基于NOD2/RIP2/NF-κB信号通路研究柚皮素对新生大鼠缺血缺氧性脑损伤的保护作用

Protective effects of naringenin against hypoxic-ischemic brain damage in neonatal rats through suppression of NOD2/RIP2/NF-κB pathway

目的探讨柚皮素对新生大鼠缺血缺氧性脑损伤的保护作用及其机制。方法 96只7日龄新生SD大鼠,随机分为4组,假手术组(Sham)、缺血缺氧性脑损伤组(HIBD)、柚皮素低剂量组(50 mg·kg^(-1))、柚皮素高剂量组(100 mg·kg^(-1))。术后48 h对各组新生大鼠进行神经功能缺陷评分,HE染色观察各组新生大鼠脑组织病理学改变,干湿重法检测各组新生大鼠脑含水量,免疫印迹法测定缺血缺氧侧脑组织NOD2、RIP2、NF-κB蛋白的表达,酶联免疫吸附法检测TNF-α、IL^(-1)β的水平。结果与模型组比较,柚皮素低、高剂量组神经行为学指标评分下降,病理学损伤减轻,新生大鼠脑含水量明显减少(P<0.05);Western blot检测显示,与模型组比较,柚皮素低、高剂量组新生大鼠脑组织NOD2、RIP2、NF-κB蛋白表达下调(P<0.05);ELISA检测显示,柚皮素低、高剂量组TNF-α和IL^(-1)β在脑组织中含量低于模型组(P<0.05)。结论柚皮素对新生大鼠缺血缺氧性脑损伤有保护作用,其机制可能与柚皮素下调NOD2、RIP2、NF-κB蛋白的表达,并减少TNF-α、IL^(-1)β的分泌有关。

Aim To explore the protective effects of naringin on hypoxic ischemic brain injury in neonatal rats and its mechanism. Methods Ninety-six healthy7-day neonatal SD rats were randomly divided into sham operation group,hypoxic-ischemic brain damage group（ HIBD group）,HIBD with low-dose naringenin group（ 50 mg · kg^（-1）,NG-L） and HIBD with highdose naringenin group（ 100 mg ·kg^（-1）,NG-H）. Neurological deficit,HE staining and brain water content were measured 48 h after operation. Immunoblotting was used to detect the expressions of NOD2,RIP2 and NF-κB. Enzyme linked immunosorbent assay（ ELISA）method was adopted to detect TNF-α and IL^（-1）β expression. Results Compared with HIBD group,the neurological deficit score decreased,the pathological damage was reduced,and the water content of brain tissues markedly decreased by naringenin（ 50,100 mg·kg^（-1）） treatment（ P〈 0. 05）. Western blot revealed the down-regulation of NOD2,RIP2 and NF-κB by naringenin（ 50,100 mg·kg^（-1）） treatment（ P〈 0. 05）.The content of TNF-α and IL^（-1）β in brain tissues was lower than that of HIBD group（ P 〈0. 05）. Conclusion Naringenin is likely to exert a protective role in neonatal rats of hypoxic ischemic brain injury perhaps through decreasing the expression of NOD2,RIP2 and NF-κB,and reducing the secretion of TNF-α and IL-1β.