目的 基于髓样分化因子 88（MyD88）/细胞外信号调节激酶（ERK）通路及核因子 κB（NF-κB）核移位探讨 大黄素对局灶性脑缺血大鼠的作用及机制。方法 将 SD 大鼠按随机数字表法分为假手术组、模型组、大黄素 组，每组 6 只，采用大脑中动脉栓塞法建立大脑中动脉短暂性闭塞模型（tMCAO）。大黄素组大鼠于造模前 72、 48、24 h，分别给予 40 mg·kg-1大黄素灌胃给药，共 3 次。造模结束后 24 h，对大鼠进行神经功能评分；采用 TTC 染色法检测脑组织梗死灶面积；HE 染色法观察脑组织形态变化；RT-qPCR 法检测脑组织中 MyD88、肿瘤 坏死因子 α（TNF-α）mRNA 表达水平；Western Blot 法检测脑组织中 MyD88、ERK、p-ERK、TNF-α 蛋白表达 水平；免疫荧光法检测脑组织中 NF-κB 蛋白表达。结果 与假手术组比较，模型组大鼠神经功能评分显著升 高（P＜0.01），脑梗死面积显著增加（P＜0.01）；缺血半暗带皮质区中出现细胞坏死，细胞形态异常，胞核破碎 萎缩，细胞数量明显降低；脑组织中 MyD88、TNF-α mRNA 表达水平显著升高（P＜0.01，P＜0.001），MyD88、 p-ERK/ERK、TNF-α 蛋白表达水平均明显升高（P＜0.05，P＜0.01，P＜0.001），NF-κB 入核细胞数占比显著 升高（P＜0.001）。与模型组比较，大黄素组大鼠的神经功能评分明显降低（P＜0.05），脑梗死面积明显缩小 （P＜0.05）；缺血半暗带皮质区的神经元数量及形态得到一定程度恢复；脑组织中 MyD88、TNF-α mRNA 表达 水平均明显降低（P＜0.05，P＜0.01），MyD88、p-ERK/ERK、TNF-α 蛋白表达水平均明显降低（P＜0.05）， NF-κB 入核细胞数占比显著降低（P＜0.001）。结论 大黄素对局灶性脑缺血大鼠具有预防保护作用，可能与 其抑制 MyD88 活化、ERK 磷酸化及 NF-κB 核移位，进而下调炎症级联反应及 TNF-α 等促炎因子分泌，从而 发挥抗炎作用有关。

Objective To investigate the effect and mechanism of emodin on focal cerebral ischemia in rats based on myeloid differentiation factor 88（MyD88）/extracellular signal-regulated kinase（ERK） pathway and nuclear factor-κB （NF-κB）nuclear translocation. Methods SD rats were randomly divided into sham operation group，model group and emodin group， with six rats in each group. The rat model of transient middle cerebral artery occlusion （tMCAO） was established by middle cerebral artery embolization. Rats in the emodin group were given 40 mg·kg-1 emodin by gavage for three times at 72， 48 and 24 hours before modeling. At 24 hours after modeling， the neurological function of rats was scored. TTC staining was used to detect the area of cerebral infarction. HE staining was used to observe the morphological changes of brain tissue. The mRNA expression levels of MyD88 and tumor necrosis factor- α （TNF- α）in brain tissue were detected by RT-qPCR. The expression levels of MyD88，ERK， p-ERK and TNF- α in brain tissue were detected by Western Blot. The protein expression of NF- κB in brain tissue was detected by immunofluorescence. Results Compared with the sham operation group， the neurological function score of the model group was significantly increased （P＜0.01）， and the cerebral infarction area was significantly increased （P＜0.01）. In the cortical area of the ischemic penumbra， cell necrosis， abnormal cell morphology， nuclear fragmentation and atrophy， and the number of cells decreased significantly； the mRNA expression levels of MyD88 and TNF- α in brain tissue were significantly increased （P＜0.01，P＜0.001），the protein levels of MyD88，p-ERK/ERK and TNF-α were significantly increased （P＜0.05，P＜0.01，P＜0.001）， and the proportion of NF- κB into nuclear cells was significantly increased （P＜0.001）. Compared with the model group，the neurological function score of rats in the emodin group was significantly decreased （P＜0.05），and the area of cerebral infarction was significantly reduced （P＜0.05）. The number and morphology of neurons in the ischemic penumbra cortex were restored to a certain extent. The mRNA expression levels of MyD88 and TNF-α in brain tissue were significantly decreased （P＜0.05， P＜0.01）， the protein levels of MyD88， p-ERK/ERK and TNF-α were significantly decreased （P＜0.05），and the proportion of NF- κB into nuclear cells was significantly decreased （P＜0.001）. Conclusion Emodin has a preventive and protective effect on rats with focal cerebral ischemia，which may be related to its inhibition of MyD88 activation，ERK phosphorylation and NF- κB nuclear translocation，and then down-regulation of inflammatory cascades and secretion of pro-inflammatory factors such as TNF-α，thereby exerting anti-inflammatory effects.

R285.5

广州市科技局市院联合资助项目（202201020506）；省部共建中医湿证国家重点实验室专项（SZ2022KF22，SZ2021ZZ46）；广东省中医 急症重点实验室专项（2019KT1340）