CAJ | 학술논문

目的研究鱼藤酮对不同月龄SD大鼠多巴胺能神经元的影响及其机制.方法 3、12、20月龄雄性SD大鼠各40只,按照随机数字表法分为自然增龄组和鱼藤酮处理组,每组20只.自然增龄组皮下注射无鱼藤酮的混合溶剂,处理组皮下注射鱼藤酮[1.0 mg/(kg·d)],连续给药30d,每周停药1d,构建大鼠鱼藤酮染毒模型.大鼠黑质切片采用酪氨酸羟化酶(TH)免疫组化染色；测定黑质组织匀浆超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性；Western blotting检测黑质部位caspase-3表达水平.结果鱼藤酮处理后各月龄大鼠TH阳性细胞计数均比相应自然增龄组降低,且20月龄大鼠降低最为明显,差异均有统计学意义(P＜0.05).自然增龄组3月龄大鼠黑质组织SOD和CAT活性最高,20月龄大鼠有所下降,而鱼藤酮处理后各月龄大鼠SOD、CAT活性均明显增加,差异有统计学意义(P＜0.05).Western blotting结果显示,鱼藤酮处理组各月龄大鼠剪切活化的caspase-3的表达较自然增龄组均明显增加,差异有统计学意义(P＜0.05),其中20月龄大鼠最为明显.结论鱼藤酮可诱导大鼠TH阳性细胞随年龄增加而减少,氧化应激水平的增高和caspase-3的激活可能参与了SD大鼠对鱼藤酮敏感性随年龄增加的作用机制.
목적 연구어등동대불동월령SD대서다파알능신경원적영향급기궤제.방법 3、12、20월령웅성SD대서각40지,안조수궤수자표법분위자연증령조화어등동처리조,매조20지.자연증령조피하주사무어등동적혼합용제,처리조피하주사어등동[1.0 mg/(kg·d)],련속급약30d,매주정약1d,구건대서어등동염독모형.대서흑질절편채용락안산간화매(TH)면역조화염색；측정흑질조직균장초양화물기화매(SOD)화과양화경매(CAT)활성；Western blotting검측흑질부위caspase-3표체수평.결과 어등동처리후각월령대서TH양성세포계수균비상응자연증령조강저,차20월령대서강저최위명현,차이균유통계학의의(P＜0.05).자연증령조3월령대서흑질조직SOD화CAT활성최고,20월령대서유소하강,이어등동처리후각월령대서SOD、CAT활성균명현증가,차이유통계학의의(P＜0.05).Western blotting결과현시,어등동처리조각월령대서전절활화적caspase-3적표체교자연증령조균명현증가,차이유통계학의의(P＜0.05),기중20월령대서최위명현.결론 어등동가유도대서TH양성세포수년령증가이감소,양화응격수평적증고화caspase-3적격활가능삼여료SD대서대어등동민감성수년령증가적작용궤제.
Objective To investigate the influence of rotenone neurotoxin on dopaminergic neurons from SD rats of different months and its mechanism.Methods Forty 3-month-old,4012-month-old and 40 20-month-old SD rats were chosen in our study and equally randomized into control group and rotenone treatment group,respectively(n=20); rotenone(1.0 mg/[kg·d])was given to the rats in the rotenone treatment group for 30 consecutive d(having drug withdrawal 1 d per week)to induce rotenone neurotoxin models.Tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta(SNpc)was observed.Levels of total superoxide dismutase(SOD)and catalase(CAT)were determined by colorimetric method and protein level of caspase-3 was determined by Western blotting.Results A significant decreased number of TH-positive cells in 3-,12-and 20-month-old rats of rotenone treatment group was noted as compared with that in the control group,respectively(P＜0.05),and 20-month-old rats had the fewest number.SOD and CAT activities in 3 month-old rats of the control group enjoyed the highest level and decreased trend was noted in 20 month-old rats of the control group;as compared with those in the control group,the SOD and CAT activities in all the rats of rotenone treatment group increased significantly(P＜0.05).Western blotting revealed that the expression of cleaved caspase-3 in all the rats of rotenone treatment group obviously increased as compared with those in the control group,and 20-month-old rats showed the highest level of active caspase-3.Conclusion Rotenone can induce the decrease of TH-positive cell level following the increase of rat age; increase levels ofcaspase-3 and oxidative stress may take part in the mechanism of high sensibility of old SD rats to rotenone.