当前位置: X-MOL 学术Int. Immunopharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
6-Gingerol protects against cerebral ischemia/reperfusion injury by inhibiting NLRP3 inflammasome and apoptosis via TRPV1 / FAF1 complex dissociation-mediated autophagy
International Immunopharmacology ( IF 5.6 ) Pub Date : 2021-09-17 , DOI: 10.1016/j.intimp.2021.108146
Jing Luo 1 , Jialei Chen 2 , Changhong Yang 3 , Junyi Tan 4 , Jing Zhao 4 , Ning Jiang 1 , Yong Zhao 1
Affiliation  

Background

Our previous studies demonstrated that autophagy alleviates cerebral I/R injury by inhibiting NLRP3 inflammasome-mediated inflammation. 6-Gingerol, a phenolic compound extracted from ginger, was reported to possess potent antiapoptotic and anti-inflammatory activities and is associated with autophagy. However, the effects of 6-Gingerol in cerebral I/R injury have not been elucidated, and whether they involve autophagy-induced NLRP3 inflammasome inhibition remains unclear.

Methods

Adult male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, followed by reperfusion for 24 h. 6-Gingerol and 3-methyladenine (3-MA) were injected intraperitoneally, and si-TRPV1 was injected via the lateral ventricle. Cerebral infarct volume, brain edema, neurological deficits, HE and Nissl were used to evaluate the morphological and functional changes of brain tissue, respectively. TRPV1, FAF1, autophagy related (LC3II/I, P62, Beclin1), inflammation related (NLRP3, cleaved-caspase-1, caspase-1, cleaved-IL-1β, IL-1β, cleaved-IL-18, IL-18) and apoptosis related (Bcl-2, Bax, cleaved-caspase-3) proteins were assessed by Western blot, immunofluorescence staining and coimmunoprecipitation, respectively. Enzyme linked immunosorbent assay (ELISA) was used to evaluate the changes in the expression levels of interleukin-1 (IL-1β) and interleukin-18(IL-18), respectively. The degree of neuronal apoptosis was evaluated by TUNEL staining. Neuronal ultrastructure was examined by transmission electron microscopy.

Result

6-Gingerol treatment significantly reduced cerebral infarct volume, improved brain edema and neurological scores, and reversed brain histomorphological damage after I/R injury. In addition, 6-Gingerol significantly reduced NLRP3 inflammasome-derived inflammation and neuronal apoptosis and upregulated autophagy. The autophagy inhibitor 3-MA rescued the effects of 6-Gingerol on the NLRP3 inflammasome and apoptosis. Moreover, the findings illustrated that 6-Gingerol inhibited autophagy-induced NLRP3 inflammasome activation and apoptosis through the dissociation of TRPV1 from FAF1.

Conclusion

In brief, 6-Gingerol exerts antiapoptotic and anti-inflammatory effects via TRPV1/FAF1 complex dissociation-mediated autophagy during cerebral I/R injury. Therefore, 6-Gingerol may be an effective drug for the treatment of I/R injury.



中文翻译:

6-姜酚通过抑制 NLRP3 炎性体和通过 TRPV1 / FAF1 复合物解离介导的自噬细胞凋亡来预防脑缺血/再灌注损伤

背景

我们之前的研究表明,自噬通过抑制 NLRP3 炎性体介导的炎症来减轻脑 I/R 损伤。据报道,6-姜酚是一种从生姜中提取的酚类化合物,具有强大的抗细胞凋亡和抗炎活性,并与自噬有关。然而,6-姜酚在脑 I/R 损伤中的作用尚未阐明,它们是否涉及自噬诱导的 NLRP3 炎症小体抑制仍不清楚。

方法

成年雄性 Sprague-Dawley (SD) 大鼠接受大脑中动脉闭塞 (MCAO) 1 小时,然后再灌注 24 小时。腹膜内注射 6-姜酚和 3-甲基腺嘌呤 (3-MA),并通过侧脑室注射 si-TRPV1。脑梗死体积、脑水肿、神经功能缺损、HE和Nissl分别用于评价脑组织的形态和功能变化。TRPV1、FAF1、自噬相关(LC3II/I、P62、Beclin1)、炎症相关(NLRP3、cleaved-caspase-1、caspase-1、cleaved-IL-1β、IL-1β、cleaved-IL-18、IL-18 ) 和凋亡相关蛋白(Bcl-2、Bax、cleaved-caspase-3)分别通过蛋白质印迹、免疫荧光染色和共免疫沉淀法进行评估。酶联免疫吸附试验(ELISA)分别用于评估白细胞介素-1(IL-1β)和白细胞介素-18(IL-18)表达水平的变化。通过TUNEL染色评估神经细胞凋亡的程度。通过透射电子显微镜检查神经元超微结构。

结果

6-姜酚治疗显着减少了脑梗死体积,改善了脑水肿和神经学评分,并逆转了 I/R 损伤后的脑组织形态学损伤。此外,6-姜酚显着减少 NLRP3 炎性体衍生的炎症和神经细胞凋亡,并上调自噬。自噬抑制剂 3-MA 挽救了 6-姜酚对 NLRP3 炎性体和细胞凋亡的影响。此外,研究结果表明,6-姜酚通过 TRPV1 从 FAF1 的解离来抑制自噬诱导的 NLRP3 炎性体激活和细胞凋亡。

结论

简而言之,6-姜酚在脑 I/R 损伤期间通过 TRPV1/FAF1 复合物解离介导的自噬发挥抗细胞凋亡和抗炎作用。因此,6-Gingerol 可能是治疗 I/R 损伤的有效药物。

更新日期:2021-09-17
down
wechat
bug