基于SUR1基因探讨川芎嗪治疗创伤性脑损伤的机制  

Mechanism of tetramethylpyrazine treating traumatic brain injury based on SUR1 gene

作　　者：余万[1] 葛玉元[1] 张勇[1] YU Wan;GE Yuyuan;ZHANG Yong(Department of Neurosurgery,Affiliated Hospital of Traditional Chinese and Western Medicine,Nanjing University of Chinese Medicine,Nanjing 210028,China)

机构地区：[1]南京中医药大学附属中西医结合医院神经外科,南京210028

出　　处：《山西医科大学学报》2020年第11期1226-1231,共6页Journal of Shanxi Medical University

基　　金：江苏省中医药局科技项目(YB201820)。

摘　　要：目的探讨川芎嗪治疗创伤性脑损伤(traumatic brain injury,TBI)的作用机制,为临床开发安全有效的TBI治疗药物奠定基础。方法SPF级ICR雄性小鼠50只随机分为假手术组、模型组和川芎嗪低(15 mg/kg)、中(30 mg/kg)、高(60 mg/kg)剂量组,每组10只。采用Feeney自由落体撞击法制作TBI小鼠模型,假手术组开颅窗后不给予颅脑撞击。损伤2 h给药组小鼠腹腔注射相应剂量的川芎嗪,每天1次,而假手术组和模型组小鼠给予等量生理盐水,连续给药7 d。于建模损伤后1,3,7 d进行神经功能缺损评分(mNSS),并检测脑组织含水量和炎症因子水平,同时采用Western blot方法检测脑磺酰脲受体1(SUR1)、M4型瞬时受体电位通道(TRPM4)、水通道蛋白4(AQP4)、丝裂原激活的蛋白激酶p38(p38 MAPK)等相关因子的蛋白及磷酸化蛋白水平。结果与模型组相比,川芎嗪低、中、高剂量组小鼠第7天mNSS评分和脑组织含水量降低(P<0.05-0.001),中、高剂量组脑组织炎症因子IL-1β、IL-6和TNF-α的含量明显降低(P<0.05或P<0.01)。与模型组相比,川芎嗪组中、高剂量组小鼠脑组织SUR1、TRPM4、AQP4和p-p38蛋白表达水平下降(P<0.05或P<0.01)。结论川芎嗪可能通过调控SUR1,从而调控其下游靶蛋白TRPM4、AQP4和p38,进而改善TBI。Objective To explore the mechanism of tetramethylpyrazine in the treatment of traumatic brain injury(TBI),and lay a foundation for the clinical development of safe and effective TBI drugs.Methods Fifty male SPF-grade ICR mice were randomly divided into sham operation group,model group,and low(15 mg/kg tetramethylpyrazine),medium(30 mg/kg tetramethylpyrazine),and high(60 mg/kg tetramethylpyrazine)dose groups,with 10 mice in each group.The TBI mouse model was made using the Feeney free-fall impact method,and no brain impact was given after craniotomy in sham operation group.The mice in tetramethylpyrazine groups were injected intraperitoneally with the corresponding doses of tetramethylpyrazine 2 h after the injury once a day,while the mice in sham operation group and model group were given the same amount of normal saline for 7 d.Neurological deficit scores(mNSS)were performed at 1,3,7 d after injury,and the brain tissue water content and inflammatory factor levels were measured.At the same time,Western blot was used to detect the levels of brain sulfonylurea receptor 1(SUR1)and M4 transient receptor potential protein and phosphorylated proteins of channels(TRPM4),aquaporin 4(AQP4),mitogen-activated protein kinase p38(p38 MAPK)and other related factors.Results Compared with model group,the mNSS score at 7 d and brain tissue water content were significantly decreased in low,medium and high dose groups(P<0.05-0.001),and the contents of brain tissue inflammatory factors IL-1β,IL-6 and TNF-αwere significantly decreased in medium and high dose groups(P<0.05 or 0.01).At the same time,compared with model group,the levels of SUR1,TRPM4,AQP4 and p-p38 protein expression in brain tissues were significantly decreased in medium and high dose groups(P<0.05 or 0.01).Conclusion Tetramethylpyrazine can improve TBI by regulating SUR1 downstream target proteins TRPM4,AQP4 and p38.

关 键 词：创伤性脑损伤 SUR1基因 川芎嗪 络病 

分 类 号：R642[医药卫生—外科学]