南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (10): 2482-2493.doi: 10.12122/j.issn.1673-4254.2026.10.17
• • 上一篇
张冠男1(
), 李想2, 米源2, 田丹阳2, 孟晋启3(
)
收稿日期:2026-03-06
出版日期:2026-10-20
发布日期:2026-10-26
通讯作者:
孟晋启
E-mail:13483111223@163.com;MengJinqi@hebmu.edu.cn
作者简介:张冠男,硕士,副研究员,E-mail: 13483111223@163.com
基金资助:
Guannan ZHANG1(
), Xiang LI2, Yuan MI2, Danyang TIAN2, Jinqi MENG3(
)
Received:2026-03-06
Online:2026-10-20
Published:2026-10-26
Contact:
Jinqi MENG
E-mail:13483111223@163.com;MengJinqi@hebmu.edu.cn
Supported by:摘要:
目的 探究有氧运动与无氧力竭运动对糖尿病大鼠多器官糖代谢及相关功能的影响及其潜在机制。 方法 将40只雄性SD大鼠随机分为空白对照组(10只)与糖尿病造模组(30只)。采用高脂高糖饮食联合一次性小剂量链脲佐菌素(STZ)注射建立2型糖尿病大鼠模型。造模成功后,随机分为糖尿病对照组(10只)、糖尿病有氧运动组(10只)和糖尿病无氧力竭运动组(10只),并进行8周运动干预。干预结束后,对大鼠一般情况进行测试分析;取肝脏、股四头肌、心脏、脑组织前额叶皮质进行HE染色、Masson染色、PAS染色及免疫组化分析;采用Western blotting和qPCR技术检测肝脏关键代谢酶及基因表达水平。 结果 与空白对照组相比,糖尿病对照组大鼠体质量、肝脏指数、空腹血糖及血清乳酸、丙酮酸、尿素氮、肌酐、肌酸激酶水平均显著升高(P<0.01);肝脏出现脂肪变性,显著纤维化及糖原减少(P<0.01);骨骼肌出现结构损伤,显著纤维化及糖原减少(P<0.01);心肌结构损伤、炎症浸润;前额叶皮质多巴胺受体DRD1/DRD5、5-HT、TH表达显著下降(P<0.01)。与糖尿病对照组相比,糖尿病有氧组大鼠体质量、肝脏指数、空腹血糖及血清乳酸、丙酮酸、肌酐、尿素氮、肌酸激酶均显著降低(P<0.01);肝脏纤维化减轻(P<0.01),糖原沉积增加(P<0.01),糖异生关键酶G6PC及糖酵解酶表达下调(P<0.01),Sirt1 mRNA表达上调(P<0.01);骨骼肌糖原含量增加(P<0.01);心肌结构改善,炎症减轻;前额叶皮质DRD1、DRD5、5-HT、TH表达显著回升(P<0.01)。与糖尿病对照组相比,糖尿病力竭组体质量、空腹血糖下降(P<0.01),但肝脏指数、血清乳酸、丙酮酸、尿素氮、肌酐及肌酸激酶水平进一步升高(P<0.05或P<0.01);肝脏纤维化加剧(P<0.01),糖原沉积减少(P<0.01),糖酵解酶表达上调(P<0.01);骨骼肌纤维化加剧(P<0.01);心肌损伤加重;前额叶皮质DRD1、TH表达进一步降低(P<0.05)。 结论 有氧运动通过调节糖脂代谢、减轻炎症纤维化及改善神经递质功能,全面保护糖尿病大鼠多器官功能;而无氧力竭运动加剧了代谢紊乱与组织损伤。
张冠男, 李想, 米源, 田丹阳, 孟晋启. 有氧运动通过调控Sirt1/Creb1/Ppargc1a表达改善糖尿病大鼠代谢紊乱及多器官损伤[J]. 南方医科大学学报, 2026, 46(10): 2482-2493.
Guannan ZHANG, Xiang LI, Yuan MI, Danyang TIAN, Jinqi MENG. Aerobic exercise improves metabolic disorders and multi-organ damage in diabetic rats by activating the Sirt1/Creb1/Ppargc1a axis[J]. Journal of Southern Medical University, 2026, 46(10): 2482-2493.
| Primer | Sequence |
|---|---|
| Rat-Btubulin-F1 | TAGCAGCGTTGCTGGGTATC |
| Rat-Btubulin-R1 | GACTGGAATGCCTCGCTCTT |
| Rat-Sirt1-F1 | TCAGAACCACCAAAGCGGAA |
| Rat-Sirt1-R1 | GCAAGGCGAGCATAAATACCA |
| Rat-Creb1-F1 | TCCTCCCCAGCACTTCCTAC |
| Rat-Creb1-R1 | CCAATCCAGTCCATTTTCCA |
| Rat-Ppargc1a-F2 | AACAGAAACAGCAGCAGAGACAA |
| Rat-Ppargc1a-R2 | GCAGTTCCAGAGAGTTCCACAC |
表1 目的基因引物序列
Tab.1 Primer sequences for qPCR of the target genes
| Primer | Sequence |
|---|---|
| Rat-Btubulin-F1 | TAGCAGCGTTGCTGGGTATC |
| Rat-Btubulin-R1 | GACTGGAATGCCTCGCTCTT |
| Rat-Sirt1-F1 | TCAGAACCACCAAAGCGGAA |
| Rat-Sirt1-R1 | GCAAGGCGAGCATAAATACCA |
| Rat-Creb1-F1 | TCCTCCCCAGCACTTCCTAC |
| Rat-Creb1-R1 | CCAATCCAGTCCATTTTCCA |
| Rat-Ppargc1a-F2 | AACAGAAACAGCAGCAGAGACAA |
| Rat-Ppargc1a-R2 | GCAGTTCCAGAGAGTTCCACAC |
| Variables | Blank control group | Diabetes control group | Diabetes aerobic group | Diabetes exhaustion group |
|---|---|---|---|---|
| Weight (g) | 328.90±10.73 | 379.50±11.88** | 350.10±12.68## | 296.60±14.16## |
| Liver wet weight (g) | 14.22±1.52 | 26.49±2.64** | 19.26±2.49## | 29.60±3.12# |
| Liver index (%) | 4.33±0.51 | 6.99±0.75** | 5.50±0.64## | 9.97±0.78## |
表2 各组大鼠体质量、肝脏湿质量、肝脏指数变化
Tab.2 Changes in body weight, liver wet weight, and liver index of the rats in each group (Mean±SD, n=10)
| Variables | Blank control group | Diabetes control group | Diabetes aerobic group | Diabetes exhaustion group |
|---|---|---|---|---|
| Weight (g) | 328.90±10.73 | 379.50±11.88** | 350.10±12.68## | 296.60±14.16## |
| Liver wet weight (g) | 14.22±1.52 | 26.49±2.64** | 19.26±2.49## | 29.60±3.12# |
| Liver index (%) | 4.33±0.51 | 6.99±0.75** | 5.50±0.64## | 9.97±0.78## |
| Variables | Blank control group | Diabetes control group | Diabetes aerobic group | Diabetes exhaustion group |
|---|---|---|---|---|
| FBG (mmol/L) | 6.24±0.72 | 13.09±1.06** | 8.11±0.85## | 10.29±0.72## |
| Lactic acid (mmol/L) | 2.55±0.39 | 3.97±0.50** | 3.05±0.46## | 6.46±0.65## |
| Pyruvic acid (mmol/L) | 0.42±0.05 | 0.82±0.11** | 0.61±0.10## | 1.11±0.17## |
| Creatinine (mg/dL) | 0.61±0.08 | 1.55±0.16** | 0.82±0.13## | 2.35±0.27## |
| Urea nitrogen (mmol/L) | 3.70±0.28 | 6.19±0.98** | 4.73±0.65## | 7.46±0.97# |
| Creatine kinase (U/L) | 115.70±24.00 | 305.30±30.42** | 191.30±24.41## | 508.90±58.60## |
表3 各组大鼠空腹血糖、血乳酸、丙酮酸、肌酐、尿素氮、肌酸激酶水平变化
Tab. 3 Changes in fasting blood glucose, blood lactate, pyruvate, creatinine, blood urea nitrogen, and creatine kinase levels in each group of the rats (Mean±SD, n=10)
| Variables | Blank control group | Diabetes control group | Diabetes aerobic group | Diabetes exhaustion group |
|---|---|---|---|---|
| FBG (mmol/L) | 6.24±0.72 | 13.09±1.06** | 8.11±0.85## | 10.29±0.72## |
| Lactic acid (mmol/L) | 2.55±0.39 | 3.97±0.50** | 3.05±0.46## | 6.46±0.65## |
| Pyruvic acid (mmol/L) | 0.42±0.05 | 0.82±0.11** | 0.61±0.10## | 1.11±0.17## |
| Creatinine (mg/dL) | 0.61±0.08 | 1.55±0.16** | 0.82±0.13## | 2.35±0.27## |
| Urea nitrogen (mmol/L) | 3.70±0.28 | 6.19±0.98** | 4.73±0.65## | 7.46±0.97# |
| Creatine kinase (U/L) | 115.70±24.00 | 305.30±30.42** | 191.30±24.41## | 508.90±58.60## |
图1 各组大鼠骨骼肌组织HE染色、Masson染色、PAS染色
Fig.1 Histopathological changes in skeletal muscles of the rats in each group. A: HE staining, Masson staining, and PAS staining of mouse skeletal muscle tissues (Scale bar=100 μm). B: Collagen volume fraction of the rats in each group. C: Percentage of PAS-positive area in each group of rats. Data are presented as Mean±SD (n=10). a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group. Arrows indicate damaged muscle fibers, inflammatory cell infiltration, and vacuolar degeneration. **P<0.01 vs blank control group; ##P<0.01 vs the diabetes control group.
图2 各组大鼠心肌组织HE染色
Fig.2 HE staining of myocardial tissue from rats in each group (Scale bar=100 μm). a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group. Arrows indicate disordered and ruptured myocardial fibers, widened intercellular spaces, and necrotic areas.
图3 各组大鼠前额叶皮质DRD1、DRD5、5-HT、TH的表达分布
Fig.3 Expression distribution of DRD1, DRD5, 5-HT, and TH in the prefrontal cortex of rats in each group (Scale bar=100 μm. a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group.
图4 各组大鼠前额叶皮质DRD1、DRD5、5-HT、TH的平均光密度
Fig.4 Average optical density of DRD1 (A), DRD5 (B), 5-HT (C) and TH (D) in the prefrontal cortex of the rats in each group (Mean±SD, n=10). **P<0.01 vs the blank control group; #P<0.05, ##P<0.01 vs the diabetes control group. a. Blank control group; b. Diabetes control group; c. Diabetes aerobic group; d. Diabetes exhaustive group.
图5 各组大鼠肝脏组织G6PC、PFK、GAPDH、PKM1蛋白表达
Fig.5 Protein expressions of G6PC, PFK, GAPDH and PKM1 in liver tissues of the rats in each group. A: Protein expression levels of G6PC and PFK detected by Western blotting. B: Protein expression levels of GAPDH and PKM1 detected by Western blotting. C: Expression levels of G6PC and PFK in the liver tissues of different groups. D: Expression levels of GAPDH and PKM1 in liver tissues of different groups. Data are presented as Mean±SD (n=10). *P<0.05, **P<0.01 vs the blank control group; ##P<0.01 vs the diabetes control group. a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group.
图6 各组大鼠肝脏组织LDH、 SDHA、PCB蛋白表达
Fig.6 Protein expression of LDH, SDHA and PCB in liver tissues of rats in each group. A: Detection of protein expression levels of LDH and SDHA by Western blotting. B: Detection of protein expression levels of PCB by Western blotting. C: Expression levels of SDHA, LDH and PCB in liver tissues of different groups (Mean±SD, n=10).*P<0.05, **P<0.01 vs blank control group; ##P<0.01 vs the diabetes control group. a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group.
图7 各组大鼠肝脏组织HE染色、Masson染色、PAS染色
Fig.7 HE, Masson, and PAS staining (A) of liver tissues, collagen volume fraction (B) and percentage of PAS-positive area in each group (Scale bar=100 μm). Data are presented as Mean±SD (n=10). a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group. Arrows indicate lipid vacuoles of varying sizes and inflammatory cell infiltration in hepatocytes. **P<0.01 vs blank control group; ##P<0.01 vs the diabetes control group.
图8 各组大鼠肝脏Sirt1、Creb1、Ppargc1a的基因表达水平变化
Fig.8 Changes in mRNA expression of Sirt1, Creb1, and Ppargc1a in the livers of rats in each group (Mean±SD, n=10).*P<0.05, **P<0.01 vs the blank control group; ##P<0.01 vs the diabetes control group. a: Blank control group; b: Diabetes control group; c: Diabetes aerobic group; d: Diabetes exhaustive group.
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