目的 探讨益气活血通络方对蛛网膜下腔出血大鼠TGF-β/ERK信号通路的影响及神经保护作用。方法 SD大鼠随机分为假手术组，模型组，益气活血通络方5、10、15 g/kg组和尼莫地平组，除假手术组外，其余各组建立蛛网膜下腔出血模型大鼠，分组处理后，各组大鼠进行神经功能缺损评分；以伊文思蓝染料外渗实验检测大鼠血脑屏障通透性；以TUNEL染色检测大鼠脑皮质神经细胞凋亡情况；以酶联免疫吸附法（ELISA）检测大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平；以蛋白免疫印迹法检测大鼠脑皮质组织TGF-β/ERK通路相关蛋白TGF-β1、p-ERK/ERK表达情况。结果 与假手术组相比，模型组大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例、血清IL-6、TNF-α水平、TGF-β1表达、p-ERK/ERK明显升高（P<0.05）。与模型组相比，益气活血通络方5、10、15 g/kg组和尼莫地平组大鼠神经功能缺损评分、伊文思蓝渗出量、TUNEL阳性细胞比例、血清IL-6、TNF-α水平、TGF-β1表达和p-ERK/ERK水平明显降低（P<0.05），且益气活血通络方各组呈剂量相关性，益气活血通络方15 g/kg组与尼莫地平组相比，各指标比较差异无统计学意义。结论 益气活血通络方可下调TGF-β/ERK信号，保护蛛网膜下腔出血大鼠神经功能。

Objective To investigate the neuroprotective effect of Yiqi Huoxue Tongluo Prescription on TGF-β/ERK signal pathway in rats with subarachnoid hemorrhage. Methods SD rats were randomly divided into sham operation group, model group, Yiqi Huoxue Tongluo Prescription Yiqi Huoxue Tongluo Prescription 5, 10, and 15 g/kg groups, and nimodipine group. In addition to the sham operation group, the other rats were established to establish subarachnoid hemorrhage model, after group treatment, the rats in each group were assessed for neurological deficit. Evans blue extravasation test was used to detect the permeability of BBB. TUNEL staining was used to detect the apoptosis of neurons. The levels of serum TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA), and the expressions of TGF-β1 and p-ERK/ERK in the cortex of rats were detected by Western blotting. Results Compared with the sham group, the neurological deficit score, seepage amount of Evans blue, proportion of TUNEL positive cell, levels of serum IL-6 and TNF-α, expression of TGF-β1, and p-ERK/ERK of rats in the model group were significantly increased (P<0.05). Compared with the model group, the neurological deficit score, seepage amount of Evans blue, proportion of TUNEL positive cell, levels of serum IL-6 and TNF-α, expression of TGF-β1 and p-ERK/ERK of rats in the Yiqi Huoxue Tongluo Prescription 5, 10, and 15 g/kg groups and nimodipine group were decreased (P<0.05), and Yiqi Huoxue Tongluo Prescription groups were dose-dependent, in addition, there was no significant difference in the indexes between Yiqi Huoxue Tongluo Prescription 15 g/kg group and nimodipine group. Conclusion Yiqi Huoxue Tongluo Prescription can down regulate TGF-β/ERK signal and protect the nerve function of rats with subarachnoid hemorrhage.

R966;R285.5

河南省科技研发专项项目（162102310120）