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目的观察卵巢摘除对线栓阻塞大脑中动脉法(MCAO)大鼠环磷酸腺苷反应元件结合蛋白(CREB)表达的影响以及补肾益精方剂左归丸的干预作用,探索中医学“肾通于脑”理论的现代生物学基础。方法 Wistar雌性大鼠64只,随机分为4组,即假手术组、缺血组、卵巢摘除+缺血组、卵巢摘除+缺血+中药组,每组16只。除假手术组外,其余各组均用MCAO建立脑缺血模型,并于缺血2 h后实施再灌注。卵巢摘除+缺血组在MCAO手术前10天进行双侧卵巢摘除;卵巢摘除+缺血+中药组在MCAO手术前10天进行双侧卵巢摘除,并于MCAO手术前3天给予左归丸汤剂(1.62 g/kg)灌胃,每日1次,连续给药10天。采用免疫组化及Western blotting法检测CREB水平。结果与假手术组比较,缺血组CREB表达增加(P<0.05);与缺血组比较,卵巢摘除+缺血组CREB表达明显下调(P<0.05);与卵巢摘除+缺血组比较,卵巢摘除+缺血+中药组CREB表达明显增加(P<0.05)。结论脑缺血后CREB表达增加可能是机体的一种保护性反应;性激素剥夺可加重脑缺血再灌注所致的脑损伤且下调CREB表达,左归丸对卵巢摘除大鼠脑缺血损伤有修复作用并可上调CREB表达;提示补肾中药左归丸有类性激素样作用,并可通过上调CREB表达促进缺血性脑损伤的恢复。
Objective To observe the effects of ovariectomy on the expression of cyclic adenosine monophosphate response element binding protein (CREB) in rats with occlusion of middle cerebral artery occlusion (MCAO) and the intervention of Zuogui Pill of Bushenyijing Recipe In the brain "theory of modern biology. Methods Sixty-four Wistar female rats were randomly divided into 4 groups: sham operation group, ischemia group, ovariectomy + ischemia group, ovariectomy + ischemia + TCM group, 16 in each group. In addition to the sham-operation group, MCAO was used to establish the model of cerebral ischemia, and reperfusion was performed 2 h after ischemia. Ovariectomized + ischemic group bilateral ovariectomy 10 days prior to MCAO surgery; ovariectomy plus ischemia + Chinese medicine group bilateral ovarian removal 10 days prior to MCAO surgery, and given 3 days before MCAO surgery Zuogui pill soup (1.62 g / kg) orally, once daily for 10 consecutive days. The level of CREB was detected by immunohistochemistry and Western blotting. Results Compared with the sham operation group, the expression of CREB increased in ischemic group (P <0.05). Compared with ischemia group, the expression of CREB in ovariectomized + ischemic group was significantly decreased (P <0.05) Ovarian ablation + ischemia + CREB expression was significantly increased (P <0.05). Conclusions Increased expression of CREB after cerebral ischemia may be a protective response to the body. Sex hormone deprivation may increase brain injury induced by cerebral ischemia-reperfusion and down-regulate CREB expression. Zuogui pill has protective effect on cerebral ischemia in ovariectomized rats Repair effect and up-regulate the expression of CREB. It suggests that the kidney-tonifying Chinese medicine Zuo Gui Wan has sex-hormone-like effects and can promote the recovery of ischemic brain injury by up-regulating the expression of CREB.