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규칙적인 운동과 DL-α-lipoic acid 투여가 노화 유도시 해마의 BDNF, Caspase-3 그리고 Apoptosis에 미치는 영향

Effect of Regular Exercise and DL-α-Lipoic Acid Supplementation on BDNF, Caspase-3 proteins and Apoptosis in Aging-Induced Rat Hippocampus

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본 연구는 D-galatose(50mg/kg) 투여에 따른 노화유도시 규칙적인 운동과 DL-α-lipoic acid 투여가 노화유도쥐의 해마에서 MDA 농도, BDNF, Caspase-3 단백질과 Apoptosis를 억제하는 효과를 규명하였다. 이를 위해 SD계 흰쥐 32마리를 노화 통제군(A-con; n=8), 노화 운동군(A-ex; n=8), 노화 lipoic acid 투여군(A-ala; n=8) 그리고 운동과 lipoic acid 투여를 병행한 노화 복합처치군(A-ea; n=8)으로 각각 무선배정하였다. 운동군(A-ex) 에게는 점진적 과부하의 원리를 적용시켜 주5일, 8주간 규칙적인 운동을 실시하도록 하였으며, lipoic acid 투여군(A-ala)에게는 단위 체중당 100mg의 lipoic acid를 투여하였다. 또한 복합집단군(A-ea) 에게는 규칙적인 운동과 lipoic acid 투여를 병행시켰다. 그 후 8주간의 실험처치를 끝내고 실험동물의 해마를 채취하여 실험에 필요한 변인에 대해 분석하여 결과를 도출하였다. 먼저 MDA 농도를 살펴본 결과 운동군, lipoic acid 투여군 그리고 복합군의 MDA 농도가 통제군에 비해 유의하게 감소하는 것으로 나타났다. 또한 BDNF 단백질 발현은 운동군, lipoic acid 투여군 그리고 복합처치군에서 통제집단에 비해 유의하게 증가하는 것으로 나타났으며, Caspase-3 단백질 발현은 운동군, lipoic acid 투여군 그리고 복합처치군에서 유의하게 감소하는 것으로 나타났다. 더욱이 TUNEL assay를 통해 살펴본 apoptosis에서 운동군과 lipoic acid 투여군에서 유의하게 감소하는 것으로 나타났으며, 특히 운동과 lipoic acid 투여를 병행한 복합처치시 그 효과가 배가되는 것을 확인하였다. 이상의 결과를 종합해보면, 규칙적인 운동과 DL-α-lipoic acid의 섭취는 노화유도쥐의 해마 뉴런의 산화적 스트레스와 apoptosis를 억제함으로서, 해마의 기능저하를 예방하고 나아가 뇌질환을 예방하는데 긍정적인 효과가 있으며, 더욱이 이들의 병행은 그 효과를 배가시키는 것으로 나타났다.

Abstract

We investigated a combined effects of 8-week exercise training and DL-α-lipoic acid supplementation on biochemical makers of MDA, BDNF, Capase-3 and apoptosis in hippocampus of aging rats induced by D-galactose injection (50mg/kg dissolved in 0.1ml dilution water). The rats were ramdomly assigned to one of the following four groups (n=8 per group): 1) control group (A-con) 2) exercise training group (A-ex) 3) DL-⍺-lipoic acid supplementation group (A-ala) 4) exercise training with DL-⍺-lipoic acid supplementation group (A-ea). The exercise training program regime consisted of running on a treadmill at an increasing pace. DL-⍺-lipoic acid (100mg/kg) was supplemented orally every day for 8 weeks. MDA concentrations were significantly lower in the A-ex, A-ala, A-ea groups compared with A-con group. BDNF protein were significantly hegher in the A-ex, A-ala, A-ea groups compared with A-con group. Caspase-3 protein were significantly lower in the A-ex, A-ala, A-ea groups compared with A-con group. In addition apoptotic cell death were significantly lower in the A-ex, A-ala, A-ea groups compared with A-con group. These results suggest that regular exercise training with DL-⍺-lipoic acid supplementation can offer beneficial effects of preventing aging and hippocampal neuron secondary to oxidative stress and apoptosis in D-galactose induced aging rats.

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