有氧运动对糖尿病大鼠PPARα信号通路的影响及其与PPARγ关系*

doi:10.12047/j.cjap.5945.2020.067

摘要/Abstract

摘要： 目的: 探讨4周有氧运动对糖尿病大鼠血糖血脂的改善作用及其与PPARα和PPARγ的调控关系。方法: 6周龄雄性SD大鼠8周高脂饮食喂养后一次性腹腔注射链脲佐菌素以建立糖尿病模型大鼠。除普通膳食对照组(Con)外,建模成功的糖尿病大鼠随机分成糖尿病对照组(DM)、糖尿病运动组(TDM)、糖尿病运动加PPARγ激动剂吡格列酮组(TDP)和糖尿病运动加PPARγ抑制剂GW9662组(TDG),每组8只。TDP组和TDG组大鼠在运动前分别补充吡格列酮和GW9662,TDM、TDP和TDG组大鼠进行4周中等强度递增负荷跑台运动(第1周15 m/min,30 min;第2周15 m/min,60 min;第3周20 m/min,60 min;第4周20 m/min,90 min),每周运动6 d,每天1次。运动期间所有大鼠给予普通饲料。最后一次运动结束后36 h,大鼠麻醉、取血,然后处死大鼠、收集肝和腓肠肌。检测空腹血糖血脂指标(血糖、血胰岛素和血脂四项)。Western blot方法检测肝和腓肠肌PPARα、PPARα上游分子腺苷酸活化蛋白激酶(AMPK)和下游分子肉碱棕榈酰转移酶-1(CPT1)的蛋白水平。结果: ①与Con组大鼠比较,DM大鼠FBG(＞11.1 mmol/L)和血清TC、TG、LDL水平显著升高(P均＜0.01),表明DM造模成功。②与DM大鼠比较,TDM大鼠血糖血脂改善的同时,肝和腓肠肌PPARα、AMPK和CPT1的蛋白水平均显著升高(P均＜0.01)。③与TDM大鼠比较,TDG大鼠肝和腓肠肌的PPARα和CPT1,以及肝AMPK的蛋白水平无显著变化(仅腓肠肌AMPK显著降低(P＜0.05));而TDP大鼠的肝和腓肠肌PPARα、AMPK和CPT1蛋白水平均显著提高(P均＜0.01)。结论: 有氧运动对DM大鼠血糖血脂的改善作用-与运动激活肝和腓肠肌的AMPK-PPARα-CPT1通路有关。运动对DM大鼠PPARα通路的激活与PPARγ无关,但PPARγ激活可进一步增强运动对AMPK-PPARα-CPT1蛋白水平上调的作用。

关键词: 有氧运动, PPARα, PPARγ, AMPK, CPT1, 糖尿病, 大鼠

Abstract: Objective: To investigate the improved effects of 4-week aerobic exercise on blood glucose and lipid of diabetes mellitus (DM) rats and its association with peroxisome proliferators-activated receptor (PPAR)α signaling and PPARγ. Methods: Six-week old male SD rats were fed with 8-week high-fat diet following a single intraperitoneal injection of streptozotocin to establish DM models rats. Except control group rats (fed with ordinary diet), DM model rats were randomly divided into DM group, trained DM group (TDM), TDM plus PPARγ agonist pioglitazone group (TDP), and TDM plus PPARγ inhibitor GW9662 group (TDG), 8 rats in each group. TDM, TDP and TDG rats were undertaken a medium-intensity incremental treadmill training for 4 weeks, once a day and 6 days a week (1^st week: 15 m/min speed lasting for 30 min; 2^nd week: 15 m /min for 60 min; 3^rd week: 20 m/min for 60 min; 4^th week: 20 m/min for 90 min). All the rats were fed with ordinary diet during 4-week exercise. The rats were anesthetized and blood samples were collected at 36 h after the last exercise, and liver and gastrocnemius were collected after the rats were sacrificed. Fasting blood glucose and blood lipid were detected (blood glucose, insulin and TC, TG, HDL and LDL). The protein levels of PPARα, adenosine monophosphate (AMP)-activated protein kinase (AMPK) and carnitine palmitoyl transferase 1 (CPT1) in the liver and gastrocnemius of the rats were measured by Western blot. Results: ①Compared with control rats, the serum levels of TC, TG, LDL, and FBG (＞11.1 mmol/L) in DM rats were significantly increased, indicated the successful establishment of DM rats. ②Compared with DM rats, accompanied with the improvements of fasting blood glucose and blood lipid, the protein levels of PPARα, AMPK and CPT1 were significantly increased in the liver and gastrocnemius of TDM rats. ③Compared with TDM rats, no significant changes were found in TDG rats including the protein levels of PPARα and CPT1 (liver and gastrocnemius) as well as AMPK (liver), except for a decrease of AMPK in gastrocnemius; while the protein levels of PPARα, AMPK and CPT1 were all increased in the liver and gastrocnemius of TDP rats. Conclusion: Aerobic exercise-induced improvements of blood glucose and blood lipid was related to the up-regulation of AMPK-PPARα-CPT1 signaling pathway in the liver and muscle of DM rats. The exercise-induced enhancement of PPARα in DM rats was unrelated to PPARγ, but PPARγ activation could further increase the protein levels of AMPK-PPARα-CPT1 in TDM rats.

Key words: aerobic exercise, PPARα, PPARγ, AMPK, CPT1, diabetes, rat

中图分类号:

G804.2

王天源, 王晓慧. 有氧运动对糖尿病大鼠PPARα信号通路的影响及其与PPARγ关系^*[J]. 中国应用生理学杂志, 2020, 36(4): 312-317.

WANG Tian-yuan, WANG Xiao-hui. Effects of aerobic exercise on PPARα signaling in diabetes rats and its association with PPARγ[J]. CJAP, 2020, 36(4): 312-317.

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有氧运动对糖尿病大鼠PPARα信号通路的影响及其与PPARγ关系^*

Effects of aerobic exercise on PPARα signaling in diabetes rats and its association with PPARγ

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