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目的观察以破血化瘀、填精补髓法组方的中药汤剂对实验性脑出血模型大鼠Kelch样环氧氯丙烷相关蛋白-1(Keap1)、核转录因子E_2相关因子2(Nrf2)和血红素加氧酶(heme oxygenase,HO)-1蛋白表达的影响。方法将64只Wistar雄性大鼠随机分为4组:假手术组、模型组、脑血康胶囊阳性对照药组(简称阳性药组),以及破血化瘀、填精补髓中药汤剂组(简称汤剂组),每组16只。采用尾状核注射自体血方法制作大鼠脑出血模型,分别给药(1次/d),3天后,麻醉下取大鼠脑组织,检测脑含水量,采用HE染色观察鼠脑尾状核神经细胞的形态变化,采用免疫组织化学方法检测各组大鼠脑组织Keap1、Nrf2、HO-1的表达变化。结果模型组大鼠脑含水量与假手术组比较明显增加(P<0.05);阳性药组和汤剂组脑含水量与模型组比较均明显下降,尤以汤剂组下降明显(P<0.05)。与假手术组比较,模型组大鼠脑尾状核血肿区可见大量红细胞浸润,神经细胞数目减少,胶质细胞增多,间质水肿明显,神经细胞排列紊乱、稀疏、淡染;与模型组比较,汤剂组和阳性药组大鼠脑尾状核均可见少量红细胞浸润,神经细胞略微肿胀,间质水肿较轻,神经细胞排列略疏松。与假手术组比较,模型组大鼠脑组织Keap1、Nrf2和HO-1的表达增加(P<0.01);与模型组比较,阳性药组和汤剂组大鼠脑组织肿Keap1、Nrf2和HO-1表达减少(P<0.01),其中汤剂组较阳性药组改善显著(P<0.05)。结论破血化瘀、填精补髓中药汤剂可通过Keap1-Nrf2/HO-1途径改善脑组织氧化应激状态,进而保护脑出血后继发损伤的脑组织。
Objective To observe the effect of Kelu-like epichlorohydrin-related protein-1 (Keap1), nuclear factor-2 (Nrf2) ) And heme oxygenase (HO) -1 protein expression. Methods Sixty-four Wistar male rats were randomly divided into 4 groups: sham-operation group, model group, Naoxuekang capsule positive control group (referred to as positive drug group), and blood-clearing and blood- (Referred to as decoction group), each group of 16. The model of intracerebral hemorrhage was made by caudate nucleus injection of autologous blood. The rats were respectively administered once a day for 3 days. The brain tissue was taken under anesthesia, the brain water content was measured, and the brain caudate nucleus was observed by HE staining. The morphological changes of nerve cells were detected by immunohistochemistry. The changes of the expression of Keap1, Nrf2 and HO-1 in brain of each group were detected. Results The brain water content in model group was significantly increased compared with that in sham operation group (P <0.05). The brain water content in positive drug group and decoction group decreased significantly compared with model group, especially in decoction group (P <0.05) ). Compared with the sham-operated group, a large number of erythrocyte infiltration was found in the hematoma region of the cerebral caudate nucleus in the model group, the number of the nerve cells decreased, glial cells increased, the interstitial edema was obvious, the nerve cells arranged disorder, sparse and lightly stained; Compared with the model group In the decoction group and the positive drug group, a small amount of erythrocyte infiltration was seen in the caudate nucleus of the rat brain, with slight swelling of the nerve cells, less interstitial edema, and a slight loose arrangement of nerve cells. Compared with the sham-operation group, the expression of Keap1, Nrf2 and HO-1 in the model group increased (P <0.01). Compared with the model group, the expression of Keap1, Nrf2 and HO in the positive group and the decoction group -1 (P <0.01), and the decoction group had a significant improvement (P <0.05) compared with the positive group. Conclusion The method of Keap1-Nrf2 / HO-1 can improve the oxidative stress state of brain tissue after decoction of blood-stasis and eliminate blood stasis and fill the essence of marrow-tonifying decoction, and then protect the brain tissue that is damaged after cerebral hemorrhage.