目的  探讨川芎嗪（TMP）防治大鼠炎症反应与细胞凋亡的作用机制。   方法  选取180只健康雄性SD大鼠，将其随机分为假手术组（sham）、脑缺血/再灌注损伤组（CIRI）、尼莫地平组（N）和TMP组，TMP再分为低剂量组（L）、中剂量组（M）和高剂量组（H）3个亚组, CIRI组采用改良线栓法制备CIRI模型；TMP各组于术前30 min分别尾静脉注射5 mg/kg、10 mg/kg和30 mg/kg TMP进行干预，N组尾静脉注射尼莫地平（1 mg/kg）, sham组和CIRI组给予等剂量的生理盐水。各组SD大鼠于构建CIRI模型苏醒后立即进行神经功能缺损评分，同时各组再灌注24 h进行2,3,5-氯化三苯基四氮唑(TTC)染色、苏木精-伊红(HE)染色及尼氏(Nissl)染色检测顶叶皮质缺血半暗带形态变化；ELISA检测顶叶皮质白细胞介素（IL）-1β及IL-8的表达，TUNEL检测顶叶皮质中的神经细胞凋亡，免疫荧光染色法检测β-catenin的阳性细胞在顶叶皮质表达，Western blotting检测顶叶皮质Bax和Bcl-2的表达。   结果  与sham组相比，CIRI组神经功能缺损评分显著增高（P<0.01），HE与Nissl染色见神经细胞肿胀变性，部分呈空泡样改变，细胞核固缩深染，神经元数量减少（P<0.01），尼氏体数量显著减少（P<0.01）；炎症因子IL-1β和IL-8的浓度显著上升（P<0.01），凋亡细胞与β-连环蛋白（β-catenin）阳性细胞及其平均吸光度值均显著增多、增高（P<0.01）；Bcl-2蛋白表达下降，而Bax蛋白表达显著增加（P<0.01）。与CIRI组比较，N组及TMP干预组大鼠的神经功能缺损评分降低（P<0.01），HE及Nissl染色发现大神经元水肿减轻，少许神经元被破坏，神经元数量增多（P<0.01），尼氏体数增多（P<0.01）；炎症因子IL-1β和IL-8浓度显著下降（P<0.01）,凋亡细胞与β-catenin阳性细胞及平均吸光度值均显著减少（P<0.01）；Bcl-2蛋白表达增加，而Bax蛋白表达显著下降（P<0.01）；与N组比较，随着TMP浓度的递增，神经功能、炎症反应与神经元病理变化呈现量效关系（P<0.05）。   结论  TMP干预处理后可以减轻大鼠CIRI后神经功能缺损、神经元受损、组织水肿、炎症因子和细胞凋亡，其机制可能与抑制大鼠顶叶皮质区β-catenin蛋白表达有关。 

Objective  To explore the mechanism of tetramethylpyrazine (TMP) in preventing and treating inflammation and cell apoptosis in rats.    Methods  Totally 180 healthy male SD rats were selected and randomly divided into sham operation group (sham), cerebral ischemia reperfusion injury(CIRI) group,nimodipine group (nimodipine,N),and TMP subdivided into low-dose group (low). There were three subgroups: low-dose(L), medium dose (M), and high dose (H).In CIRI group a modified suture method  was used to prepare the CIRI model;each TMP group was given tail injection 30 minutes before surgery.Intervention was given by intravenous injection of 5 mg/kg,10 mg/kg,and 30 mg/kg TMP. N group was given tail vein injection of nimodipine (1 mg/kg), sham group and CIRI group were given the same dose of normal saline. SD rats in each group were scored for neurological deficits immediately after the CIRI model was constructed.At the same time, after 24 hours of reperfusion in each group,2,3,5-triphenyltetrazole chloride (TTC） staining, HE staining and Nissl staining were performed to detect the morphological changes of the parietal cortex ischemic penumbra;ELISA to detect the expression of IL-1β and IL-8 in the parietal cortex,TUNEL detects neuronal cell apoptosis in the parietal cortex, immunofluorescence detected the expression of β-catenin positive cells in the parietal cortex,and Western blotting detected the expression of Bax and Bcl-2 in the parietal cortex.    Results  Compared with the sham group,the neurological deficit score in the CIRI group was significantly higher(P<0.01).The HE and Nissl staining showed neuronal swelling and degeneration,some of which showed vacuole-like changes, pyknosis and deep staining of the nucleus, and a decrease in the number of neurons(P<0.01),the number of Nissl bodies was significantly reduced(P<0.01);the concentrations of inflammatory factors IL-1β and IL-8 increased significantly(P<0.01),apoptotic cells and β-catenin-positive cells and their average absorbance values both increased significantly(P<0.01);the expression of Bcl-2 protein decreased,while the expression of Bax protein increased significantly(P<0.01).Compared with the CIRI group,the neurological deficit scores of the rats in the N group and the TMP intervention group were reduced (P<0.01),HE and Nissl staining revealed that the edema of large neurons was reduced,a few nerve cells were destroyed,and the number of neurons increased(P<0.01),the number of Nissl bodies   ncreased (P<0.01);the concentration of inflammatory factors IL-1β and IL-8 decreased significantly(P<0.01),apoptotic cells and β-catenin-positive cells and the average absorbance value decreased significantly (P<0.01)the expression of Bcl-2 protein increased,while the expression of Bax protein decreased significantly(P<0.01);compared with group N,as the concentration of TMP increased,nerve function, inflammatory response,and neuronal pathological changes showed dose-effects relationship (P<0.05).    Conclusion  TMP intervention treatment can alleviate the neurological deficit,neuronal damage,tissue edema,inflammatory factors and cell apoptosis after CIRI in rats.The mechanism may be related to the inhibition of the expression of β-catenin protein in the parietal cortex of rats.