首页|黄芪建中汤对心源性恶病质大鼠白色脂肪消耗及BMAL1/REV-ERBα节律环路的影响

黄芪建中汤对心源性恶病质大鼠白色脂肪消耗及BMAL1/REV-ERBα节律环路的影响

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目的 探究黄芪建中汤对心源性恶病质大鼠白色脂肪组织(WAT)过度消耗的影响以及BMAL1/REV-ERBα 节律环路在其中的作用.方法 将40只Dahl盐敏感大鼠随机分为对照组、正常节律组、正常节律中药组、颠倒节律组、颠倒节律中药组,每组8只,除对照组外其余各组均饲喂高盐饲料(8%NaCl)以诱导心源性恶病质;颠倒节律组、颠倒节律中药组在昼夜颠倒条件下饲养,其余各组则置于正常光暗条件下饲养.记录各组大鼠心功能和体质量,HE、油红染色观察WAT病理形态学改变,免疫组化检测WAT中UCP1表达,Western blot法检测WAT中HSL、PKA、p-PKA、BMAL1、REV-ERBα 蛋白表达.结果 与对照组比较,正常节律组大鼠心功能及体质量均降低(P<0.05),WAT油红染色阳性面积以及脂肪细胞内径均降低(P<0.01),UCP1蛋白阳性面积增加(P<0.01),WAT中HSL、PKA、p-PKA、REV-ERBα蛋白表达升高(P<0.05);与正常节律组比较,颠倒节律组WAT油红染色阳性面积以及脂肪细胞内径均降低(P<0.05),WAT中HSL、PKA、p-PKA、REV-ERBα蛋白表达升高(P<0.05),BMAL1蛋白表达降低(P<0.05);与正常节律组和颠倒节律组比较,黄芪建中汤干预后,WAT油红染色阳性面积以及脂肪细胞内径均升高(P<0.05),UCP1蛋白阳性面积减少(P<0.01),WAT中HSL、PKA、p-PKA、REV-ERBα蛋白表达均降低(P<0.05),BMAL1蛋白表达升高(P<0.05).结论 黄芪建中汤可能通过调节BMAL1/REV-ERBα 节律环路,减缓白色脂肪水解和棕色化,从而减轻心源性恶病质过量的脂肪消耗.
Effects of Huangqi Jianzhong Decoction on white adipose tissue consumption and circadian rhythm genes of BMAL1/REV-ERBα in a rat model of cardiac cachexia
AIM To investigate the effects of the Chinese medicine of Huangqi Jianzhong Decoction on excessive consumption of white adipose tissue (WAT) in a rat model of cardiac cachexia and the role of BMAL1/REV-ERBα circadian loop in WAT.METHODS Forty Dahl salt-sensitive rats were randomly divided into the control group,the normal circadian rhythm group,the normal circadian rhythm+Chinese medicine group,the mass recorded;their pathomorphological changes of WAT observed using HE and oil red staining;their UCP1 expression in WAT detected by immunohistochemistry;and their protein expression of HSL,PKA,p-PKA,BMAL1 and REV-ERBα in WAT detected by Western blot.RESULTS Compared with the control group,the normal rhythm group showed decreased rat cardiac function and body weight (P<0.05);decreased positive area of oil red staining in WAT and the inner diameter of adipocytes (P<0.01);increased positive area of UCP1 protein (P<0.01),and increased expressions of HSL,PKA,p-PKA and REV-ERBαprotein in WAT as well (P<0.01).Compared with the normal rhythm group,the disrupted circadian rhythm group displayed decreased positive area of oil red staining of WAT and the inner diameter of adipocytes (P<0.05),increased expressions of HSL,PKA,p-PKA and REV-ERBαin WAT (P<0.05),and decreased BMAL1 protein expression (P<0.05).Upon both groups of normal rhythm and disrupted circadian rhythm,the intervention of Huangqi Jianzhong Decoction increased the positive area of oil red staining in WAT and the inner diameter of adipocytes (P<0.05),decreased the positive area of UCP1 protein (P<0.01),decreased the expressions of HSL,PKA,p-PKA and REV-ERBα protein in WAT (P<0.05),and increased the expression of BMAL1 protein (P<0.05).CONCLUSION Huangqi Jianzhong Decoction may alleviate the excessive WAT depletion in the rat model of cardiac cachexia through reduction in adipose tissue dialysis and browning of white adipocytes via regulation of the circadian rhythm genes of BMAL1/REV-ERBα.

Huangqi Jianzhong Decoctioncardiac cachexiafat consumptioncircadian rhythm loopbrowning of white fat

吴涛、曲一玮、徐圣洁、李晓、王咏、马度芳

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山东中医药大学中医学院,山东 济南 250000

山东中医药大学第一临床医学院,山东 济南250000

山东中医药大学附属医院,山东 济南250014

黄芪建中汤 心源性恶病质 脂肪消耗 昼夜节律环路 白色脂肪棕色化

2024

中成药
国家食品药品监督管理局,信息中心中成药信息站,上海中药行业协会

中成药

CSTPCD北大核心
影响因子:1.217
ISSN:1001-1528
年,卷(期):2024.46(12)