毛蕊花糖苷对内毒素性休克大鼠脑组织保护作用及对凋亡的影响
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摘要
目的探讨毛蕊花糖苷对内毒素性休克大鼠的脑保护作用及其作用机制。方法将SPF级SD大鼠60只,体重200-250 g,随机分为假手术组、内毒素性休克组、毛蕊花糖苷低剂量组、毛蕊花糖苷中剂量组、毛蕊花糖苷高剂量组,每组12只。尾静脉注射5 mg/kg脂多糖(LPS)制备大鼠内毒素性休克模型,治疗组于造模前灌胃给药30 mg/kg、60 mg/kg、120 mg/kg,分别于感染性休克发生后12 h及24 h处死大鼠。HE染色观察大鼠脑组织病理变化;检测脑组织含水量变化;检测脑组织中IL-1β, IL-6, TNF-α及IL-10水平;TUNEL法检测大鼠脑内细胞凋亡情况;Western Blot法检测各组大鼠脑组织中Bax、Bcl-2及Caspase-3蛋白表达水平。结果与LPS组相比,毛蕊花糖苷中、高剂量组大鼠脑组织炎性细胞浸润及细胞排列结构明显改善;脑组织含水量明显降低;脑组织IL-10水平升高,IL-1β, IL-6及TNF-α水平降低;神经细胞凋亡数量明显减少;凋亡相关蛋白Bax、Caspase-3表达降低,Bcl-2蛋白表达升高,且呈剂量依赖性。结论毛蕊花糖苷对内毒素性休克大鼠具有一定的脑保护作用,可能与其抗炎抗凋亡作用相关。
Objective To explore the protective effect and possible mechanism of acteoside on brain injury in LPS-induced septic shock rats. Methods Sixty SPF grade SD rats, weighing 200-250 g, were randomly divided into shamoperated group, septic shock group, acteoside low dose group, acteoside medium dose group and acteoside high dose group,each group 12 rats. Rats were injected intravenously with 5 mg/kg lipopolysaccharide(LPS) to establish the model of septic shock. Rats in actoside groups were intragastric administration with 30 mg/kg, 60 mg/kg, 120 mg/kgacteoside before model formation, and the rats were sacrificed at 12 h and 24 hafter septic shock. HE staining was used to observed the pathological changes of brain tissue; brain water content was tested; the level of IL-1β, IL-6, TNF-α and IL-10 in brain tissue was tested; TUNEL was used to analysis cell apoptosis; Western blot was used to detect the expression of apoptic proteins Bax,Bcl-2, Caspase-3. Results Compared to LPS group, inflammatory cell infiltration of brain was significantly improved in acteoside medium and high dose group, brain water content was reduced, the expression level of IL-10 was increased, the levels of IL-1β, IL-6 and TNF-α were decreased; the number of apoptotic cells were significantly decreased; the expression of Bax and caspase-3 protein was downregulated, Bcl-2 protein expression level was upregulated. Conclusion The therapeutic effect of Actoside on brain injury was related to reducing the infiltration of inflammatory cells and apoptotic cells in rats with septic shock.
Objective To explore the protective effect and possible mechanism of acteoside on brain injury in LPS-induced septic shock rats. Methods Sixty SPF grade SD rats, weighing 200-250 g, were randomly divided into shamoperated group, septic shock group, acteoside low dose group, acteoside medium dose group and acteoside high dose group,each group 12 rats. Rats were injected intravenously with 5 mg/kg lipopolysaccharide(LPS) to establish the model of septic shock. Rats in actoside groups were intragastric administration with 30 mg/kg, 60 mg/kg, 120 mg/kgacteoside before model formation, and the rats were sacrificed at 12 h and 24 hafter septic shock. HE staining was used to observed the pathological changes of brain tissue; brain water content was tested; the level of IL-1β, IL-6, TNF-α and IL-10 in brain tissue was tested; TUNEL was used to analysis cell apoptosis; Western blot was used to detect the expression of apoptic proteins Bax,Bcl-2, Caspase-3. Results Compared to LPS group, inflammatory cell infiltration of brain was significantly improved in acteoside medium and high dose group, brain water content was reduced, the expression level of IL-10 was increased, the levels of IL-1β, IL-6 and TNF-α were decreased; the number of apoptotic cells were significantly decreased; the expression of Bax and caspase-3 protein was downregulated, Bcl-2 protein expression level was upregulated. Conclusion The therapeutic effect of Actoside on brain injury was related to reducing the infiltration of inflammatory cells and apoptotic cells in rats with septic shock.
引文
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[10]邓海峰,孙缦利,陈浩,等.毛蕊花糖苷对抑郁症大鼠行为学和前额叶皮层内质网应激的影响[J].中国病理生理杂志,2018,34(1):101-106.
[2]Sanz D,D'Arco F,Robles CA,et al.Incidence and pattern of brain lesions in paediatric septic shock patients[J].Br J Radiol,2018,91(1084):20170861.
[3]邓海峰,孙缦利,吴琼,等.毛蕊花糖苷通过调控BDNF-TrkB信号通路改善CUMS大鼠的抑郁样行为[J].中国病理生理杂志,2018,34(9):1633-1637.
[4]邢海燕,苗鑫,张晓菲,等.BDNF乙酰化修饰参与毛蕊花糖苷对Aβ_(25-35)致PC12细胞损伤的保护作用[J].中国新药杂志,2018,27(16):1910-1917.
[5]苗鑫,张弘,武燕,等.肉苁蓉毛蕊花糖苷对D-半乳糖诱导PC12神经细胞损伤的保护作用[J].中国药学杂志,2017,52(23):2071-2078.
[6]赵红领,李磊,苗成.川芎嗪对内毒素性休克大鼠脑损伤的作用[J].中国病理生理杂志,2016,32(9):1708-1712.
[7]Korish AA,Arafa MM.Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock[J].Braz J Infect Dis,2011,15(4):332-338.
[8]胡航.毛蕊花糖苷对Aβ_(1-42)损伤神经元保护作用及机制研究[J].辽宁中医药大学学报,2016,18(10):34-37.
[9]宋小敏,廖理曦,董馨,等.毛蕊花糖苷抑制脂多糖诱导的BV-2小胶质细胞炎症反应及机制研究[J].中国中药杂志,2016,41(13):2506-2510.
[10]邓海峰,孙缦利,陈浩,等.毛蕊花糖苷对抑郁症大鼠行为学和前额叶皮层内质网应激的影响[J].中国病理生理杂志,2018,34(1):101-106.