CAJ | 학술논문

目的探讨三七皂苷Rg1抗衰老的分子机制.方法 90只SD大鼠随机分为假手术组、模型组和治疗组.采用侧脑室注射β淀粉样蛋白1-42(Aβ_(1-42))联合腹腔注射D-半乳糖(D-gal)构建SD大鼠衰老模型,并同时给予三七皂苷Rg1预防性治疗,采用Morris水迷宫实验(MWM)进行行为学检测,用化学比色法检测大脑皮质谷胱甘肽还原酶(GR)和谷胱甘肽过氧化物酶(GSH-Px)的含量.用免疫组织化学法和免疫印迹法检测大脑皮质中Caspase-3前体蛋白和Bcl-2的含量. 结果　衰老模型组与假手术组比较:逃避潜伏期明显延长(P<0.05),在第Ⅲ象限逗留的时间明显减少(P<0.05),跨越平台次数明显减少(P<0.05),皮质GR和GSH-Px的含量降低(P<0.05),Caspase-3前体蛋白阳性神经元数明显减少(P<0.05),Caspase-3前体蛋白活化切割增加(P<0.05);而三七皂苷Rg1治疗后:大鼠逃避潜伏期明显缩短(P<0.05),在第Ⅲ象限逗留的时间明显增加(P<0.05),跨越平台次数明显增加(P<0.05),皮质GR 和GSH-Px的含量升高(P<0.05),Caspase-3前体蛋白阳性神经元数明显增加(P<0.05),Caspase-3前体蛋白活化切割减少(P<0.05).而Bcl-2阳性神经元数及表达在3组之间没有显著差异(P>0.05). 结论三七皂苷Rg1能通过上调衰老模型大鼠皮质内源性巯基抗氧化物(酶)GR 和GSH-Px的含量,抑制凋亡相关蛋白Caspase-3前体蛋白的活化切割而改善学习记忆能力,对抗大鼠神经系统衰老.
목적 탐토삼칠조감Rg1항쇠로적분자궤제.방법 90지SD대서수궤분위가수술조、모형조화치료조.채용측뇌실주사β정분양단백1-42(Aβ_(1-42))연합복강주사D-반유당(D-gal)구건SD대서쇠로모형,병동시급여삼칠조감Rg1예방성치료,채용Morris수미궁실험(MWM)진행행위학검측,용화학비색법검측대뇌피질곡광감태환원매(GR)화곡광감태과양화물매(GSH-Px)적함량.용면역조직화학법화면역인적법검측대뇌피질중Caspase-3전체단백화Bcl-2적함량. 결과　쇠로모형조여가수술조비교:도피잠복기명현연장(P<0.05),재제Ⅲ상한두류적시간명현감소(P<0.05),과월평태차수명현감소(P<0.05),피질GR화GSH-Px적함량강저(P<0.05),Caspase-3전체단백양성신경원수명현감소(P<0.05),Caspase-3전체단백활화절할증가(P<0.05);이삼칠조감Rg1치료후:대서도피잠복기명현축단(P<0.05),재제Ⅲ상한두류적시간명현증가(P<0.05),과월평태차수명현증가(P<0.05),피질GR 화GSH-Px적함량승고(P<0.05),Caspase-3전체단백양성신경원수명현증가(P<0.05),Caspase-3전체단백활화절할감소(P<0.05).이Bcl-2양성신경원수급표체재3조지간몰유현저차이(P>0.05). 결론 삼칠조감Rg1능통과상조쇠로모형대서피질내원성구기항양화물(매)GR 화GSH-Px적함량,억제조망상관단백Caspase-3전체단백적활화절할이개선학습기억능력,대항대서신경계통쇠로.
Objective In order to investigate anti-ageing mechanisms of the notoginsenoside Rg1,we used Aβ_(1-42) and D-galactose to establish aging rat model. Methods Ninety rats were divided into three groups at random: sham group, model group, treatment group. Aging rat models were established by injecting peritoneally D-galactose (100 mg/kg) to the rats for 56 days and after 35 days aggregated Aβ_(1-42)(μg) was injected to the right lateral ventricle of rats. Meantime, rats were treated by intragastric administration the notoginsenoside Rg1. Then spatial memory of experimental rats was examined with the Morris water maze(MWM). The thiol antioxidants including glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities were examined by colorimetric method. The concentration of the pro-caspase-3 and Bcl-2 were examined by the immunohistochemistry and Western blotting method. Results In aging model rats escape latercies were significantly prolonged (P<0.05), while decreases were seen in the time of staying the third quadrants of platform, the number of crossing over a platform, the concentration of the GR, GSH-Px, and pro-caspase-3 as compared with the sham group(P<0.05). After treatment of the notoginsenoside Rg1, the aging model rats exhibited significant increases in the time of staying the third quadrants of platform, the number of crossing over a platform, the concentration of the GR, GSH-Px, and pro-caspase-3(P<0.05), while a decrease was observed in escape latercies as compared to control group(P<0.05). Moreover there was no significant difference in the expression of the Bcl-2(P>0.05). Conclusion The results from our study indicate that the notoginsenoside Rg1 could improve the oriented learning and memory capacity and prevent the neurodegeneration of central nervous systems in aging model rats by up-regulating the expression of the thiol antioxidants(including GR and GSH-Px) and resisting the cleavage of the pro-caspase-3.