桔皮素调控Nrf2/NQO1通路减轻脊髓损伤大鼠炎症与氧化应激损伤  

Tangeretin attenuating inflammatory and oxidative stress injury via Nrf2/NQO1 pathway in rats with spinal cord injury

作　　者：吴江林 高明 梁超伦 王凯 肖俊强[1,2] 梁家畅 林燕 Wu Jianglin;Gao Ming;Liang Chaolun;Wang Kai;Xiao Junqiang;Liang Jiachang;Lin Yan(Department of Orthopedics and Traumatology,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China;The Second Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510000,China;Geriatrics Department,Guangzhou Zengcheng District Traditional Chinese Medicine Hospital,Guangzhou 510000,China)

机构地区：[1]广州中医药大学第二附属医院骨伤科,广州510120 [2]广州中医药大学第二临床医学院,广州510000 [3]广州市增城区中医医院老年病科,广州510000

出　　处：《国际中医中药杂志》2024年第11期1462-1468,共7页International Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(82004384);广东省中医院拔尖人才科研专项(BJ2022KY07);广东省自然科学基金(2022A1515010793)。

摘　　要：目的研究桔皮素对脊髓损伤大鼠的修复作用及其机制。方法将大鼠按随机数字表法分为假手术组、模型组、桔皮素组,每组8只。除假手术组外,其余各组采用Allen打击法制作脊髓损伤大鼠模型。造模成功后,桔皮素组灌胃桔皮素50 mg/kg,假手术组及模型组灌胃等体积的生理盐水,1次/d,连续干预14 d。分别于造模后第0、3、7、14天,采用Basso-Beattie-Bresnahan(BBB)评分评估大鼠运动功能恢复情况;采用HE染色及Nissl染色观察脊髓组织形态学变化,使用ELISA法检测各组大鼠脊髓组织SOD、GSH活性和MDA、IL-1β、TNF-α、IL-10水平,免疫荧光法检测脊髓组织胶质纤维酸性蛋白(GFAP)和神经元核抗原(Neun)表达,Western blot法检测脊髓组织IL-1β、TNF-α、IL-10、核因子E2相关因子2(Nrf-2)和NAD(P)H-醌氧化还原酶1(NQO-1)表达。结果与模型组比较,桔皮素组大鼠BBB评分升高(P<0.05),HE染色评分降低(P<0.05),Nissl染色尼氏小体数增加(P<0.05);脊髓组织SOD、GSH活性及IL-10水平升高(P<0.05),MDA、IL-1β、TNF-α水平降低(P<0.05);GFAP荧光强度减弱(P<0.05),Neun荧光强度增强(P<0.05);IL-1β、TNF-α蛋白相对表达降低(P<0.05),IL-10、Nrf-2、NQO-1蛋白相对表达升高(P<0.05)。结论桔皮素可能通过Nrf2/NQO1信号通路发挥抗炎、抗氧化应激的作用,缓解大鼠早期的脊髓损伤;另一方面可能通过减少胶质瘢痕,促进神经细胞生成,从而促进脊髓损伤的恢复。Objective To explore the repairing effect and mechanism of tangeretin in rats with spinal cord injury.Methods The rats were divided into sham-operation group,model group and tangeretin group according to random number table,with 8 rats in each group.Except for the sham-operation group,Allen hit method was used to make rat models in the other groups.After the model was successfully established,the tangeretin group was intragastrically administered with tangeretin 50 mg/kg,and the sham-operation group and the model group were intragastrically administered with an equal volume of normal saline once a day for 14 days.On days 0,3,7,and 14 after modeling,the motor function recovery of rats was assessed using the Basso-Beattie-Bresnahan(BBB)score;the morphological changes of the spinal cord tissues were observed using HE staining and Nissl staining;the SOD and GSH activities and MDA,IL-1β,TNF-α,and IL-10 levels in the spinal cord tissues of rats in each group were measured using ELISA kit detection;the GFAP and Neun expressions in the spinal cord tissues were detected by immunofluorescence;the IL-1β,TNF-α,IL-10,nuclear factor E2-related factor 2(Nrf-2),and NAD(P)H-quinone oxidoreductase 1(NQO-1)expressions in the spinal cord tissues were detected by Western blot.Results Compared with the model group,the BBB score increased in the tangeretin group(P<0.05),HE staining score decreased(P<0.05),and the number of Nissl bodies increased(P<0.05);the level of IL-10,SOD and GSH activities increased(P<0.05),and IL-1β,TNF-αand MDA levels decreased in the spinal cord tissue(P<0.05);GFAP fluorescence intensity decreased(P<0.05)and NeuN fluorescence intensity increased(P<0.05);the relative expression of IL-1βand TNF-αdecreased(P<0.05),and the relative expressions of IL-10,Nrf-2 and NQO-1 protein increased(P<0.05).Conclusions Tangeretin can exert anti-inflammatory and anti-oxidative stress effects through the Nrf2/NQO1 signaling pathway and alleviate early spinal cord injury in rats.On the other hand,it may promote the recovery

关 键 词：脊髓损伤 桔皮素 炎症 氧化性应激 Nrf2/NQO1通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]