摘要
目的:探讨决明子水提物(AESC)对脑缺血/再灌注损伤(CIRI)大鼠的脑保护作用及对环鸟苷-腺苷合酶(cGAS)/干扰素基因的刺激物(STING)通路的影响。方法:制备大鼠CIRI模型,随机数字表法分为CIRI组、AESC低(500 mg·kg^(-1))、中(1000 mg·kg^(-1))、高(2000 mg·kg^(-1))剂量组、尼莫地平(NMDP)阳性对照组(20 mg·kg^(-1)),每组18只,另取18只作为假手术组。灌胃治疗2周后,红四氮唑(TTC)法测定脑梗死体积,苏木素伊红(HE)法观察皮层区组织病变,免疫荧光法检测活化小胶质细胞和变性神经元,试剂盒检测肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平,实时荧光定量PCR测定胞质中线粒体DNA(mtDNA)水平,Western blot法测定cGAS/STING通路蛋白表达。结果:假手术组皮层区神经细胞排列规则,无变性神经元,小胶质细胞较少;CIRI组皮层区神经细胞疏松、紊乱,有较多变性神经元和小胶质细胞;中、高剂量AESC干预后上述损伤明显好转。较于假手术组,CIRI组脑梗死体积、神经功能评分、IL-6和TNF-α水平、胞质mtDNA含量、p-STING/STING、cGAS蛋白水平显著增加(P<0.05);较于CIRI组,中、高剂量AESC均可使脑梗死体积、神经功能评分、IL-6和TNF-α水平、胞质mtDNA含量、p-STING/STING、cGAS蛋白水平显著降低(P<0.05);AESC高剂量组上述指标与阳性对照NMDP组相比,差异无统计学意义(P>0.05)。结论:AESC对CIRI大鼠神经炎性损伤具有一定改善作用,可能与抑制cGAS/STING通路介导的炎性反应有关。
Objective:To investigate the protective effects of aqueous extract of semen cassiate(AESC)on cerebral ischemia/reperfusion injury(CIRI)in rats and the influence on cyclic guanosine-adenosine synthase(cGAS)/stimulator of interferon gene(ST-ING)pathway.Methods:The CIRI model in rats was prepared and the rats were divided into CIRI group,AESC low(500 mg·kg1)-,medium(1000 mg·kg^(-1))and high(2000 mg·kg^(-1))dose groups,and nimodipine(NMDP)positive control group(20 mg·kg1)by random number table method,there were 18 rats in each group,and another 18 rats were used as the sham operation group.After 2 weeks of intragastric treatment,the red tetrazolium(TTC)method was used to determine the volume of cerebral infarction,hematoxylin-eosin(HE)method was used to observe the lesions of cortical tissues,immunofluorescence method was used to detect activated microglia and degenerated neurons,the kits were used to detect the levels of tumor necrosis factorα(TNF-α)and inter-leukin 6(IL-6),real-time fluorescent quantitative PCR was used to measure the level of mitochondrial DNA(mtDNA)in the cyto-plasm,and Western blot method was used to determine the protein expression of cGAS/STING pathway.Results:In the sham opera-tion group,the nerve cells in the cortex were arranged regularly,and there were no degenerated neurons and fewer microglia;in the CIRI group,the nerve cells in the cortex were loose and disordered with more degenerated neurons and microglia;the above-mentionedinjuries were improved significantly after 1000 and 2000 mg·kg^(-1) AESC intervention.Compared with those in the sham operationgroup,the cerebral infarction volume,neurological function score,IL-6 and TNF-αlevels,cytoplasmic mtDNA content,p-STING/ST-ING and cGAS protein levels in the CIRI group increased(P<0.05);compared with the CIRI group,1000 and 2000 mg·kg1 AESC could significantly reduce the cerebral infarction volume,neurological function score,IL-6 and TNF-αlevels,cytoplasmic mtDNA content,p-STING/STING and cGAS protein levels(P<0.05);compared with
作者
周云
屠思维
傅美香
Zhou Yun;Tu Siwei;Fu Meixiang(Department of Rehabilitation Medicine,Affiliated Hospital of Shaoxing University of Arts and Sciences,Zhejiang Shaoxing 312000,China;Department of Rehabilitation Medicine,Affiliated Hospital of Shaoxing University of Arts and Sciences;Department of Comprehensive Rehabilitation,Chang’an District,Affiliated Hospital of Shaoxing University of Arts and Sciences)
出处
《中国药师》
CAS
2021年第10期1823-1828,共6页
China Pharmacist
基金
浙江省医药卫生科研面上项目(编号:2018KY842)。
关键词
决明子水提物
脑缺血/再灌注损伤
线粒体DNA
环鸟苷-腺苷合酶
干扰素基因的刺激物
炎性反应
Aqueous extract of semen cassiate
Cerebral ischemia/reperfusion injury
Mitochondrial DNA
Cyclic guanosine-adenosine synthase
Stimulator of interferon gene
Inflammatory response
