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姜黄素对细菌性脑膜炎新生大鼠神经损伤的影响及机制
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| 篇名： | 姜黄素对细菌性脑膜炎新生大鼠神经损伤的影响及机制 |
| TITLE： | Effects and mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis |
| 摘要： | 目的 基于信号转导及转录活化因子1（STAT1）/核苷酸结合结构域富含亮氨酸重复序列和含热蛋白结构域受体3（NLRP3）信号通路，探讨姜黄素对细菌性脑膜炎新生大鼠神经损伤的影响及潜在机制。方法将雌雄各半的新生SD大鼠随机分为对照组（control组）、模型组（model组）、姜黄素低剂量组（Cur-L组）、姜黄素中剂量组（Cur-M组）、姜黄素高剂量组（Cur-H组）和姜黄素高剂量+STAT1转录增强剂[2（-1，8-萘啶-2-基）苯酚]组（Cur-H+2-NP组），每组15只。除control组外，其余各组大鼠经小脑延髓池注射B族链球菌菌悬液（1×104cfu/mL，10μL）构建细菌性脑膜炎模型。造模成功后，Cur-L、Cur-M、Cur-H组大鼠腹腔注射姜黄素1.25、2.5、5mg/kg，Cur-H+2-NP组大鼠腹腔注射姜黄素5mg/kg和2-NP0.5mg/kg，每天1次，连续3周。末次给药后，进行改良Loeffler评分，检测其脑脊液中白细胞（WBC）计数及炎症因子[肿瘤坏死因子α、白细胞介素6（IL-6）、IL-1β、IL-18]含量、脑含水量及血脑屏障通透性，观察其海马/皮质组织的病理改变，检测其海马/皮质组织凋亡细胞百分比、离子钙结合衔接分子1（Iba-1）阳性表达及Iba-1、NLRP3共定位情况以及STAT1/NLRP3信号通路相关蛋白（磷酸化STAT1、NLRP3、凋亡相关斑点样蛋白、焦孔素D、胱天蛋白酶1、IL-1β、IL-18）的表达情况。结果与control组比较，model组大鼠海马/皮质组织神经元形态明显异常，伴神经元水肿坏死、炎症细胞浸润等病理改变；其改良Loeffler评分、尼氏小体数均显著降低/减少，WBC计数和炎症因子含量、脑含水量、血脑屏障通透性、HE染色评分、退化神经元数、凋亡细胞百分比、Iba-1阳性表达、Iba-1和NLRP3共定位阳性细胞百分比、通路相关蛋白的表达均显著升高/增多/上调（P＜0.05）；与model组比较，姜黄素各剂量组大鼠海马/皮质组织病理改变均有所缓解，各定量指标均显著改善（P＜0.05）；而2-NP可显著逆转姜黄素对各定量指标的改善作用（P＜0.05）。结论姜黄素可改善细菌性脑膜炎新生大鼠脑水肿及血脑屏障损伤，减轻神经炎症，抑制细胞凋亡和焦亡，进而缓解神经损伤，其机制可能与抑制STAT1/NLRP3信号通路有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway. |
| 期刊： | 2026年第37卷第01期 |
| 作者： | 李月云；王艳蕊；付艳 |
| AUTHORS： | LI Yueyun，WANG Yanrui，FU Yan |
| 关键字： | 姜黄素；细菌性脑膜炎；神经炎症；细胞凋亡；细胞焦亡；STAT1/NLRP3信号通路；新生大鼠 |
| KEYWORDS： | curcumin； bacterial meningitis； neuroinflammation； cell apoptosis； cell pyroptosis； STAT1/NLRP3 signaling |
| 阅读数： | 71 次 |
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