CAJ | 학술논문

目的：观察虎杖苷（polydatin，PD）对高糖高胰岛素[（high glucose and insulin，HGI）葡萄糖25．5 mmol·L －1＋胰岛素0.1μmol·L －1]诱导心肌肥大的影响，并探讨过氧化物酶体增殖物激活受体β（peroxisome proliferator activated receptors-β，PPARβ）、核转录因子κB （nuclear transcription factor-κB，NF-κB）及一氧化氮（nitric oxide，NO）相关信号通路在其中可能存在的作用。方法体外培养乳鼠心肌细胞，以细胞表面积、蛋白含量和心房利钠因子（atrial natriuretic factor，ANF）mRNA 表达作为心肌细胞肥大反应指标；利用qRT-PCR、Western blot 法分别检测 PPARβ、NF-κB p65及诱导型一氧化氮合酶（induced nitric oxide synthase，iNOS）mR-NA 及蛋白表达，硝酸还原酶法和分光光度法分别检测 NO含量和 NOS 活性。结果HGI 作用下，细胞表面积增大、总蛋白含量增加、ANF mRNA 表达升高（P ＜0.01），出现明显的心肌肥大；同时，PPARβ表达降低，而 NF-κB p65、iNOS 表达明显升高；总 NOS 活性及 NO 含量亦增加（P ＜0.01）。PD （0.1、1、10μmol·L －1）明显抑制 HGI 诱导的心肌细胞肥大（P ＜0.01）；并逆转 HGI 对 PPARβ及 NF-κB p65、iNOS 表达和总 NOS 活性、NO 含量的影响。PPARβ选择性阻断剂GSK0660可阻断 PD 对心肌肥大的保护，取消其上述作用（P＜0.05）。结论PD 对 HGI 诱导的心肌肥大具有保护作用，其机制可能与其上调 PPARβ表达，抑制 NF-κB-iNOS-NO信号通路激活有关。
목적：관찰호장감（polydatin，PD）대고당고이도소[（high glucose and insulin，HGI）포도당25．5 mmol·L －1＋이도소0.1μmol·L －1]유도심기비대적영향，병탐토과양화물매체증식물격활수체β（peroxisome proliferator activated receptors-β，PPARβ）、핵전록인자κB （nuclear transcription factor-κB，NF-κB）급일양화담（nitric oxide，NO）상관신호통로재기중가능존재적작용。방법체외배양유서심기세포，이세포표면적、단백함량화심방리납인자（atrial natriuretic factor，ANF）mRNA 표체작위심기세포비대반응지표；이용qRT-PCR、Western blot 법분별검측 PPARβ、NF-κB p65급유도형일양화담합매（induced nitric oxide synthase，iNOS）mR-NA 급단백표체，초산환원매법화분광광도법분별검측 NO함량화 NOS 활성。결과HGI 작용하，세포표면적증대、총단백함량증가、ANF mRNA 표체승고（P ＜0.01），출현명현적심기비대；동시，PPARβ표체강저，이 NF-κB p65、iNOS 표체명현승고；총 NOS 활성급 NO 함량역증가（P ＜0.01）。PD （0.1、1、10μmol·L －1）명현억제 HGI 유도적심기세포비대（P ＜0.01）；병역전 HGI 대 PPARβ급 NF-κB p65、iNOS 표체화총 NOS 활성、NO 함량적영향。PPARβ선택성조단제GSK0660가조단 PD 대심기비대적보호，취소기상술작용（P＜0.05）。결론PD 대 HGI 유도적심기비대구유보호작용，기궤제가능여기상조 PPARβ표체，억제 NF-κB-iNOS-NO신호통로격활유관。
Aim To investigate the effect of polydatin on cardiomyocyte hypertrophy induced by high glucose (25.5 mmol·L -1 )and insulin (0.1 μmol ·L -1 ) (HGI)and its possible influence on peroxisome prolif-erator-activated receptor-β (PPARβ)/nuclear tran-scription factor-κB (NF-κB)/nitric oxide (NO)signa-ling pathway.Methods The cardiomyocyte hypertro-phy was characterized in rat primary cardiomyocytes by measuring the cell surface area,protein content,and atrial natriuretic factor (ANF)mRNA expression.The mRNA and protein expressions were measured by qRT-PCR and Western blotting,respectively.The activity of NO synthase (NOS)and NO content were measured by reagent kit through ultraviolet spectroscopy.Results HGI significantly induced cardiomyocyte hypertrophy which increased the cell surface area,protein content and ANF mRNA expression (P <0.01 ).Meanwhile, the expressions of PPARβmRNA and protein reduced while the NF-κB p65 and iNOS expressions increased significantly which occurred in parallel with rising NOS activity and NO concentration (P <0.01 ).Polydatin (0.1,1,10 μmol·L -1 )inhibited the cardiomyocyte hypertrophy induced by HGI (P <0.01 ),and re-versed the mRNA and protein expressions of PPARβ, NF-κB p65 and iNOS,and NOS activity,as well as NO content.These effects of polydatin were abolished by GSK0660 (1 μmol·L -1 ),a selective PPARβan-tagonist (P <0.05 ).Conclusion Polydatin resists HGI-induced cardiomyocyte hypertrophy,which may be mediated by PPARβup-regulation,and then NF-κB-iNOS-NO pathway inactivation.