1、清热熄风活血汤调控 JNK/p38 MAPK 信号通路改善脑梗死大鼠脑组织损伤的干预机制庄志江1张丽红2兰瑞3(1 河南中医药大学第一附属医院脑病二区，河南郑州450099;2 郑州大学附属肿瘤医院中西医结合科;3河南中医药大学第一附属医院脑病五区)摘要 目的基于氨基末端蛋白激酶(JNK)/丝裂原活化蛋白激酶 p38 抗体(p38 MAPK)信号通路探究清热熄风活血汤对脑梗死大鼠脑组织损伤的干预作用的机制。方法选取 30 只 SD 健康雄性大鼠，其中 10 只为正常组，其余 20 只建立脑梗死模型并分为脑梗死组、清热熄风活血汤组，对各组大鼠进行学习记忆能力、神经功能评价，检测各组大鼠脑组织梗死
2、面积、含水量，酶联免疫吸附试验检测 Th1/Th2 趋化因子、氧化应激、炎症反应指标水平，Western 印迹检测 JNK/p38 MAPK 通路蛋白相对表达量。结果脑梗死组、清热熄风活血汤组各时间点逃避潜伏期显著长于正常组，清热熄风活血汤组各时间点逃避潜伏期显著短于脑梗死组(P0.05);清热熄风活血汤组大鼠神经功能缺损(mNSS)评分显著低于脑梗死组(P0.05)。脑梗死组、清热熄风活血汤组脑含水量显著高于正常组，清热熄风活血汤组大鼠梗死面积、含水量均显著低于脑梗死组(P0.05)。与正常组比较，其他两组-干扰素(IFN-)水平较低，白细胞介素(IL)-2、IL-4、大鼠总抗氧化能力(TA
3、OC)、活性氧(OS)、细胞间黏附分子(ICAM)-1、IL-3 水平较高，差异有统计学意义(P0.05);与脑梗死组比较，清热熄风活血汤组 IFN-水平较高，IL-2、IL-4、TAOC、OS、ICAM-1、IL-3 水平较低，差异有统计学意义(P0.05)。与正常组比较，其他两组 p-JNK、p-p38 MAPK 表达较高，差异有统计学意义(P0.05);与脑梗死组比较，清热熄风活血汤组 p-JNK、p-p38 MAPK 表达较低，差异有统计学意义(P0.05)。结论使用清热熄风活血汤干预的脑梗死大鼠学习记忆能力、神经功能有效改善，脑梗死面积、含水量下降，脑组织氧化应激损伤、炎症反应较轻，
4、JNK/p38 MAPK 信号通路蛋白受到有效调控，进而减轻脑组织损伤，起到脑保护作用。关键词 脑梗死;清热熄风活血汤;脑损伤;脑保护;炎症反应中图分类号 285.5 文献标识码 A 文章编号 1005-9202(2023)03-0607-05;doi:10.3969/j.issn.1005-9202.2023.03.027基金项目:国家自然科学基金项目(81973618);河北省科技攻关项目(202102310172)第一作者:庄志江(1974-)，男，医学博士，副主任医师，主要从事中西医结合脑血管病研究。Intervention mechanism of Qingre Xifeng Huo
5、xue Decoction regulatingJNK/p38 MAPK signaling pathway to improve brain tissue injury in ratswith cerebral infarctionZHUANG Zhi-Jiang，ZHANG Li-Hong，LAN uiThe Second District，Department of Encephalopathy，the First Affiliated Hospital of Henan University of Traditional ChineseMedicine，Zhengzhou 450099
6、，Henan，China【Abstract】ObjectiveTo explore the intervention mechanism of Qingre Xifeng Huoxue Decoction on brain tissue injury in ratswith cerebral infarction based on amino terminal protein kinase(JNK)/mitogen activated protein kinase p38 antibody(p38 MAPK)sig-naling pathway Methods30 healthy male S
7、D rats were selected，10 were selected as normal group，the other 20 rats were estab-lished cerebral infarction model and divided into cerebral infarction group and Qingre Xifeng Huoxue Decoction group The learning andmemory ability and neural function of rats in each group were evaluated The infarct
8、area and water content of rats in each group weredetected Th1/Th2 chemokines，oxidative stress and inflammatory reaction indexes were detected by enzyme-linked immunosorbent as-say The relative expression of JNK/p38 MAPK pathway protein were detected by Western blot esultsThe escape latency at eachti
9、me point of rats in cerebral infarction group and Qingre Xifeng Huoxue Decoction group was significantly longer than that in normalgroup，and the escape latency at each time point of rats in Qingre Xifeng Huoxue Decoction group was significantly shorter than that incerebral infarction group(P0 05);th
10、e Neurological deficit(mNSS)score of rats in Qingre Xifeng Huoxue Decoction group was sig-nificantly lower than that in cerebral infarction group(P0 05)The brain water content of rats in cerebral infarction group and QingreXifeng Huoxue Decoction group was significantly higher than that in normal gr
11、oup，the infarct area and water content of rats in QingreXifeng Huoxue Decoction group were significantly lower than those in cerebral infarction group(P0 05)Compared with the normal706庄志江等清热熄风活血汤调控 JNK/p38 MAPK 信号通路改善脑梗死大鼠脑组织损伤的干预机制第 3 期group，the other groups had lower levels of-interferon(IFN-)and
12、higher levels of interleukin(IL)-2，IL-4，total antioxidant capac-ity(TAOC)in rats，reactive oxygen(OS)，intercellular adhesion molecule(ICAM)-1 and IL-3，the differences were statisticallysignificant(P0 05);compared with the cerebral infarction group，the Qingre Xifeng Huoxue Decoction group had higher l
13、evel of IFN-and lower levels of IL-2，IL-4，TAOC，OS，ICAM-1 and IL-3，the differences were statistically significant(P0 05)Comparedwith the normal group，the expressions of p-JNK and p-p38 MAPK in the other groups were higher，the differences were statistically sig-nificant(P0 05);compared with the cerebr
14、al infarction group，the expressions of p-JNK and p-p38 MAPK in the Qingre XifengHuoxue Decoction group were lower，the differences were statistically significant(P0 05)ConclusionsThe intervention of QingreXifeng Huoxue Decoction could effectively improve the learning and memory ability and neurologic
15、al function of rats with cerebral in-farction，decrease the area of cerebral infarction and water content，reduce the oxidative stress damage and inflammatory reaction ofbrain tissue，and effectively regulate the JNK/p38 MAPK signal pathway protein，so as to reduce the brain tissue damage and play aprot
16、ective role in the brain【Key words】Cerebral infarction;Qingre Xifeng Huoxue Decoction;Brain damage;Brain protection;Inflammatory reaction脑梗死即为缺血性脑卒中，在全部脑卒中类型中占比高达 85%左右，是临床最为常见的脑血管疾病1，2。据相关流行病学调查数据显示，中老年人群为脑梗死的高发群体，近年来我国人口老龄化现象不断加重，每年新增脑梗死病例数呈现连年上升趋势，引起广大专家学者的关注3，4。脑梗死具有发病急、严重程度高、致残、致死率高、预后差的特点，因此寻找一种安全有效的治疗手段对脑梗死治疗、预后改善具有重要意义5，6。有研究表示，西医手段治疗脑梗死，临床疗效并不十分理想，因此越来越多的专家学者致力于中医药治疗脑梗死的研究7。本研究设计实验，建立脑梗死大鼠模型，使用清热熄风活血汤进行干预，探究清热熄风活血汤干预效果及相关作用机制。1材料与方法1.1材料选取 30 只 SD 健康雄性大鼠(郑州大学动物研究院，使用许可证号:SYXK(豫)2018-000
