (AT1) inhibitor, on neuronal apoptosis in a lateral hydraulic brain injury model. Methods: A rat model of traumatic brain injury (TBI) was established by using a modified lateral hydraulic injury device. Irbesartan was given before and after operation, and the changes of r CBF in the brain were measured by laser Doppler. Neurological deficits were evaluated by neurological function before, 1, 3, 5 and 7 days after operation. TUNEL staining was used to detect the apoptosis of rat brain. Western Blot was used to detect the expression of active caspase 3 expression. Results: Compared with the normal value, the rBFF decreased to 30% (P <0.05), the neurological function score decreased significantly (P <0.05), and the TUNEL positive cells in the brain tissue around TBI increased significantly after TBI The expression of caspase 3 increased significantly (P <0.05). The r CBF in irbesartan treatment group was significantly higher than that in the simple TBI group. The area of infarction area was significantly reduced and the neurological function was significantly improved. The expression of TUNEL positive cells and active caspase 3 in brain tissue around the lesion area were decreased (all P <0.05). Conclusion: Irbesartan preconditioning can exert neuroprotective effects by inhibiting apoptosis.