竹节参总皂苷减轻衰老大鼠的神经细胞凋亡

The Total Saponins of Panax japonicus Improved the Apoptosis of Natural Aging Rats

本研究探讨竹节参总皂苷(saponins from Panax japonicus,SPJ)对自然衰老大鼠内质网应激相关蛋白的调节作用以及对神经细胞凋亡的干预作用。雄性SD大鼠随机分为6月龄组、24月龄组、SPJ低剂量组(10mg/kg)和高剂量组(30mg/kg)。Westernblot法检测大鼠皮层和海马内质网应激相关蛋白(GRP78、p-PERK、p-EIF2α、ATF4、ATF6、p-IRE1、XBP1)以及凋亡相关蛋白(p-JNK、CHOP、Bcl-2、Bax)表达变化。结果显示,与6月龄组相比,24月龄组皮层/海马组织中GRP78、p-PERK、p-EIF2α、ATF4、ATF6、p-IRE1、XBP1和Bcl-2/Bax蛋白表达分别下降了80%/59%、82%/78%、79%/77%、94%/74%、72%/66%、78%/81%、82%/71%和90%/92%,p-JNK/JNK、CHOP蛋白表达分别上升了1/1.72、3.33/1.33倍。给予不同剂量竹节参总皂苷干预后,均能明显上调内质网应激相关蛋白和Bcl-2/Bax的表达水平,下调促凋亡蛋白表达水平。研究结果表明,竹节参总皂苷能通过上调内质网应激相关蛋白以及抗凋亡蛋白的表达水平,下调促凋亡蛋白的表达,从而维持衰老大鼠脑组织的内质网稳态,减少神经细胞凋亡。

The purpose of this study was to investigate the regulation of saponins from Panax japonicus(SPJ)on endoplasmic reticulum stress-related proteins in natural aging rats and the intervention on neuronal apoptosis.Male SD rats were randomly divided into four groups:6-month old group,24-month old group and SPJ-treated groups with the doses of 10 mg/kg and 30 mg/kg.Western blot was used to detect the expression of endoplasmic reticulum stress-related proteins(GRP78,p-PERK,p-EIF2α,ATF4,ATF6,XBP1)and apoptosis-related proteins(p-JNK,CHOP,Bcl-2,Bax)in cerebral cortex and hippocampus of SD rats.The results showed that,compared with the 6-month old group,the protein expression levels of GRP78,p-PERK,p-EIF2α,ATF4,ATF6,p-IRE1,XBP1 and Bcl-2/Bax were noticeably reduced by 80%or 59%,82%or 78%,79%or 77%,94%or 74%,72%or 66%,78%or 81%,82%or 71%,90%or 92%in the cerebral cortex or hippocampus of 24-month old group rats,respectively.And,p-JNK/JNK and CHOP increased by 1 or 1.72,3.33 or 1.33 times,respectively.In addition,these changes were reversed after different dozes of SPJ treatment.In summary,SPJ treatment can maintain endoplasmic reticulum homeostasis in brain tissue by up-regulating the levels of endoplasmic reticulum stress-related proteins and anti-apoptosis proteins,and down-regulating levels of pro-apoptosis-related proteins,hence to reduce neuronal apoptosis of aging rats.