番茄碱对慢性脑缺血大鼠神经炎症的影响及可能机制  

Effect and its possible mechanism of tomatidine on neuroinflammation in rats with chronic cerebral hypoperfusion

作　　者：梁勇 白杨 熊剑 LIANG Yong;BAI Yang;XIONG Jian(Department of Neurosurgery,The General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院神经外科,辽宁沈阳110016

出　　处：《解剖科学进展》2024年第5期475-478,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金(82101318)。

摘　　要：目的探究番茄碱对慢性脑缺血大鼠神经炎症的作用及可能机制。方法50只SD大鼠随机分为假手术组(Sham组)、慢性脑缺血组(CCH组)、番茄碱低剂量组(TD-L组)、番茄碱中剂量组(TD-M组)和番茄碱高剂量组(TD-H组),每组10只,采用改良型永久性双侧颈总动脉结扎法建立CCH模型。Zea Longa评分评价大鼠神经功能;HE染色观察大鼠脑组织病理损伤;ELISA检测脑组织中TNF-α、IL-6和IL-1β含量;免疫荧光检测大鼠脑组织中小胶质细胞标志物IBA1阳性细胞数;Western blot检测大鼠脑组织中NLRP3、ASC、cleaved caspase1、p-JNK和p-c-JUN蛋白表达水平。结果番茄碱能降低慢性脑缺血大鼠神经缺损功能评分,改善大鼠脑组织病理损伤,降低脑组织中TNF-α、IL-6和IL-1β含量以及IBA1阳性细胞数,下调脑组织中NLRP3、ASC、cleaved caspase1、p-JNK和p-c-JUN蛋白表达水平。结论番茄碱抑制JNK/c-JUN信号通路介导的NLRP3炎症小体激活改善CCH大鼠脑损伤和神经炎症,并抑制脑组织中小胶质细胞激活。Objective To explore the effect and its possible mechanism of tomatidine on neuroinflammation in rats with chronic cerebral hypoperfusion.Methods 50 SD rats were randomly divided into sham operation group(Sham group),chronic cerebral hypoperfusion group(CCH group),low-dose group(TD-L group),medium-dose group(TD-M group)and high-dose group(TD-H group),with 10 rats in each group.CCH model was established by modified permanent bilateral common carotid artery ligation.Zea Longa score was used to evaluate the neurological function of rats.HE staining was used to observe the pathological damage of brain tissue in rats.ELISA was used to detect the contents of TNF-α,IL-6 and IL-1βin brain tissue.Immunofluorescence was used to detect the number of IBA1 positive cells in rat brain tissue.Western blot was used to detect the expressions of NLRP3,ASC,cleved caspase 1,p-JNK and p-c-JUN in brain tissue of rats.Results Tomatidine can reduce the nerve defect function score in rats with chronic cerebral hypoperfusion,improve the pathological injury in brain tissue of rats,reduce the contents of TNF-α,IL-6 and IL-1βand the number of IBA1 positi ve cells in brain tissue,down-regulate the expressions of NLRP3,ASC,cleaved caspase1,p-JNK,and p-c-JUN in brain tissue of rats.Conclusion Tomatidine can improve brain injury and neuroinflammation in CCH rats and inhibit the activation of microglia in brain tissue,and its mechanism may be related to inhibiting the activation of NLRP3 inflammatory corpuscles mediated by JNK/c-JUN signaling pathway.

关 键 词：慢性脑缺血 神经炎症 番茄碱 NLRP3炎症小体 JNK/c-JUN信号通路 

分 类 号：R743.31[医药卫生—神经病学与精神病学]