Chen Shuangzhi, Wang Xi, Zhang Cheng, Xue Lushan, Feng Wenjuan, Xie Haoran, Cheng Le, Lyu Chenhui, Li Xuemin, Zhao Haifeng
School of Public Health, Shanxi Medical University, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Taiyuan 030001, China.
Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China.
Wei Sheng Yan Jiu. 2024 Jul;53(4):540-546. doi: 10.19813/j.cnki.weishengyanjiu.2024.04.004.
To explore whether tea polyphenols(TP) improve sarcopenia in the aged type 2 diabetes(T2DM)model rats via mitochondrial quality control(MQC).
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.
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).
TP can improve the sarcopenia in the aged T2DM model rats, and its mechanism is related to the regulation of mitochondrial quality control.
探讨茶多酚（TP）是否通过线粒体质量控制（MQC）改善老年2型糖尿病（T2DM）模型大鼠的肌肉减少症。
将55只2月龄雄性SD大鼠随机分为对照组（n = 10）、老年模型组（老年，n = 10）和老年T2DM模型组（n = 35）。老年T2DM模型组大鼠给予高糖高脂饮食，并每天腹腔注射50 mg/kg D-半乳糖。4周后，老年T2DM模型组大鼠单次腹腔注射30 mg/kg链脲佐菌素（STZ）。注射STZ 2周后，空腹血糖（FBG）≥16.7 mmol/L定义为T2DM模型成功建立。模型成功诱导后，将30只模型大鼠根据FBG随机分为老年T2DM组（Mod）、300 mg/kg TP治疗组（TP）和3 mg/kg罗格列酮治疗组（RSG），每组10只。每组均给予50 mg/kg D-半乳糖诱导衰老，并给予高糖高脂饮食8周。实验结束时，用蛋白质免疫印迹法检测模型组腓肠肌组织中P53蛋白表达，其高于对照组，表明老年T2DM模型成功建立。用血糖仪检测FBG，计算腓肠肌相对重量，用透射电子显微镜（TEM）观察腓肠肌线粒体微观结构，用蛋白质免疫印迹法检测腓肠肌中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）和线粒体自噬相关蛋白（P62、LC3）的表达。
与对照组相比，Mod组FBG水平及P53表达升高（P<0.01）。腓肠肌相对重量、PGC-1α、OPA1表达水平及LC3II/LC3I比值降低（P<0.01）。P62和DRP1表达水平显著升高（P<0.01）。线粒体数量减少、体积减小且大量空泡化，未见明显自噬溶酶体及分裂融合现象。8周后，与Mod组相比，TP组和RSG组腓肠肌线粒体数量、空泡化、分裂融合情况改善，自噬溶酶体显著增多。TP组P53、DRP1和P62表达水平、FBG水平显著降低（P<0.01，P<·05）。OPA1和PGC-1α表达水平、LC3II/LC3I比值及腓肠肌相对重量显著升高（P<0.05，P<0.01）。
TP可改善老年T2DM模型大鼠的肌肉减少症，其机制与调节线粒体质量控制有关。
