大黄对脓毒症相关大鼠脑功能障碍的作用机制研究  

Effects of Rhubarb on brain dysfunction in septic rats

作　　者：郭阿茹 马莉[1] 李杜鹏 张蓓[1] 安宏[1] Guo A - ru Ma Li Li Du - peng Zhang Bei An Hong.(Department of Emergency Intensive Care Unit, the Second Hospital of Lanzhou University, Lanzhou 730030, Chin)

机构地区：[1]兰州大学第二医院急诊危重症科,甘肃兰州730030

出　　处：《中国急救医学》2017年第10期878-883,I0001,共7页Chinese Journal of Critical Care Medicine

基　　金：北京协和医学基金会睿E（睿意）急诊医学研究专项基金（R2015003）

摘　　要：目的研究大黄对脓毒症相关大鼠脑功能障碍的作用及其可能作用机制。方法将84只Wistar大鼠随机分为盲肠结扎对照（Sham）组（分A、B小组）、盲肠结扎穿孔术（CLP）组（分A、B小组）和大黄灌胃＋CLP（R＋CLP）组（分A、B小组）。R＋CLP组给予大黄二甲基亚砜溶液经胃管灌胃，Sham组和CLP组仅给予二甲基亚砜溶液灌胃，通过CLP建立脓毒症大鼠模型。A组大鼠用于观察生存时间。B组大鼠分别于术后6、24、48h被处死，ELISA法测血清神经元特异性烯醇化酶（NSE）、S100α，右脑部分脑组织用于HE染色和免疫组化法测AQP-4表达情况，部分用ELISA法检测脑组织NF-κB、TNF-α、IL-6表达水平，左脑用于干湿质量法测含水量评价脑水肿情况。结果①CLP组和R＋CLP组脑组织含水量较Sham组明显增加；R＋CLP组术后6h脑组织含水量较CLP组术后6h显著降低。②CLP组和R＋CLP组脑组织炎性因子（NF-κB、IL-6和TNF-α）水平较Sham组明显升高；R＋CLP组术后24h脑组织炎性因子水平较CLP组术后24h明显降低。⑧CLP组和R＋CLP组血清NSE、S100β含量较Sham组明显升高；R＋CLP组术后24h血清NSE、S100β含量较CLP组术后24h明显降低。④光镜显示预使用大黄灌胃可减轻脓毒症后脑组织水肿程度，其中R＋CLP组术后6h脑组织水肿程度较CLP组术后6h明显减轻。⑤脑组织免疫组化：预使用大黄灌胃可降低脑组织胶质细胞表达AQP-4水平，其中R＋CLP组术后6h脑组织水肿程度较CLP组术后6h明显降低。⑥R＋CLP组不同时间点生存率较CLP组明显提高。结论预使用大黄对大鼠脓毒症相关脑功能障碍有明显的保护作用。Objective To investigate the effect of Rhubarb on brain dysfunction in septic rats. Methods A total of 84 Wistar male rats were randomly divided into three groups （ n = 28 each） , sham operation group（Sham）, cecal ligation and puncture group（ CLP）, Rhubarb ＋ CLP group （ R ＋ CLP）. Every group was then divided into two subgroups（A and B）. Female rats were garaged daily（ 1 mL/100 g body weight）with Rhubarb for three days. The same dose of saline was used in the control groups. Septic rat model was established by CLP. Survival rate was monitored in A groups, 10 days totally. In B groups, animals were euthanized at 12, 24 and 48 hours after CLP. Wet - dry weighting method was used to detect the brain water content （BWC）. The ELISA method was employed to determine the concentrations of plasma S100β, neuron-specific enolase （NSE）and the protein expression levels of brain tissue NF - κB, IL - 6 and TNF - α. Then Hematoxylin and Eosin （ HE ） staining was used to detect brain pathologic change. Immunohistochemical SP method was applied to count the number of AQP-4 positive glial ceils in brain tissues. Results ①The BWC values of the CLP and R ＋ CLP group at all time points were significantly higher than those of the sham group at the same periods （ P 〈0.05）, and which was lower in R ＋ CLP group than that in CLP group at 6 h after CLP （ P 〈 0.05 ）. ②CLP and R ＋ CLP groups brain tissue levels of NF - κB, IL - 6, and TNF -α were significantly increased compared with Sham group at each moment after CLP（ P 〈 0.05 ）, and R ＋ CLP group brain tissue levels of NF - κB, IL - 6, and TNF -α were also significantly lower than the CLP group at 24 h after CLP（P 〈0.05）. ③Compared with Sham group, the concentrations of plasma SlOOp, NSE were notably increased after CLP at each moment （ P 〈 0.05 ）, and which were significantly reversed by treatment with Rhubarb at 24 h after CLP （ P 〈 0. 05 ）. ④ Brain tissue HE staining showed the pathological

关 键 词：大黄 脓毒症 水通道蛋白-4 S100Β 神经元特异性烯醇化酶(NSE) 核转录因子-ΚB 白细胞介素-6 肿瘤坏死因子-α 

分 类 号：R-332[医药卫生]