目的 探究紫花前胡素调节多巴胺 D2 受体（Drd2）/αB-晶状体蛋白（Cryab）/核因子 κB（NF-κB）信号通路 对缺氧缺血性脑损伤（HIBD）新生大鼠的神经保护作用。方法 参照 Rice 法构建新生大鼠 HIBD 模型，将造模 成功的大鼠随机分为模型组、低剂量紫花前胡素组、高剂量紫花前胡素组、高剂量紫花前胡素+QNZ（Drd2/ Cryab/NF-κB 通路抑制剂）组，其中低、高剂量紫花前胡素组分别灌胃 10、25 mg·kg-1 紫花前胡素，高剂量紫 花前胡素+QNZ 组在灌胃 25 mg·kg-1紫花前胡素基础上立即腹腔注射 0.6 mg·kg-1 QNZ。选取同批新生大鼠 6 只 为假手术组（只分离左颈总动脉，缝合伤口，不做结扎和缺氧处理）。对各组新生大鼠进行 Longa 评分；检测各 组新生大鼠脑含水量；HE 染色法检测各组新生大鼠海马组织损伤；ELISA 法检测海马组织中单核细胞趋化蛋 白 1（MCP-1）、白细胞介素 1β（IL-1β）、一氧化氮合酶（iNOS）水平；Western Blot 法检测各组大鼠海马组织 Drd2、Cryab、NF-κB 蛋白的表达以及 NF-κB 的核易位情况；COIP 实验检测 Cryab 和 NF-κB 的相互作用。 结果 相比于假手术组，模型组 Longa 评分、脑含水量、MCP-1、IL-1β、iNOS、NF-κB（细胞核）水平明显升 高，Drd2、Cryab、NF-κB（总）、NF-κB（细胞质）蛋白表达下降（P＜0.05，P＜0.001），模型组细胞空泡化增加、 排列紊乱、存在水肿和坏死细胞现象。相比于模型组，低、高剂量紫花前胡素组 Longa 评分、脑含水量、 MCP-1、IL-1β、iNOS、NF-κB（细胞核）水平明显降低，Drd2、Cryab、NF-κB（总）、NF-κB（细胞质）蛋白表达 升高（P＜0.05、P＜0.01，P＜0.001），细胞排列紊乱、坏死细胞现象得到改善，其中水肿现象改善较为明显。 施加通路抑制剂则逆转上述现象。CIOP 实验结果表明，低、高剂量紫花前胡素组中 Cryab 和 NF-κB 结合作用 明显（P＜0.001），高剂量紫花前胡素+QNZ 组则降低 Cryab 和 NF-κB 结合作用（P＜0.001）。结论 紫花前胡素 处理能降低炎症反应和氧化应激反应，进而改善 HIBD 的神经保护功能，其作用机制可能是促进 Drd2/Cryab/ NF-κB 通路信号的转导，通过增强 Cryab 与 NF-κB 之间的结合作用减弱 NF-κB 的核易位实现的。

Objective To investigate the neuroprotective effect of decursin on neonatal rats with hypoxic-ischemic brain damage （HIBD） by regulating the dopamine receptor D2 （Drd2）/αB-crystalline protein （Cryab）/nuclear factor-κB （NF- κB） signaling pathway. Methods A neonatal rat HIBD model was constructed using the Rice method. The successfully modeled rats were stochastically grouped into model group， low- dose decursin group， high- dose decursin group，and QNZ （Drd2/Cryab/NF-κB pathway inhibitor） group. The low-dose decursin group and high-dose decursin group were orally administered with 10 and 25 mg·kg-1 decursin，respectively. The high-dose decursin+QNZ group was immediately intraperitoneally injected with 0.6 mg·kg-1 QNZ on top of the 25 mg·kg-1 decursin gavage. Six newborn rats from the same batch were selected as the sham operation group （only the left common carotid artery was isolated，the wound was sutured，and no ligation or hypoxia treatment was performed）. Newborn rats in each group were subjected to Longa score. The brain water content of newborn rats in each group was measured. HE staining was applied to detect hippocampus damage of neonatal rats in each group. ELISA was applied to detect the levels of monocyte chemoattractant protein-1 （MCP-1），interleukin-1β （IL-1β） and nitric oxide synthase （iNOS） in hippocampus. Western Blot was applied to detect the protein expressions of Drd2，Cryab，NF-κB and nuclear translocation of NF-κB in hippocampus of rats in each group. The COIP experiment was applied to detect the interaction between Cryab and NF- κB. Results Compared with the sham group，the Longa score，brain water content，MCP-1，IL-1β，iNOS， and NF-κB （nuclear） levels were prominently increased in the model group，the protein expressions of Drd2，Cryab， NF- κB （total）， and NF- κB （cytoplasmic） were decreased （P＜0.05 or P＜0.001）， the model group showed increased vacuolization， disordered arrangement， and the presence of edema and necrotic cells. Compared with the model group，the Longa score，brain water content，MCP-1，IL-1β，iNOS，and NF-κB （nucleus） levels were prominently decreased in the low-dose decursin group and high-dose decursin group，the protein expressions of Drd2， Cryab，NF-κB （total），and NF-κB （cytoplasmic） were increased （P＜0.05，P＜0.01 or P＜0.001），the disorder of cell arrangement and the phenomenon of necrotic cells were improved，with a more prominent improvement in edema. Pathway inhibitors reversed the above phenomenon. The CIOP experiment results showed that the binding of Cryab and NF- κB was prominent in the low-dose decursin group and high-dose decursin group （P＜0.001）， the high-dose decursin+QNZ group reduced the binding of Cryab and NF- κB （P＜0.001）. Conclusion Decursin treatment can reduce inflammatory and oxidative stress responses，thereby improving the neuroprotective function of HIBD. It may be achieved by promoting the transduction of Drd2/Cryab/NF-κB pathway signals，enhancing the binding between Cryab and NF-κB，and weakening the nuclear translocation of NF-κB.

R285.5

河北省医学科学研究课题计划项目（20240753）