芪红通络颗粒对大鼠脑缺血再灌注损伤保护作用及其机制研究

目的 观察芪红通络颗粒对大鼠脑缺血再灌注损伤的保护作用，并初步探讨其作用机制。方法 将SD大鼠随机分为假手术组，模型组，尼莫地平组，芪红通络颗粒高、中、低剂量（10.8、5.4、2.7 g/kg）组，采用线栓法建立大鼠局灶性脑缺血再灌注损伤模型。各组大鼠术前连续3 d、术后连续2 d灌胃给药，每日1次。术后72 h采用Longa法进行神经功能缺损评分，TTC染色法测定脑梗死体积，HE染色观察脑组织病理学改变，比色法测定脑组织丙二醛（malondialdehyde, MDA）含量和超氧化物歧化酶（superoxide dismutase, SOD）、谷胱甘肽过氧化物酶（glutathion peroxidase,GSH- Px）活力，Western blot法测定脑组织核因子E2相关因子2（nuclear factor erythroid- 2 related factor 2, Nrf2）和血红素氧合酶- 1（heme oxygenase 1, HO- 1）蛋白表达水平。结果 与模型组比较，芪红通络颗粒高、中、低剂量组脑梗死体积显著缩小（P＜0.05）；高、中剂量组神经行为学障碍症状明显减轻（P＜0.05），脑组织病理改变明显减轻；高、中、低剂量组脑组织中MDA含量明显降低，SOD和GSH- Px活力明显增加（P＜0.05）；高、中剂量组脑组织中Nrf2和HO- 1蛋白表达水平明显升高（P＜0.05）。结论 芪红通络颗粒对大鼠脑缺血再灌注损伤具有较好的保护作用，其机制可能与其激活Nrf2/HO- 1信号通路，抑制氧化应激反应，从而产生抗氧化作用有关。

Protective Effect of Qihong Tongluo Granule Against Cerebral Ischemia/Reperfusion Injury in Rats and Its Mechanism

Objective To investigate the protective effect of Qihong Tongluo Granule against cerebral ischemia/reperfusion injury in rats and its preliminary mechanism of action. Methods Sprague- Dawley rats were randomly divided into sham- operation group, model group, nimodipine group, and high- , middle- , and low- dose (10.8,5.4, and 2.7 g/kg) Qihong Tongluo Granule groups. The suture method was used to establish a rat model of focal cerebral ischemia/reperfusion injury. The rats were administered once a day by gavage for 3 consecutive days before surgery and 2 consecutive days after surgery. At 72 hours after surgery, the Longa method was used to determine neurological deficit score; TTC staining was used to measure cerebral infarct volume; HE staining was used to observe the pathological changes of brain tissue; colorimetry was used to measure the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH- Px) in brain tissue; Western blot was used to measure the protein expression levels of nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase- 1 (HO- 1) in brain tissue. Results Compared with the model group, the high- , middle- , and low- dose Qihong Tongluo Granule groups had a significant reduction in cerebral infarct volume (P<0.05); the high- and middle- dose Qihong Tongluo Granule groups had significantly alleviated symptoms of neurobehavioral disturbance (P<0.05) and pathological changes of brain tissue; the high- , middle- , and low- dose Qihong Tongluo Granule groups had a significant reduction in the content of MDA and significant increases in the activities of SOD and GSH- Px in brain tissue (P<0.05); the high- and middle- dose Qihong Tongluo Granule groups had significant increases in the protein expression levels of Nrf2 and HO- 1 in brain tissue (P<0.05). Conclusion Qihong Tongluo Granule exerts a good protective effect against cerebral ischemia/reperfusion injury in rats, possibly by activating the Nrf2/HO- 1 signaling pathway, inhibiting oxidative stress response, and thus producing an antioxidant effect.