破血化瘀、填精补髓中药汤剂对实验性脑出血大鼠Keap1-Nrf2/HO-1途径相关蛋白表达的影响  

Influence of Chinese medicine decoction with effects of activating blood and removing stasis and supplementing essence and marrow on related proteins expression of Keap1-Nrf2/HO-1 pathway in experimental cerebral hemorrhage rats

作　　者：赵树明[1] 李佳欣 杜艳伟 李倩雯 李萍[3] 

机构地区：[1]长春中医药大学学生处,吉林长春130117 [2]长春中医药大学针灸推拿学院,吉林长春130117 [3]长春中医药大学基础医学院,吉林长春130117 [4]长春中医药大学附属医院,吉林长春130021

出　　处：《上海中医药杂志》2017年第11期79-83,共5页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(81603557);长春中医药大学"百青计划"资助项目

摘　　要：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 influence of Chinese medicine decoction,that with the effects of activating blood and removing stasis and supplementing essence and marrow,on the protein expressions of Kelch-like epichlorohydrin-associated protein 1（ Keap1）,nuclear factor erythroid 2-related factor 2（ Nrf2） and heme oxygenase-1（ HO-1） in experimental model rats with cerebral hemorrhage. Methods 64 male Wistar rats were randomly divided into the sham operation group,model group,positive control group（ Naoxuekang Capsule） and Chinese medicine decoction group,16 rats in each group. The rat model of cerebral hemorrhage was established by injection of autologous blood into the caudate nucleus. Each group was treated with the corresponding drugs once a day. 3 days later,the rats were anesthetized,the brain tissue was collected and the water content was detected. The morphological changes of nerve cells in caudate nucleus of rat brain were observed by HE staining. The expressions of Keap1,Nrf2 and HO-1 in brain tissue of rats in each group were detected by immunohistochemistry.Results Compared with the sham operation group,the brain water content of rats in the model group was obviously increased（ P 0. 05）; compared with the model group,the brain water content was obviously decreased in the positive control group and Chinese medicine decoction group,and the decrease in the decoction group was more significant（ P 0. 05）. Compared with the sham operation group,a large amount of red blood cell infiltration in the hematoma area of brain caudate nucleus were observed in rats of the model group,the number of nerve cells decreased and the glial cells increased with obvious interstitial edema,and the nerve cells presented disordered and sparse arrangement with light staining. Compared with the model group,there were a small amount of red blood cell infiltration in the brain caudate nucleus of rats in the positive control group and Chinese medicine decoction group,the nerve cells slightly swelled and loosely arra

关 键 词：脑出血 破血化瘀 填精补髓法 Keap1-Nrf2/HO-1 

分 类 号：R285.5[医药卫生—中药学]