涤痰通瘀方干预急性脑出血大鼠肝组织IRAK-M表达变化的影响

王威1，许晓英1，马迪1，赵海滨1*，唐杰2，张秀静1，王帅1，翟瑶瑶1，张淑静3

(1.北京中医药大学第三附属医院，北京 100029；2.北京房山区中医医院，北京 102400；

3.北京中医药大学，北京 100029)

摘要：目的研究急性脑出血大鼠肝组织中IRAK-M表达的变化,并探讨涤痰通瘀方剂对急性脑出血大鼠肝损害的干预作用。方法通过建立SD大鼠急性脑出血模型，并随机分为中药组(酒大黄、胆南星、石菖蒲、蒲黄、三七、水蛭)、脑出血组、假手术组、正常组，每组分为24、48、72 h 3个时间亚组,检测每组肝脏组织IRAK-M蛋白表达水平及肝组织肿瘤坏死因子-α(TNF-α)水平,并观察肝组织HE染色结果。结果脑出血模型组在造模后各个时间点IRAK-M蛋白表达水平较假手术组及正常组均明显降低(P<0.05)；中药治疗组的IRAK-M蛋白表达水平较脑出血模型组明显升高(P<0.05)，与假手术组、正常组相比略有降低；中药治疗组及脑出血模型组肝脏IRAK-M蛋白表达水平与组织TNF-α水平呈负相关。结论IRAK-M蛋白表达水平升高可能是抑制脑出血后诱发的LPS胞内信号转导炎性级联反应的重要因素；涤痰通瘀方剂可加强IRAK-M激酶活性，从而抑制炎症因子的释放,减轻急性脑出血大鼠肝脏损伤的程度。

关键词：白细胞介素-1受体相关激酶-M;急性脑出血;肝损害;涤痰通瘀法;肿瘤坏死因子-α

DOI:10.13463/j.cnki.jlzyy.2015.11.023

中图分类号：R285.5文献标志码： A

基金项目:国家自然科学基金(81373590)。

作者简介:王威(1983-)，女，硕士研究生，主要从事中西医结合防治心脑血管疾病研究。

收稿日期:(责任编辑：张瑞彬2014-12-16)

*通信作者:赵海滨,电话-(010)52075211,电子信箱-haibin999@126.com

IRAK-M in liver during acute cerebral hemorrhage and effects of Ditantongyu measure

WANG Wei1,XU Xiaoying1,MA Di1,ZHAO Haibin1*,TANG Jie2,ZHANG Xiujing1,

WANG Shuai1,ZHAI Yaoyao1,ZHANG Shujing3

(1.The 3rd Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China;

2.Fangshan District Hospital of Traditional Chinese Medicine,Beijing 102400,China;

3.Beijing University of Chinese Medicine,Beijing 100029,China)

Abstract:ObjectiveTo investigate the change of expression of IRAK-M in liver during Acute Cerebral Hemorrhage,and discuss the protection mechanism of Ditantongyu Measure.MethodsThe model of acute cerebral hemorrhage was established.The animals were randomly divided into three groups: TCM treatment group (the rhubarb,bravery south star,stone calamus,cattail pollen,notoginseng,leech),cerebral hemorrhage group,sham surgery group,blank control group.And each group was further divided into 3 time-point sub-groups of 24,48 and 72 h.The expression level of hepatic IRAK-M protein was measured,the hepatic content of tumor necrosis factor-alpha (TNF-α) were detected,and HE staining results of liver tissue are observed.ResultsCompared with Group S and Group B,the expression levels of IRAK-M protein at each time-point post-modeling in both Groups T had markedly reduced (P<0.05).Groups T elevated markedly compared with Group C (P<0.05),but it decreased in Group S and Group B.The expression level of hepatic IRAK-M protein in Group T and Group C was negatively correlated with the changes of hepatic content of TNF-α.ConclusionIncrease of IRAK-M protein expression may be an important factor in the inhibition of after cerebral hemorrhage induced intracellular signal transduction of the inflammatory cascade reaction;Ditantongyu Measure can enhance the activity of IRAK-M,and it can restrain release of inflammatory factor,thus alleviating liver injury of rats with acute cerebral hemorrhage.

Keywords:Inter-leukin-1 Receptor Associated Kinase-M (IRAK-M);acute cerebral hemorrhage;liver injury;Ditantongyu measure;tumor necrosis factor-alpha (TNF-α)

急性脑出血是一种常见的脑血管疾病，极易致残，甚至导致全身炎症反应综合征(SIRS)，或多器官功能障碍综合征(MODS)，更严重者可出现死亡。急性脑出血后，下丘脑功能紊乱，使内毒素生成增加，同时肠黏膜屏障受损，继而发生细菌易位，形成肠源性内毒素血症，最终导致肝损害[1]。内毒素又名脂多糖(LPS),可激活单核-巨噬细胞系统(MPS)，引起肝组织肿瘤坏死因子-α(TNF-α)等炎症介质大量释放，从而导致肝损伤[2]。……