摘要
目的探讨基于核因子E2相关性因子2(Nrf2)/NOD样受体热蛋白结构域3(NLRP3)/半胱氨酸蛋白酶-1(caspase-1)信号通路探讨毛兰素(Eri)对脑缺血再灌注(I/R)损伤大鼠神经元焦亡的影响。方法通过线栓法建立脑I/R大鼠模型;将造模后的大鼠随机分为I/R组、Eri 5 mg·kg^(-1)组、Eri 10 mg·kg^(-1)组、Eri 20 mg·kg^(-1)组(各组给予不同剂量Eri灌胃)、阳性药(10 mg·kg^(-1)依达拉奉)组、Eri 20 mg·kg^(-1)+ML38530 mg·kg^(-1)(Eri+ML385组),另设假手术组(仅分离不结扎),各组均n=10只。用Zea Longa评分法评估大鼠神经行为;分离脑组织,检测ROS、IL-1β、IL-18水平;苏木精-伊红、碘化丙啶(PI)染色检测病理变化及神经元焦亡率;用qRT-PCR、Western blot法检测Nrf2、HO-1 mRNA表达及NLRP3、caspase-1、GSDMD、ASC蛋白表达。结果与假手术组比较,I/R组Zea Longa评分、IL-1β、IL-18、ROS水平、神经元焦亡率、NLRP3、caspase-1、GSDMD、ASC蛋白表达显著增加,Nrf2 mRNA、HO-1 mRNA表达显著降低(均P<0.05);经不同剂量Eri、阳性药干预后,Zea Longa评分、IL-1β、IL-18、ROS水平、神经元焦亡率、NLRP3、caspase-1、GSDMD、ASC蛋白表达显著降低,Nrf2 mRNA、HO-1 mRNA表达显著增加(均P<0.05);Eri+ML385组Zea Longa评分、IL-1β、IL-18、ROS水平、神经元焦亡率、NLRP3、caspase-1、GSDMD、ASC蛋白表达较Eri 20 mg·kg^(-1)组疗效显著增加,但Nrf2 mRNA、HO-1 mRNA表达显著降低(均P<0.05)。结论Eri可降低I/R大鼠神经元焦亡率,可能与上调Nrf2、抑制NLRP3/caspase-1表达有关。
Aim To investigate the effect of Erianin(Eri)on cell apoptosis in cerebral ischemia-reperfusion injury(I/R)rats based on the nuclear factor erythroid-2-related factor 2(Nrf2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteine protease-1(caspase-1)pathway.Methods A I/R rat model was established by blocking blood flow with thread occlusion method.After modeling,the rats were randomly separated into I/R group,Eri 5 mg·kg^(-1),Eri 10 mg·kg^(-1),Eri 20 mg·kg^(-1)groups(different doses of Eri administered intragastric),positive drug(10 mg·kg^(-1)edaravone)group,Eri(20 mg·kg^(-1))+ML385(30 mg·kg^(-1))group,with a sham surgery group(separated only without ligation),n=10 in each group.The neurological behavior of the rats was evaluated using the Zea Longa score.Brain tissue was isolated and ROS,IL-1βand IL-18 levels were detected.HE and propyl iodide(PI)staining were used to detect the pathological changes and neuronal pyroptosis rate.QRT-PCR and Western blot were applied to detect Nrf2,HO-1 mRNA expression,and NLRP3,caspase-1,GSDMD,and ASC protein expression.Results Compared with the sham surgery group,the Zea Longa score,IL-1β,IL-18,ROS levels,neuronal pyroptosis rate,the expression of NLRP3,caspase-1,GSDMD,and ASC proteins in I/R group were greatly increased,the expression of Nrf2 mRNA and HO-1 mRNA was greatly reduced(all P<0.05).After intervention with different doses of Eri and positive drugs,the Zea Longa score,IL-1β,IL 18,ROS levels,neuronal pyroptosis rate,and the expression of NLRP3,caspase-1,GSDMD,and ASC proteins were greatly reduced,the expression of Nrf2 mRNA and HO-1 mRNA was greatly increased(all P<0.05).In the Eri+ML385 group,Zea Longa score,IL-1β,IL-18,ROS levels,neuronal pyroptosis rate,NLRP3,caspase-1,GSDMD,and ASC protein expression were significantly increased in efficacy compared with the Eri 20 mg·kg^(-1)group,but Nrf2 mRNA and HO-1 mRNA expression were significantly decreased(all P<0.05).Conclusion Eri can reduce neuronal pyroptosis rate in I/R rats,which may be related to up-regulation of Nrf2 and inhibition of NLRP3/caspase-1 expression.
作者
朱超霞
李志营
吕晓飞
赵倩
程宝仓
杨会杰
周丽平
曾利敏
ZHU Chao-xia;LI Zhi-ying;LÜXiao-fei;ZHAO Qian;CHENG Bao-cang;YANG Hui-jie;ZHOU Li-ping;ZENG Li-min(Department of Neurologyy,the 7th People’s Hospital of Zhengzhou,Zhengzhou 450016,China;Department of Neurosurgery,the 7th People’s Hospital of Zhengzhou,Zhengzhou 450016,China)
出处
《中国临床神经科学》
2025年第2期128-135,共8页
Chinese Journal of Clinical Neurosciences
基金
河南省医学科技攻关计划联合共建项目(编号:LHGJ20230741)。
