首页|茶多酚通过线粒体质量控制改善衰老2型糖尿病模型大鼠肌肉衰减

茶多酚通过线粒体质量控制改善衰老2型糖尿病模型大鼠肌肉衰减

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目的 探讨茶多酚通过线粒体质量控制改善衰老2型糖尿病(type 2 diabetes,T2DM)模型大鼠腓肠肌肌肉衰减的机制。方法 55只8周龄SD雄性大鼠按照体重分为对照组(n=10)、衰老组(n=10)和衰老T2DM组(n=35)。对照组给予普通饲料,每日腹腔注射50 mg/kg生理盐水;衰老组给予普通饲料,每日腹腔注射50 mg/kg D-半乳糖;衰老T2DM组给予高糖高脂饲料,每日腹腔注射50 mg/kgD-半乳糖。4周后,衰老T2DM组一次性腹腔注射30 mg/kg链脲佐菌素,其余2组注射等量柠檬酸缓冲液。注射链脲佐菌素2周后,大鼠空腹血糖≥16。7 mmol/L即判定T2DM模型诱导成功。将其中造模成功的30只大鼠按照空腹血糖值随机分为模型组、300 mg/kg茶多酚组及3 mg/kg罗格列酮组,每组10只。各组继续50 mg/kg D-半乳糖诱导衰老并持续高糖高脂饲料饲养8周,期间相应灌胃干预。实验结束后,Western blot法检测模型组腓肠肌组织P53蛋白的表达,明显高于对照组即判定衰老T2DM大鼠造模成功。检测空腹血糖,计算腓肠肌相对湿重,透射电镜观察腓肠肌线粒体微观结构,及Western Blot检测大鼠腓肠肌线粒体生物合成相关蛋白PGC-1α、线粒体动力学相关蛋白(OPA1、DRP1)、线粒体自噬相关蛋白(P62、LC3)的表达。结果 与对照组相比,衰老T2DM组大鼠空腹血糖升高、腓肠肌P53表达水平上调(P<0。01),即衰老T2DM造模成功。腓肠肌相对湿重降低(P<0。01);腓肠肌组织PGC-1α、OPA1 蛋白表达水平下调(P<0。01),LC3 Ⅱ/LC3 I 降低(P<0。01),DRP1、P62蛋白表达水平上调(P<0。01);线粒体数目明显减少,损伤线粒体数目增多,体积缩小并伴有大量空泡样变,未见明显的自噬溶酶体及分裂融合。干预8周后,与衰老T2DM组相比,茶多酚组大鼠腓肠肌线粒体数目、空泡样变以及分裂融合现象均得到改善,且可见明显增多的自噬溶酶体结构;空腹血糖明显降低(P<0。05),腓肠肌P53表达水平下调(P<0。01);腓肠肌相对湿重增加(P<0。01),PGC-1α(P<0。05)和OPA1 表达量上调(P<0。01),LC3 Ⅱ/LC3 I 增高(P<0。01),DRP1、P62 表达水平下调(P<0。05)。结论 茶多酚可以改善衰老T2DM大鼠合并肌肉衰减的症状,其机制与调控线粒体质量控制有关。
Mechanism of tea polyphenols improving the sarcopenia in the aged type 2 diabetes model rats via mitochondrial quality control
OBJECTIVE To explore whether tea polyphenols(TP)improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC).METHODS A total of 55 2-month-old male SD rats were randomly divided into the control group(n=10),the aged model group(aged,n=10)and the aging T2DM model group(n=35).The aging T2DM model group rats were fed with high-sugar and high-fat diet and intraperitoneally injected with 50 mg/kg D-galactose daily.After 4 weeks,the aging T2DM model group rats were given a single intraperitoneal injection of 30 mg/kg streptozotocin(STZ).After STZ injection for 2 weeks,fasting blood glucose(FBG)≥ 16.7 mmol/L was defined as successful T2DM model.When the model was successfully induced,the 30 model rats were randomly divided into aged T2DM group(Mod),300 mg/kg TP teatment group(TP)and 3 mg/kg rosiglitazone treatment group(RSG)according to FBG,with 10 rats in each group.Each group was treated with 50 mg/kg D-galactose to induce senescence and fed with high glucose and fat for 8 weeks.Western blot was used to detect the expression of P53 protein in gastnemius muscle tissue of the model group at the end of the experiment,which was higher than that of the control group,indicating that the aging T2DM model was successfully established.FBG was detected by the blood glucose meter,gastnemius muscle relative weights was calculated,the microstructure of mitochondria of gastnemius muscle was observed by transmission electron microscope(TEM),the expression of mitochondrial biosynthesis-related proteins PGC-1α,mitochondrial dynamics-related proteins(OPA1,DRP1)and mitochondrial autophagy-related proteins(P62,LC3)in gastnemius muscle were detected by western blot.RESULTS Compared with the control group,the level of FBG and the expression of P53 in the Mod group were increased(P<0.01).The gastnemius muscle relative weights,the expression level of PGC-1α,OPA1 and the ratio of LC3Ⅱ/LC3I were decreased(P<0.01).The expression level of P62 and DRP1 were significantly increased(P<0.01).The number of mitochondria decreased,the volume decreased and a large number of vacuolization,and there were no obvious autophagolysosomes and fission and fusion.After 8 weeks,compared with the Mod group,the number of mitochondria in the gastrocnemius of TP and RSG groups,vacuolization,fission and fusion were improved,and the autophagolysosomes was significantly increased.The expression levels of P53,DRP1 and P62,the level of FBG in the TP group were significantly decreased(P<0.01,P<0.05).The expression levels of OPA1 and PGC-1α,the ratios of LC3Ⅱ/LC3I and gastnemius muscle relative weights were significantly increased(P<0.05,P<0.01).CONCLUSION TP can improve the sarcopenia in the aged T2DM model rats,and its mechanism is related to the regulation of mitochondrial quality control.

tea polyphenolsaged type 2 diabetessarcopeniamitochondrial quality control

陈爽直、王希、张骋、薛璐珊、冯文娟、谢皓然、成乐、吕晨慧、李学敏、赵海峰

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山西医科大学公共卫生学院,煤炭环境致病与防治教育部重点实验室,太原 030001

山西省疾病预防控制中心,太原 030012

茶多酚 衰老2型糖尿病 肌肉衰减 线粒体质量控制

国家自然科学基金中央引导地方科技发展资金山西省回国留学人员科研资助项目山西省研究生教育创新项目山西省研究生教育创新项目

81973047YDZJSX20231A0562023-1032023KY4002023SJ152

2024

卫生研究
中国疾病预防控制中心

卫生研究

CSTPCD北大核心
影响因子:0.761
ISSN:1000-8020
年,卷(期):2024.53(4)