机构地区:[1]三峡大学医学院,湖北宜昌443002 [2]三峡大学附属仁和医院,湖北宜昌443001
出 处:《中国实验方剂学杂志》2017年第19期140-144,共5页Chinese Journal of Experimental Traditional Medical Formulae
基 金:国家自然科学基金项目(81273895)
摘 要:目的:研究三七总皂苷(PNS)对自然衰老模型大鼠肝脏内质网应激相关因子葡萄糖调节蛋白78(GRP78),磷酸化真核翻译起始因子2α(p-e IF2α),磷酸化PKR样内质网调节激酶(p-PERK)以及炎症相关因子磷酸化核转录因子-κB(p-NF-κB),肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β)调节作用,探索PNS对衰老大鼠肝脏内质网应激介导炎症反应的保护机制。方法:将50只SPF级SD大鼠随机10只1组,分为5组。分别为青年组(9月龄),自然衰老组(24月龄),PNS低、中、高剂量组。从18月龄起,PNS组大鼠按低、中、高剂量分别灌胃给予10,30,60 mg·kg^(-1)的PNS,每周灌胃6日,停灌1日,直至24月龄。末次给药后禁食不禁水12 h,将老鼠处死,迅速取出肝脏,过液氮后置于-80℃冰箱保存。苏木素-伊红(HE)染色法观察不同组肝组织形态变化,蛋白免疫印迹法(Western blot)检测肝脏组织中内质网应激相关因子GRP78,p-e IF2α,p-PERK及炎症相关因子p-NF-κB,TNF-α,IL-1β的蛋白变化。结果:自然衰老大鼠肝脏与青年组相比内质网应激相关因子GRP78,p-e IF2α,p-PERK及炎症相关因子p-NF-κB,TNF-α,IL-1β蛋白含量有所上升(P<0.01),低剂量PNS灌胃大鼠肝脏变化不明显,中、高剂量PNS显著降低衰老大鼠肝脏内质网应激相关因子及炎症相关因子的蛋白表达(P<0.05,P<0.01)。结论:PNS有保护自然衰老大鼠肝脏内质网应激导致炎症的作用。Objective: To investigate the effects of Panax Notoginseng saponins (PNS) on endoplasmic reticulum stress factors of glucose regulated protein 78 ku (GRP78), phosphorylated eukaryotic translation initiation factor (p-eIF2α), phosphorylated PKR like endoplasmic reticulum regulating kinase (p-PERK) and inflammatory factors of phosphorylated nuclear factor-Kappa B (p-NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta(IL-1β) in liver tissues of natural aging rats, and explore the protective mechanism of PNS on the endoplasmic reticulum stress mediated inflammatory response in aging rats' livers. Method: The 50 SPF SD rats were randomly divided into youth group (9 months), natural aging groups (24 months), low-, medium-and high-dose PNS groups, n=10 in each group. PNS was given at 10, 30, 60 mg·kg^-1 respectively in PNS groups from 18 months old to 24 months old, 6 days a week by intragastric administration. The rats were executed 12 hours after the last medication(food fasting, but water was given), and their livers were taken out immediately and storedat -80℃refrigerator aftertreatment by liquid nitrogen. Hematoxylin-eosin (HE) staining was used to observe the morphological changes of liver tissues in different groups, and Western blot was used to detect the protein changes of endoplasmic reticulum stress related factors GRP78, p-eIF2α, p-PERK and inflammatory related factors p-NF-κB, TNF-α, IL-1β in liver tissues. Result: As compared with the young rats' livers, the contents of GRP78, p-eIF2α, p-PERK, p-NF-κB, TNF-α, and IL-1β in the natural aging rats' livers were increased (P〈0.01); the liver changes were not obvious in low-dose PNS group;the protein expression levels of endoplasmic reticulum stress related factors and inflammatory related factorsin livers were decreased significantly in middle-and high-dose PNS groups (P〈0.01, P〈0.05). Conclusion: PNS can protect the naturally aging rats from inflammation indu
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