三七总皂苷调控cGAS/STING/NF-κB通路对急性脑梗死大鼠炎症反应的影响  

Effect of Panax notoginseng saponins on cGAS/STING/NF-κB pathway and inflammatory response in rats with acute cerebral infarction

作　　者：吴艺帆 傅晨[2] 罗超琴 陈宝鑫[3] 鲁雨荍 巩颖[5] 刘雪梅[2] WU Yi-fan;FU Chen;LUO Chao-qin;CHEN Bao-xin;LU Yu-qiao;GONG Ying;LIU Xue-mei(Beijing University of Chinese Medicine,Beijing 100029,China;Experimental Center of Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 10078;No.2 Department of Encephalopathy,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078;Department of Scientific Research.,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078;Department of Pharmacy,Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学东方医院实验中心,北京100078 [3]北京中医药大学东方医院脑病二科,北京100078 [4]北京中医药大学东方医院科研处,北京100078 [5]北京中医药大学东方医院药学部,北京100078

出　　处：《北京中医药》2021年第10期1061-1065,共5页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81973788,81774250);北京市自然科学基金项目(7182099)。

摘　　要：目的探讨三七总皂苷对急性脑梗死大鼠cGAS/STING/NF-κB通路的影响及抗炎作用。方法 30只大鼠随机分为假手术组、MCAO模型组、三七总皂苷治疗组(0.15 g/kg),各10只。除假手术组外,余大鼠采用线栓法建立大脑中动脉缺血(MCAO)模型,其中三七总皂苷治疗组术后给予三七总皂苷灌胃处理,缺血1.5 h再灌注24 h后采用Garcia JH评分观察神经功能缺损程度。处死大鼠采集缺血周围皮层组织,Western Blot法检测cGAS、STING、NF-κB及其磷酸化蛋白表达,RT-PCR法检测iNOS基因表达,ELISA法检测TNF-α、IL-6水平。结果与假手术组比较,MCAO模型组大鼠Garcia JH神经功能缺损评分明显降低(P<0.01),cGAS、STING、p-NF-κB/NF-κB蛋白表达及TNF-α、IL-6水平和iNOS基因表达均显著升高(P<0.01);与模型组比较,三七总皂苷治疗组大鼠Garcia JH神经功能缺损评分增加(P<0.05),cGAS、STING、p-NF-κB/NF-κB蛋白表达及TNF-α、IL-6水平和iNOS基因表达均明显降低(P<0.05)。结论三七总皂苷可能通过调控cGAS/STING通路,抑制NF-κB诱导的炎症反应,减轻脑损伤,发挥脑保护作用。Objective To investigate the effect of Panax notoginseng saponins on cGAS/STING/NF-κB pathway and anti-inflammatory action in rats with acute cerebral infarction.Methods 30 rats were randomly divided into three groups: sham operation group, MCAO model group, and Panax notoginseng saponins treatment group(PNS,0.15 g/kg).There were 10 rats in each group.Except for the sham operation group, The middle cerebral artery ischemia(MCAO)model were established by using thread occlusion method in other three groups, in which Panax notoginseng saponins treatment group were given Panax notoginseng saponins after established MCAO model.After 1.5 h of ischemia and 24 h of reperfusion, the Garcia JH score was carried out to observe the degree of neurological deficit.The rats were sacrificed, and the peripheral cortex was collected.The protein expression of cGAS,STING,NF-κB phosphorylation and NF-κB were detected by Western Blot.The gene expression of iNOS was measured by RT-PCR,and the levels of TNF-α and IL-6 were detected by ELISA.Results Compared with the sham operation group, the Garcia JH neurological function scores were obviously reduced in the MCAO model group(P<0.01);the protein expression levels of cGAS,STING,and p-NF-κB/NF-κB and the levels of TNF-α and IL-6 and the gene expression level of iNOS were all significantly increased(P<0.01).Compared with the model group, the Garcia JH neurological function scores was increased in the Panax notoginseng saponins treatment group(P<0.05);the protein expression levels of cGAS,STING,p-NF-κB/NF-κB and the levels of TNF-α and IL-6 and the gene expression level of iNOS were all reduced(P<0.05).Conclusion Panax notoginseng saponins may inhibit NF-κB-induced inflammatory response by regulating the cGAS/STING signaling pathway and alleviate brain damage to play a protective effect.

关 键 词：脑梗死 急性脑缺血再灌注 cGAS/STING/NF-κB通路 炎症反应 三七总皂苷 大鼠 

分 类 号：R285.5[医药卫生—中药学]