柴胡皂苷A通过抑制内质网应激信号通路减轻乌头碱中毒大鼠脑组织细胞凋亡的机制分析  

Mechanism of saikosaponin A in relieving brain tissue apoptosis in rats with aconitine poisoning by inhibiting endoplasmic reticulum stress signaling pathway

作　　者：李华 徐鹏 赵艳 雷艳青 LI Hua;XU Peng;ZHAO Yan;LEI Yanqing(Department of Emergency,Xiangyang First People’s Hospital Affiliated to Hubei Medical College,Xiangyang,Hubei 441000,China)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院急诊科,湖北襄阳441000

出　　处：《安徽医药》2022年第7期1301-1305,I0002,共6页Anhui Medical and Pharmaceutical Journal

摘　　要：目的 探讨柴胡皂苷A对乌头碱中毒大鼠脑组织细胞凋亡、内质网应激信号通路的影响。方法 自2018年10月至2019年7月,选取购自武汉大学中南医院动物实验中心SPF级健康雄性SD大鼠100只,随机数字表法分为对照组、模型组、干预组1、干预组2、干预组3,每组各20只。采取乌头碱(20μg/kg)尾静脉注射制备乌头碱中毒大鼠模型,干预组1、干预组2、干预组3分别注射不同剂量的胡皂苷A(5 mg·kg^(-1)·d^(-1)、10 mg·kg^(-1)·d^(-1)、20 mg·kg^(-1)·d^(-1)),模型组与对照组注射等剂量的生理盐水。观察各组大鼠干预后12 h、24 h脑组织的凋亡情况以及内质网应激信号通路相关蛋白水平变化。结果 干预12 h、24 h后,模型组超氧化物歧化酶(SOD)活性低于对照组,丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平高于对照组,模型组B细胞淋巴瘤-2(Bcl-2)蛋白表达[(0.29±0.05)、(0.18±0.0)]低于对照组[(0.84±0.07)、(0.86±0.06)],模型组凋亡率[(34.24±2.11)%、(54.65±4.68)%]、Bcl相关X蛋白(Bax)蛋白表达[(1.25±0.06)、(1.39±0.05)]、CCAAT/增强子结合蛋白同源蛋白(CHOP)蛋白表达[(0.98±0.08)、(1.26±0.06)]、葡萄糖调节蛋白78(GRP78)蛋白表达[(1.45±0.08)、(1.62±0.07)]高于对照组[凋亡率(2.33±1.03)%、(2.42±1.15)%,Bax蛋白表达(0.33±0.06)、(0.35±0.07),CHOP蛋白表达(0.54±0.06)、(0.53±0.05),GRP78蛋白表达(0.68±0.06)、(0.69±0.06)],差异有统计学意义(P<0.05)。干预12 h、24 h后,干预组1、干预组2、干预组3的SOD活性、Bcl-2蛋白表达高于模型组,MDA、TNF-α、IL-6含量、凋亡率和Bax、CHOP、GRP78蛋白表达低于模型组(P<0.05)。结论柴胡皂苷A可以降低乌头碱中毒大鼠脑组织凋亡及脑组织氧化应激反应,可能与抑制内质网应激信号通路有关。Objective To explore effects of saikosaponin A on brain tissue apoptosis and endoplasmic reticulum(ER) stress signaling pathway of rats with aconitine poisoning.Methods A total of 100 SPF-level healthy male SD rats from the animal experimental center of Zhongnan Hospital Affiliated to Wuhan University were enrolled between October 2018 and July 2019.According to random number table method,they were assigned into control group,model group,intervention 1 group,intervention 2 group and intervention 3 group,and 20 cases in each group.Aconitine poisoning rat models were prepared by tail vein injection of aconitine(20 μg/kg).The intervention1 group,intervention 2 group and intervention 3 group were injected with different doses of saikosaponin A(5 mg·kg^(-1)·d^(-1),10 mg·kg^(-1)·d^(-1),20 mg·kg^(-1)·d^(-1)) respectively,while model group and control group were injected with the same volume of normal saline.At 12 h and24 h after intervention,brain tissue apoptosis and changes in levels of ER stress signaling pathway related proteins in each group were observed.Results At 12 h and 24 h after intervention,activity of superoxide dismutase(SOD) in model group was lower than that in control group,and levels of malondialdehyde(MDA),tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were higher than those in control group.At 12 h and 24 h after intervention,levels of B-cell lymphoma/leukemia-2(Bcl-2) protein in model group were(0.29±0.05)and(0.18±0.0),which were lower than those in control group [(0.84±0.07),(0.86±0.06)].At 12 h and 24 h after intervention,apoptosis rates [(34.24±2.11)%,(54.65±4.68)%],Bcl-associated X protein(Bax) [(1.25±0.06),(1.39±0.05)],CCAAT enhancer binding protein homologous protein(CHOP) [(0.98±0.08),(1.26±0.06)] and glucose-regulated protein 78(GRP78) [(1.45±0.08),(1.62±0.07) ] in model group were higher than those in control group [apoptosis rate:(2.33±1.03)%,(2.42±1.15)%;Bax:(0.33±0.06),(0.35±0.07);CHOP:(0.54±0.06),(0.53±0.05);GRP78:(0.68±0.06),(0.69±0.06)],the differ

关 键 词：柴胡属 植物中毒 乌头碱 柴胡皂苷A 脑组织凋亡 内质网应激 

分 类 号：R285.5[医药卫生—中药学]