巴戟天醇提物通过MAPK/ERK信号通路对脑缺血再灌注模型大鼠的保护作用  

Protective effect of radix Morindae officinalis-ethanolic extract on a rat model of cerebral ischemia-reperfusion by the regulation of MAPK/ERK signaling

作　　者：龚鸣 GONG Ming(Department of Traditional Chinese Medicine,Jinhua People's Hospital,Jinhua 321000,China)

机构地区：[1]浙江省金华市人民医院中医科,金华321000

出　　处：《浙江中西医结合杂志》2021年第9期798-803,816,共7页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

摘　　要：目的探究巴戟天醇提物(RMOEE)对脑缺血再灌注模型大鼠的保护机制。方法将40只雄性SD大鼠按照随机数字表法分为假手术组、模型组及RMOEE低、中、高剂量组,每组8只。采用线栓法制备脑缺血再灌注模型大鼠,RMOEE低、中、高剂量组分别按照3、6、12g/kg的剂量灌胃给药,假手术组和模型组大鼠给予等体积羧甲基纤维素钠溶液。给药21天后,采用Zea Longa评分标准对各组大鼠进行神经功能评分,并采用干湿重法检测脑含水量,酶联免疫法检测大鼠缺血侧脑组织炎症因子表达,采用2,3,5-氯化三苯基四氮唑(TTC)染色法测定大鼠脑梗死体积百分比,苏木精-伊红(HE)染色法检测大鼠脑神经元病理学改变,原位末端转移酶标记(TUNEL)染色法检测大鼠脑组织凋亡,Western blot法检测相关蛋白表达情况。结果与模型组比较,RMOEE各剂量组能够降低Zea Longa评分[(2.2±0.3)分、(1.9±0.3)分、(1.5±0.3)分比(3.6±0.4)分,P<0.05或P<0.01];并且与模型组比较,RMOEE中、高剂量组大鼠脑含水量明显减少[(80.2±4.3)%、(73.4±2.8)%比(88.5±1.9)%,P均<0.05],脑梗死体积百分比明显降低[(35.9±0.3)%、(18.5±0.3)%比(45.6±5.4)%,P<0.05或P<0.01],脑组织肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、细胞内黏附分子-1(ICAM-1)及血管细胞黏附分子-1(VCAM-1)的表达水平显著降低[TNF-α:(668.78±25.12)nmol/L、(488.02±40.28)nmol/L比(783.76±44.42)nmol/L;IL-1β:(540.92±22.98)nmol/L、(413.22±20.71)nmol/L比(680.61±39.74)nmol/L;ICAM-1:(255.40±14.25)pg/mL、(201.42±21.42)pg/mL比(292.26±16.32)pg/mL;VCAM-1:(42.20±3.83)pg/mL、(35.71±2.18)pg/mL比(54.90±5.56)pg/mL,P均<0.05];RMOEE各剂量组脑神经元病理学改变得到有效改善,中、高剂量组大鼠脑组织细胞凋亡率明显降低[(40.80±1.90)%、(35.36±1.80)%、(29.60±1.53)%比(48.90±2.80)%,P均<0.05],MAPK/ERK信号通路相关蛋白表达降低[p-MEK1/2:(1.99±0.13)、(0.66±0.09)比(2.62±0.21);p-ERK1/2:(0.99±0.06)�Objective To investigate the protective effect and molecular mechanism of radix Morindae officinalis-ethanolic extract(RMOEE)on a rat model of cerebral ischemia reperfusion.Methods A total of 40 male Sprague-Dawley rats were randomly divided into sham,model,and RMOEE(low,medium,and high doses)groups(n=8 in each group).The rat model of cerebral ischemia reperfusion was established by using the suture embolization method.The RMOEE(low,medium,and high doses)was intragastrically administrated into rats at 3,6,and 12g/kg of RMOEE,respectively,while the shame and model rats were treated with an equal volume of sodium carboxymethyl cellulose daily for 21 days.Next,the Zea Longa method was used to score the nerve function of each rat and the wet weight method was used to assess the brain water content.ELISA was used to measure levels of inflammatory factors in rat ischemic lateral brain tissues,the TTC staining was performed to assess the percentage of cerebral infarction volume,hematoxylin and eosin(HE)staining was used to assess the pathological changes in rat neurons,the TUNEL assay was used to assess the level of brain tissue apoptosis and Western blot was used to determine the expression of various related proteins in the brain tissues.Results Compared with the model group,each RMOEE dose group reduced the Zea Longa score(2.2±0.3,1.9±0.3,and 1.5±0.3 vs.3.6±0.4;P<0.05 or P<0.01),and the water content in rat brain after the medium and high doses of RMOEE treatment was significantly decreased(80.2±4.3 and 73.4±2.8 vs.88.5±1.9%;all P<0.05).The percentage of cerebral infarction volume was also significantly decreased after the medium and high doses of RMOEE treatment(35.9±0.3 and 18.5±0.3 vs.45.6±5.4%;P<0.05 or P<0.01).Furthermore,expression of tumor necrosis factor-α(TNF-α),interleukin 1beta(IL-1β),intracellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)was also significantly inhibited after the medium and high doses of RMOEE treatment(TNF-α,668.78±25.12 and 488.02±40.28 vs.

关 键 词：大鼠 巴戟天醇提物 MAPK/ERK信号通路 脑缺血再灌注 炎症 凋亡 

分 类 号：R285.5[医药卫生—中药学]