紫花前胡素调节Drd2/Cryab/NF-κB信号通路对缺氧缺血性脑损伤新生大鼠的神经保护作用  

The Neuroprotective Effect of Decursin on Neonatal Rats with Hypoxic-Ischemic Brain Injury by Regulating Drd2/Cryab/NF-κB Signaling Pathway

作　　者：刘丹 孟莉 刘淑燕 许坤 董沙沙 杜桂梅[1] LIU Dan;MENG Li;LIU Shuyan;XU Kun;DONG Shasha;DU Guimei(Department of Neonatology,Harrison International Peace Hospital,Hengshui 053000 Hebei,China;Second Department of Ultrasonography,Harrison International Peace Hospital,Hengshui 053000 Hebei,China;First Department of Pediatrics,Yanshan County People′s Hospital,Cangzhou 061300 Hebei,China;Department of Nephrology,Baoding Fifth Kospital,Baoding 071052 Hebei,China)

机构地区：[1]哈励逊国际和平医院新生儿科,河北衡水053000 [2]哈励逊国际和平医院超声二科,河北衡水053000 [3]河北省盐山县人民医院儿一科,河北沧州061300 [4]保定市第五医院肾内科,河北保定071052

出　　处：《中药新药与临床药理》2025年第3期384-391,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：河北省医学科学研究课题计划项目(20240753)。

摘　　要：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�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(nucleu

关 键 词：紫花前胡素 多巴胺D2受体 αB-晶状体蛋白 核因子ΚB 缺氧缺血性脑损伤 大鼠 

分 类 号：R285.5[医药卫生—中药学]