首页|归脾汤对5-FU诱导的化疗相关性疲劳模型氧化应激和线粒体自噬蛋白的影响

归脾汤对5-FU诱导的化疗相关性疲劳模型氧化应激和线粒体自噬蛋白的影响

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目的 探讨归脾汤对化疗相关性疲劳(CIF)模型骨骼肌氧化应激和线粒体自噬相关蛋白表达的影响。方法 将48只SPF级SD大鼠随机分为空白组,模型组,归脾汤低剂量组,归脾汤高剂量组,每组12只。将除空白组以外的大鼠腹腔注射5-氟尿嘧啶(5-FU),剂量为28mg/kg,每天给药一次,连续5d。在造模的同时归脾汤组给予不同剂量归脾汤灌胃,其余组灌胃生理盐水,期间测量体质量及抓力。第12天处死动物取腓肠肌并提取线粒体,测ROS含量和线粒体膜电位,Western Blot法检测Parkin、OPTN、NDP52和USP30的表达情况。结果 与空白组相比,模型组抓力显著下降(P<0。05),ROS显著升高(P<0。01),线粒体膜电位显著降低(P<0。01),归脾汤组抓力显著高于模型组(P<0。01),线粒体膜电位显著高于模型组(P<0。01),ROS显著低于模型组(均P<0。01)。Western Blot结果显示模型组的Parkin、OPTN、NDP52蛋白表达显著下降(P<0。01),USP30的表达显著升高(P<0。01);而归脾汤可显著上调Parkin、OPTN、NDP52的蛋白表达(P<0。01)和显著下调USP30蛋白的表达。结论 归脾汤可通过减轻骨骼肌线粒体的氧化应激损伤以及影响线粒体自噬蛋白的表达从而改善CIF。
Effects of Guipi Decoction on oxidative stress and mitophagy related proteins in CIF mod-el induced by 5-FU
Objective To investigate the effects of Guipi Decoction on oxidative stress in skeletal muscle and expression of mito-phagy related proteins in chemotherapy induced fatigue(CIF)model.Methods Forty-eight SPF SD rats were randomly divided into normal group,model group,low dose Guipi Decoction group(GPD group)and high dose Guipi Decoction group.Rats were in-traperitoneally injected 5-fluorouracil(5-FU)at a dose of 28mg/kg once a day for 5 consecutive days.At the same time,Guipi Decoction was gavaged to the rats of GPD groups,and the other groups were given saline.Body weight and grip strength were measured during the experimental period.On the 12nd day,the gastrocnemius muscle was taken from the sacrificed rats and mito-chondria were extracted to detect ROS content and mitochondrial membrane potential,as well as the expressions of Parkin,OPTN,NDP52 and USP30 by Western Blot.Results Compared with normal group,grip strength in model group significantly decreased(P<0.05),ROS significantly increased(P<0.01),and mitochondrial membrane potential significantly decreased(P<0.01).Grip strength in GPD group was significantly higher than that in model group(P<0.01),mitochondrial membrane po-tential was significantly higher than that in model group(P<0.01),ROS was significantly lower than model group(all P<0.01).Western Blot results showed that the expression of Parkin,OPTN and NDP52 in model group significantly decreased(P<0.01),while the expression of USP30 significantly increased(P<0.01).GPD could significantly up-regulate Parkin,OPTN,NDP52 protein expression(P<0.01)and down-regulate USP30 protein expression.Conclusion GPD can improve CIF by re-ducing oxidative stress injury of skeletal muscle mitochondria and affecting the expression of mitophagy proteins.

ChemotherapyFatigueOxidative stressMitophagyGuipi Decoction

雷萍、宋予馨、许欣竹、韩晓伟、董墨思、徐铭、王建光

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辽宁中医药大学,辽宁沈阳 110847

化疗 疲劳 氧化应激 线粒体自噬 归脾汤

2024

时珍国医国药
时珍国医国药杂志社

时珍国医国药

北大核心
影响因子:0.887
ISSN:1008-0805
年,卷(期):2024.35(3)