活性氧诱导运动中肌源性IL-6产生的信号转导通路述评

就运动中活性氧诱导肌原性IL-6产生的机制等问题做综述。IL-6是运动过程中变化非常明显的一种细胞因子,其变化幅度与运动时间和运动强度关系密切。研究表明,运动中生成的IL-6主要来源于收缩的骨骼肌,骨骼肌在运动过程中产生的自由基,尤其是活性氧是运动中诱导IL-6产生的一个主要原因。     

运动应激所致血清IL-1β和IL-6浓度增加及其作用研究

目的：探索运动应激时血清白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）浓度变化及其与糖代谢和细胞免疫的关系。方法：非体育专业男大学生，空腹，以200W蹬车2min，间歇5min，重复运动至极度疲劳。检测运动前、运动后即刻和运动后3h血清IL-1β、IL-6、皮质醇（Cor）、血糖（GLU）和血乳酸（BLA）浓度以及T-淋巴细胞转换指数（T-LTI）变化。结果：在运动后即刻，血清GLU、BLA、IL-1β、IL-6和Cor浓度增加幅度分别达运动前的40％、314％、75％、110％和95％（P〈0．001），而T-LTI则下降了31％（P〈0．001），经3h休息，Cor、GLU和T-LTI未完全恢复，但BLA、IL-1β和IL-6基本恢复；IL-1β、IL-6、Cor分别与GLU和BLA呈正相关（P〈0．05），但与T-LTI均呈负相关（P〈0．05）；Cor分别与IL-1β和IL-6呈正相关（P〈0．05）。结论：IL-1β和IL-6在运动应激期间主要参与糖代谢的调节，对细胞免疫功能有一定抑制作用。     

运动与细胞因子的研究进展

运动期间血浆细胞因子主要来源于收缩的骨骼肌和脂肪组织，尤其是IL-6。运动时糖和脂肪的代谢与IL-6有关，IL-6也可能参与肌纤维溶解和肌肉萎缩。IL-15可能介导力量训练所致的肌肉壮大。免疫细胞不是运动中血浆细胞因子的主要来源。     

运动诱导肌源性 IL26 基因表达和蛋白释放与 G L UT4 基因表达的关系研究

目的:研究不同肌糖原状态下运动诱导肌源性白细胞介素6(Interukin-6,IL-6)表达及蛋白释放与葡萄糖转运体4(Glucose Transport 4,GLUT4)基因表达的关系.方法:通过特定的运动方案和饮食方案造成大鼠在运动前体内肌糖原含量不同,再观察定量负荷跑台运动后肌源性IL-6表达及释放与葡萄糖转运体GLUT4基因表达的变化规律.结果:血清IL-6浓度在运动30min后显著增加,运动120min后达到峰值,运动后逐渐降低;骨骼肌IL-6mRNA在运动120min后显著增加,运动后3-6h继续增加至峰值;骨骼肌GLUT4mRNA在运动时并未增加,而在运动后3h开始增加,运动后6h达到峰值.上述三个指标在低肌糖原组的增加与正常糖原组相比更加显著.结论:低肌糖原含量可以促进运动中IL-6的释放及运动后恢复期IL-6和GLUT4的基因表达;运动导致恢复期GLUT4基因表达的增加很有可能与肌源性IL-6的表达及IL-6的自分泌作用有关.     

运动与白细胞介素-6

采用文献资料分析法，总结了白细胞介素-6(IL-6)的最新研究成果。结果表明，运动能够诱导局部工作的肌肉产生IL-6，并可能参与调节和运动有关的代谢变化。     

运动诱导骨骼肌分泌白细胞介素-6的研究进展

早期研究理论认为，骨骼肌是人体主要的运动器官，最近有资料研究表明，骨骼肌也是人体最大的内分泌器官，能表达、合成和分泌多种生物信号分子，细胞因子IL-6是其中之一。运动诱导的IL-6介导了免疫调节和抗炎性效应。本文仅对骨骼肌分泌的IL-6产生的可能机制及在运动人体科学中的生物学意义以及骨骼肌“新”的功能进行综述。     

运动训练对热应激大鼠免疫机能的影响

为了探讨运动和热应激对大鼠白介素2（IL-2）等免疫指标的影响，对大鼠进行为期6周的中等强度负荷运动训练，并在运动末次施加热应激，测定大鼠外周血液白介素2（IL-2）含量、胸腺指数、脾脏指数。结果：（1）运动热应激组大鼠血清中IL-2含量、胸腺指数、脾脏指数显著低于对照组；（2）运动热应激组与热应激组相比，运动热应激组大鼠血清中IL-2含量、胸腺指数、脾脏指数则显著低于对照组；（3）运动热应激与常温急性运动组相比。运动热应激组的大鼠血清中IL-2含量、胸腺指数、脾脏指数显著低于对照组。结论：（1）长时间运动热应激时机体免疫机能受到损伤程度明显增加；（2）在常温下进行中等强度的运动训练，可以适当提高机体的耐热性，降低免疫抑制和损伤。     

低肌糖原含量刺激运动引起的大鼠骨骼肌IL-6基因转录的机制研究

目的:验证骨骼肌白细胞介素6(interleukin6,IL-6)基因转录的增加可能与c-Jun氨基末端激酶(c-Jun NH2-terminal kinases,JNK)信号通道的激活有关,并且探讨运动前肌糖原含量是否影响收缩骨骼肌JNK信号通道的激活。方法:大鼠先进行糖原消耗运动,在恢复期24h内采取不同的膳食干预手段,使大鼠在下一次定量运动前骨骼肌肌糖原含量不同。结果:运动时,血浆IL-6浓度、骨骼肌IL-6mRNA及核磷酸化JNK含量均显著上升,运动后恢复期降低;在相同时间点,低糖原组血浆IL-6浓度及骨骼肌IL-6 mRNA均显著高于正常糖原组;在相同时间点,核磷酸化JNK含量在低糖原组与高糖原组之间没有显著性差异。结论:收缩骨骼肌中,IL-6基因转录可能与低糖原含量及JNK信号通道的激活有关,然而,低糖原促进的IL-6基因转录可能不是通过激活JNK信号通道。     

大蒜素与联合抗氧化剂干预对运动员DOMS和血浆IL-6水平变化的影响

目的:探讨大蒜素与联合抗氧化剂干预对运动员大强度离心运动后不同时相肌肉酸痛程度、血浆白细胞介素6(IL-6)水平变化的影响.方法:运动员 24 名,随机均衡分为对照组(A组)、联合抗氧化剂组(B组)和大蒜素组(C组),运动前2周至运动后2天每天分别口服安慰剂、联合抗氧化剂或大蒜素肠溶胶丸.服药两周后进行一次大强度离心跑台运动,建立运动员运动延迟性肌肉酸痛(DOMS)模型,在服药前、运动前和运动后即刻、24 h、48 h分别测定运动员肘正中静脉血IL-6浓度及运动后相应时相肌肉酸痛程度.结果:3组运动员运动后肌肉酸痛程度均呈延迟性,B、C组运动员运动后各时相肌肉酸痛程度与血浆IL-6浓度均低于A组同时相.C组运动员肌肉酸痛程度运动后各时相均高于B组同时相,而血浆IL-6的浓度运动后各时相均低于B组同时相,但均无显著性差异.结论:联合抗氧化剂与大蒜素均可减轻运动员离心运动导致的DOMS,抑制IL-6的产生;大蒜素可能通过降低运动应激,减小肌纤维损伤与炎症反应等作用,抑制运动后血浆IL-6浓度的升高;联合抗氧化剂可通过几种抗氧化成分的协同作用,减轻大强度离心运动导致的DOMS.     

运动对肌糖原贮备不同大鼠脂肪细胞白细胞介素-6及受体和激素敏感性脂肪酶基因表达的影响

研究目的观察定量运动对肌糖原贮储不同大鼠脂肪细胞白细胞介素-6及受体和激素敏感性脂肪酶基因表达的变化.研究方法通过跑台运动与膳食干预来造成运动前大鼠肌糖原储备不同,分为正常(肌)糖原组和低(肌)糖原组,然后再进行定量跑台运动.在运动过程中宰杀进行动态观察.通过实时荧光定量PCR法测定脂肪细胞中的白细胞介素-6及受体和激素敏感性脂肪酶的mRNA.结果研究发现,定量运动引起了脂肪组织中IL-6mRNA、IL-6RmRNA和HSLmRNA上升,其中IL-6mRNA和HSLmRNA的上升并不存在肌糖原储备的差异,而IL-6RmRNA则不然.结论定量运动过程中肌糖原储备的差异对脂肪组织IL-6RmRNA的影响深刻,而对IL-6mRNA和HSLmRNA的影响较小.     

Individual differences in the interleukin-6 response to maximal and submaximal exercise tasks

The inflammatory responsive cytokine interleukin-6 (IL-6) helps regulate immune responses to exercise. Evidence suggests that increases in IL-6 are related to exercise duration and intensity. However, the moderating effect of sex and underlying mediators have received limited attention. We compared plasma IL-6 responses to two cycling tasks with a resting control in young male (n = 12) and female (n = 12) recreationally active adults. Both 45 min tasks comprised an incremental test, either maximal or submaximal, followed by steady-state exercise at 55% peak power output. Interleukin-6 was elevated above baseline immediately after the maximal but not the submaximal task. Compared with the control condition, IL-6 was increased at 30 and 60 min after both exercise tasks. The IL-6 response was greater in women than men at 60 min after maximal exercise. Cortisol increased in both tasks compared with the control condition, the increase being greater after maximal than submaximal exercise. No associations were found between IL-6 responses and cortisol, heart rate, fitness or body mass index. The results show that 45 min of moderate-intensity exercise can increase IL-6 and suggest that the inclusion of maximal effort may accelerate this response. The finding that women showed a greater IL-6 response to maximal exercise may reflect a gender dimorphism in the immune response to stress.     

Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise

Abstract

Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline + 48 h); and eccentric exercise plus Cr 48 h (Cr + 48h). Cr supplementation was administered as a solution of 300 mg · kg body weight^?1 · day^?1 in 1 mL water, for two weeks, before the eccentric exercise. The animals were submitted to one downhill run session at 1.0 km · h^?1 until exhaustion. Twenty-four and forty-eight hours after the exercise, the animals were killed, and the quadriceps were removed. Creatine kinase levels, superoxide production, thiobarbituric acid reactive substances (TBARS) level, carbonyl content, total thiol content, superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL-1β), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were analysed. Cr supplementation neither decreases Cr kinase, superoxide production, lipoperoxidation, carbonylation, total thiol, IL-1β, NF-kb, or TNF nor alters the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides in relation to the saline group, respectively (P < 0.05). There are positive correlations between Cr kinase and TBARS and TNF-α 48 hours after eccentric exercise. The present study suggests that Cr supplementation does not decrease oxidative stress and inflammation after eccentric contraction.     

Vitamin C supplementation does not influence plasma and blood mononuclear cell IL-6 and IL-10 levels after exercise

Abstract

The aim of this study was to determine whether the highest vitamin C supplementation associated with complete bioavailability influences the plasma and blood mononuclear cell IL-6 and IL-10 response to exercise. A double-blinded study of supplementation with vitamin C was performed. After 15 days of supplementation with vitamin C (500 mg · day^?1, n = 16) or a placebo (n = 15), participants in the study completed a 15-km run competition. Blood samples were taken before and after competition. Oxidative stress markers, antioxidants, cortisol, IL-6 and IL-10 were determined in plasma or serum. IL-6 and IL-10 protein and mRNA levels were measured in blood mononuclear cells. Although higher plasma and blood mononuclear cell vitamin C levels were observed in the supplemented group when compared with the placebo one, the two groups showed identical exercise-induced changes in all the measured parameters. Exercise induced increased IL-6 and IL-10 levels in plasma and blood mononuclear cells. IL-6 and IL-10 mRNA levels in blood mononuclear cells increased after the competition. After recovery, IL-6 mRNA returned to basal levels and IL-10 mRNA levels remained elevated. In conclusion, exercise induced increased IL-6 and IL-10 production in blood mononuclear cells. However, vitamin C supplementation did not influence IL-6 and IL-10 response to exercise.     

Individual differences in the interleukin-6 response to maximal and submaximal exercise tasks

Abstract

The inflammatory responsive cytokine interleukin-6 (IL-6) helps regulate immune responses to exercise. Evidence suggests that increases in IL-6 are related to exercise duration and intensity. However, the moderating effect of sex and underlying mediators have received limited attention. We compared plasma IL-6 responses to two cycling tasks with a resting control in young male (n = 12) and female (n = 12) recreationally active adults. Both 45 min tasks comprised an incremental test, either maximal or submaximal, followed by steady-state exercise at 55% peak power output. Interleukin-6 was elevated above baseline immediately after the maximal but not the submaximal task. Compared with the control condition, IL-6 was increased at 30 and 60 min after both exercise tasks. The IL-6 response was greater in women than men at 60 min after maximal exercise. Cortisol increased in both tasks compared with the control condition, the increase being greater after maximal than submaximal exercise. No associations were found between IL-6 responses and cortisol, heart rate, fitness or body mass index. The results show that 45 min of moderate-intensity exercise can increase IL-6 and suggest that the inclusion of maximal effort may accelerate this response. The finding that women showed a greater IL-6 response to maximal exercise may reflect a gender dimorphism in the immune response to stress.     

The response of plasma interleukin-6 and its soluble receptors to exercise in the cold in humans

In this study, we wished to determine whether the changes in metabolism observed during exercise in the cold are associated with changes in interleukin-6 (IL-6) and/or its soluble receptors. Eight healthy male participants performed 1 h of cycling exercise at 70% VO2max in a control (20 degrees C) and cold (0 degrees C) environment. Plasma concentrations of IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured before exercise, at 30 and 60 min of exercise, and 60 min after exercise. Substrate oxidation was estimated through measures of pulmonary gas exchange recorded between 50 and 55 min of cycling. Exercise in the cold resulted in an increase (P < 0.05) in carbohydrate oxidation (mean 2.58 g.min(-1), s = 0.49 at 20 degrees C vs. 2.85 g.min(-1), s = 0.58 at 0 degrees C) and a decrease (P < 0.05) in fat oxidation (0.55 g.min(-1), s = 0.17 at 20 degrees C vs. 0.38 g.min(-1), s = 0.16 at 0 degrees C) compared with the control trial. Interleukin-6 concentrations were elevated (P < 0.05) after 60 min of exercise in both the cold and control trials, with no differences between trials at any instant. Neither sIL-6R nor sgp130 was affected by exercise or the environment. The alterations in carbohydrate and fat utilization during 1 h of exercise in the cold are not paralleled by changes in plasma concentrations of IL-6 or its soluble receptors.     

Changes in cytokines,leptin, and IGF-1 levels in overtrained athletes during a prolonged recovery phase: A case-control study

We investigated how cytokines are implicated with overtraining syndrome (OTS) in athletes during a prolonged period of recovery. Plasma IL-6, IL-10, TNF-α, IL-1β, adipokine leptin, and insulin like growth factor-1 (IGF-1) concentrations were measured in overtrained (OA: 5 men, 2 women) and healthy control athletes (CA: 5 men, 5 women) before and after exercise to volitional exhaustion. Measurements were conducted at baseline and after 6 and 12 months. Inflammatory cytokines did not differ between groups at rest. However, resting leptin concentration was lower in OA than CA at every measurement (P < 0.050) but was not affected by acute exercise. Although IL-6 and TNF-α concentrations increased with exercise in both groups (P < 0.050), pro-inflammatory IL-1β concentration increased only in OA (P < 0.050) and anti-inflammatory IL-10 was greater in CA (P < 0.001). In OA, exercise-related IL-6 and TNF-α induction was enhanced during the follow-up (P < 0.050). IGF-1 decreased with exercise in OA (P < 0.050); however, no differences in resting IGF-1 were observed. In conclusion, low leptin level at rest and a pro-inflammatory cytokine response to acute exercise may reflect a chronic maladaptation state in overtrained athletes. In contrast, the accentuation of IL-6 and TNF-α responses to acute exercise seemed to associate with the progression of recovery from overtraining.     

Interleukin-6: Possible biological roles during exercise

Abstract

Interleukin-6 (IL-6) is a multifunctional cytokine that exerts its modulatory effects on cells that express membrane bound IL-6 receptors; however, IL-6 in a complex with soluble IL-6R can bind to any cell that express glycoprotein 130 (gp130). Thus, all cell types may respond to the pro- as well as anti-inflammatory properties of IL-6. Since the first report of acute exercise-induced increase in plasma IL-6 in the early 1990s, scientists have tried to elucidate the factors that influence the magnitude of change of plasma IL-6, as well as the possible biological roles of this cytokine. Evidence suggests that exercise intensity and duration as well as the form of contraction (e.g. eccentric or concentric) and muscle damage all influence IL-6 response to acute exercise. However, data on training status and performance on plasma IL-6 concentration changes during exercise are more inconclusive, as discussed in this review. In the last decade, most of the studies have focused on IL-6 as an ‘energy sensor’ possibly secreted by skeletal muscle that activates glycogenolysis in the liver and lipolysis in fat tissue in order to provide muscle with the growing energy demands during exercise.     

Exercise promotes IL-6 release from legs in older men with minor response to unilateral immobilization

Physical inactivity is a major contributor to low-grade systemic inflammation. Most of the studies characterizing interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) release from exercising legs have been done in young, healthy men, but studies on inactivity in older people are lacking. The impact of 14 days of one-leg immobilization (IM) on IL-6 and TNF-α release during exercise in comparison to the contralateral control (CON) leg was investigated. Fifteen healthy men (age 68.1?±?1.1?year (mean?±?SEM); BMI 27.0?±?0.4 kg·m²; VO₂max 33.3?±?1.6 ml·kg^?1·min^?1) performed 45?min of two-leg dynamic knee extensor exercise at 19.5?±?0.9 W. Arterial and femoral venous blood samples from the CON and the IM legs were collected every 15?min during exercise, and thigh blood flow was measured with ultrasound Doppler. Arterial plasma IL-6 concentration increased with exercise (rest vs. 45?min, main effect p?p?p?=?.085, effect size 0.28) higher in the IM leg compared to the CON leg (288 (95% CI: 213–373) vs. 220 (95% CI: 152–299) pg·min^?1, respectively). There was no release of TNF-α in either leg and arterial concentrations remained unchanged during exercise (p?>?.05). In conclusion, exercise induces more pronounced IL-6 secretion in healthy older men. Two weeks of unilateral immobilization on the other hand had only a minor influence on IL-6 release. Neither immobilization nor exercise had an effect on TNF-α release across the working legs in older men.     

不同运动方式对绝经后女性IL-6、TNF-α和hs-CRP的影响

目的比较12周有氧运动或抗阻训练对绝经后女性白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和高敏C-反应蛋白(hs-CRP)影响的差异,为制定特异性的运动处方提供依据。方法将符合标准的受试者随机分为有氧运动组(18人),抗阻训练组(17人)和对照组(20人)。有氧运动组和抗阻训练组进行每周3次、共12周的运动干预,对照组保持日常生活习惯不变。实验前后分别测定血清IL-6、TNF-α、hs-CRP等指标。结果 12周运动干预后,有氧运动组血清IL-6较运动前下降了13%(P<0.01),血清TNF-α(P>0.05)和hs-CRP(P>0.05)无显著性变化;抗阻训练组血清IL-6较运动前无显著性变化(P>0.05),但血清TNF-α和hs-CRP分别下降了11%(P<0.05)和26%(P<0.05)。对照组所有指标的变化不明显。相关分析显示,实验前hs-CRP基础值与BMI(r=0.36,P<0.01)、空腹血糖(r=0.23,P<0.05)和IL-6(r=0.22,P<0.01)正相关,与VO2max(r=-0.29,P<0.05)负相关;实验后hs-CRP的变化值与BMI的变化值(r=0.21,P<0.05)正相关。结论 绝经妇女慢性全身性炎症状态与其BMI、血糖水平和体内炎症因子的水平有关;12周有氧运动或抗阻训练均能有效改善绝经后女性慢性全身性炎症状态,但抗阻训练的效果优于有氧运动,其原因与BMI的改善有关。