운동 강도가 Lipopolysaccharide에 의하여 유도된 저강도 전신염증 흰쥐 모델에서 Tumor Necrosis Factor-α와 Interleukin-6 발현에 미치는 영향

국문 초록 (Abstract)

본 연구의 목적은 lipopolysaccharide (LPS)에 의하여 유도된 저강도 전신염증 흰쥐 모델을 대상으로 유산소 운동 강도에 따른 혈청 및 뇌에서 종양 괴사 인자-알파와 인터루킨-6의 변화를 알아보고자 하였다. 본 실험에 사용된 동물은 Sprague-Dawley 수컷 흰쥐 45마리를 이용하였다. 실험동물은 open-field test 결과를 바탕으로 총 5개 군(각 군별 n=9)으로 배정하였다. 군의 구분은 대조군, LPS 투여군, LPS 투여 후 저강도 운동군, LPS 투여 후 중강도 운동군, LPS 투여 후 고강도 운동군으로 구성하였다. LPS 투여 후 트레드밀 운동은 경사도 0%에서 60분간 각 강도별로 일회실시하였다. 저강도 운동군은 8 m/min, 중강도 운동군은 14 m/min, 고강도 운동군은 22 m/min의 속도로 트레이드밀 달리기를 수행하였다. 본 실험의 결과 혈청의 종양 괴사 인자-알파(TNF-α)는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 운동군 모두에서 유의하게 감소하였다. 인터루킨-6(IL-6)는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 운동피질의 종양 괴사 인자-알파는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 모든 운동군에서 유의하게 감소하였다. 인터루킨-6는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 뇌실주위 신경핵에서의 종양 괴사 인자-알파는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 저강도, 중강도, 고강도 모든 운동군에서 유의하게 감소하였다. 인터루킨-6는 대조군과 비교하여 LPS 투여군에서 유의하게 증가하였으며, LPS 투여군과 비교하여 고강도 운동군에서 유의하게 증가하였다. 본 연구의 결과, LPS 투여는 혈청 및 뇌 운동피질과 뇌실주위 신경핵에서 종양 괴사 인자-알파와 인터루킨-6의 발현을 증가시켰다. 또한 LPS 투여 후 고강도 운동은 혈청 및 뇌 운동피질과 뇌실주위 신경핵에서 종양 괴사 인자-알파를 억제하고 인터루킨-6의 발현을 증가시켰다. 본 실험의 결과 고강도 운동은 만성 질환의 원인인 저강도 전신염증의 개선에 보다 효과적인 것으로 나타났다. 따라서 저강도 전신염증 개선을 위한 운동강도 설정에는 고강도 운동이 보다 효과적일 수 있는 것으로 생각된다.

다국어 초록 (Multilingual Abstract)

In the present study, we investigated the effect of exercise intensity on the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the rats with lipopolysaccharide-induced low-grade systemic inflammation. Forty-five male Sprague- Dawley rats were used for the present study. The animals were divided into five groups (n=9 in each group): control group, LPS-treated group, LPS-treated and low-intensity exercise group, LPS-treated and moderate-intensity exercise group, and LPS-treated and high-intensity exercise group. Each training session consisted of one bout of treadmill running for 60 min at 0 degree of inclination. The exercise load of low-intensity was at a speed of 8 m/min, moderate-intensity was at a speed of 14 m/min, and high-intensity was at a speed of 22 m/min. In the present results, the concentrations of TNF-α and IL-6 in the serum were increased by LPS injection. The expressions of TNF-α and IL-6 in the motor cortex and hypothalamic paraventricular nucleus were also increased by LPS injection. Treadmill exercise at all intensities suppressed LPS-induced TNF-α levels in the serum, motor cortex, and hypothalamic paraventricular nucleus. Treadmill exercise at high-intensity enhanced IL-6 levels in the serum, motor cortex, and hypothalamic paraventricular nucleus. Our present study showed that high-intensity treadmill exercise decreased TNF-α level and increased IL-6 level in the serum, motor cortex, and hypothalamic paraventricular nucleus of rats with LPS-induced low-grade systemic inflammation. These results suggest that treadmill exercise at high-intensity may be valuable strategy for overcoming the low-grade systemic inflammation. (Korean J Str Res 2010;18:201∼208)

목차 (Table of Contents)

• 서론
• 재료 및 방법
• 결과
• 고찰
• 참고문헌
• 국문초록

참고문헌 (Reference)

1 Lee HH, "Treadmill exercise decreases intrastriatal hemorrhage-induced neuronal cell death via suppression on caspase-3 expression in rats.Neurosci.Lett" 352 : 33-36, 2003

2 Keller C, "Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content" 15 : 2748-2750, 2001

3 Hallenbeck JM, "The many faces of tumor necrosis factor in stroke" 8 : 1363-1368, 2002

4 Yach D, "The global burden of chronic diseases: overcoming impediments to prevention and control" 291 : 2616-2622, 2004

5 Fallon KE, "The acute phase response and exercise: court and field sports" 35 : 170-173, 2001

6 Mizuhara H, "T cell activation- associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6" 179 : 1529-1537, 1994

7 Hiscock N, "Skeletal myocytes are a source of interleukin-6 mRNA expression and protein release during contraction: evidence of fiber type specificity" 18 : 992-994, 2004

8 Mishima Y, "Relationship between serum tumor necrosis factor-alpha and insulin resistance in obese men with Type 2 diabetes mellitus" 52 : 119-123, 2001

9 Mattusch F, "Reduction of the plasma concentration of C-reactive protein following nine months of endurance training" 21 : 21-24, 2000

10 Pedersen BK, "Possible beneficial role of exercise in modulating low-grade inflammation in the elderly" 13 : 56-62, 2003

11 Pickup JC, "Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes" 67 : 291-300, 2000

12 Ostrowski K, "Physical activity and plasma interleukin-6 in humans-effect of intensity of exercise" 83 : 512-515, 2000

13 Bruunsgaard H, "Physical activity and modulation of systemic low-level inflammation" 78 : 819-835, 2005

14 Febbraio MA, "Muscle-derived interleukin-6: mechanisms for activation and possible biological roles" 16 : 1335-1347, 2002

15 Nybo L, "Interleukin-6 release from the human brain during prolonged exercise" 542 : 991-995, 2002

16 Dandona P, "Inflammation: the link between insulin resistance, obesity and diabetes" 25 : 4-7, 2004

17 Libby P, "Inflammation and atherosclerosis" 105 : 1135-1143, 2002

18 Akiyama H, "Inflammation and Alzheimer's disease" 21 : 383-421, 2000

19 Steensberg A, "IL-6 and TNF-α expression in, and release from, contracting human skeletal muscle" 283 : 1272-1278, 2002

20 Febbraio MA, "Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans" 549 : 607-612, 2003

21 Starkie R, "Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans" 17 : 884-886, 2003

22 Krzyszton CP, "Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation" 295 : 1109-1114, 2008

23 Kakucska I, "Endotoxin-induced corticotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus is mediated centrally by interleukin-1" 133 : 815-821, 1993

24 Watkins LR, "Cytokine-to-brain communication: a review & analysis of alternative mechanisms" 57 : 1011-1026, 1995

25 Woodroofe MN, "Cytokine production in the central nervous system" 45 : 6-10, 1995

26 Schindler R, "Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF" 75 : 40-47, 1990

27 Ostrowski K, "Chemokines are elevated in plasma after strenuous exercise in humans" 84 : 244-245, 2001

28 Ross R, "Atherosclerosis an inflammatory disease" 340 : 115-126, 1999

29 Gan WQ, "Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis" 59 : 574-580, 2004

30 Matthys P, "Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice" 63 : 1158-1164, 1995