基于GS/βAR/cAMP/PKA信号通路探讨蜂胶总黄酮对心肌肥厚大鼠的保护作用及分子机制  

Protective effects and molecular mechanism of total flavonoids of propolis on myocardial hypertrophy in rats based on GS/βAR/cAMP/PKA signaling pathway

作　　者：阚默 明思彤 张壮 刘晓冉 王继凤 林嘉楠[1] 杨擎[1] 石晓征[1] 李晶[1] 隋欣[1] 李娜[1] 林喆[1] KAN Mo;MING Si-tong;ZHANG Zhuang;LIU Xiao-ran;WANG Ji-feng;LIN Jia-nan;YANG Qing;SHI Xiao-zheng;LI Jing;SUI Xin;LI Na;LIN Zhe(Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学,长春130117

出　　处：《中华中医药杂志》2021年第6期3235-3239,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：吉林省中医药管理局项目(No.〔2019〕91)。

摘　　要：目的:基于GS/βAR/cAMP/PKA信号通路探讨蜂胶总黄酮(TFP)对异丙肾上腺素(ISO)诱导心肌肥厚大鼠保护作用及分子机制。方法:将50只SD大鼠随机分为空白组(Control)组、模型组(ISO组)、阳性组(Positive组)及蜂胶总黄酮低、高剂量组(TFPL组、TFPH组)。TFPL组、TFPH组大鼠分别灌胃TFP 25、100mg/kg,灌胃14d;Positive组灌胃复方丹参片290mg/kg,灌胃14d;其余组灌胃相同剂量的0.9%氯化钠溶液。第8天除Control组外,其余组均皮下注射ISO 7d建立心肌肥厚模型。观察记录大鼠状态并绘制生长曲线;流式细胞术检测心肌细胞凋亡情况;HE、Masson染色观察心脏病理情况;检测血清中TG、T-CHO、LDL-C、HDL-C以及ATP含量;Western blot法检测GS/βAR/cAMP/PKA信号通路相关蛋白表达情况。结果:TFPH组可显著降低心肌细胞总凋亡率(P<0.01),缓解心肌肥厚大鼠心肌损伤,改善心肌结构,抑制胶原纤维化;降低心肌肥厚大鼠血清中TG、T-CHO、LDL-C含量,升高HDL-C、ATP含量(P<0.05);心肌组织中GS/βAR/cAMP/PKA信号通路相关蛋白表达水平显著上升(P<0.01,P<0.05)。结论:TFP对ISO诱导心肌肥厚大鼠具有一定的保护作用,抑制心肌纤维化,降低心肌细胞凋亡,其作用机制与激活GS/βAR/cAMP/PKA信号通路相关蛋白表达有关。Objective:Based on the GS/βAR/cAMP/PKA signaling pathway,to investigate the protective effects and molecular mechanism of total flavonoids of propolis(TFP)on isoproterenol(ISO)-induced myocardial hypertrophy in rats.Methods:Fifty SD rats were randomly divided into blank group(Control group),model group(ISO group),positive group,low and high doses of propolis total flavonoids(TFPL group,TFPH group).TFPL group and TFPH group were intragastrically administered with TFP at doses of 25 and 100mg/kg for 14d;Positive group was intragastrically administered with Fufang Danshen Tablets at a dose of 290mg/kg for 14d.The other groups were intragastrically administered with the same dose of 0.9%sodium chloride solution.On the 8th day,except for the control group,the other groups were given subcutaneous injection of ISO for 7d to establish cardiac hypertrophy model.The state of rats and draw growth curves were observed and recorded;flow cytometry to detect cardiomyocyte apoptosis;HE and Masson staining to observe cardiology;serum TG,T-CHO,LDL-C,HDL-C and ATP content were detected;Western blot was used to detect the expression of related proteins in the GS/βAR/cAMP/PKA signaling pathway.Results:TFPH group significantly reduced the total apoptotic rate of cardiomyocytes(P<0.01);relieved myocardial injury in rats with myocardial hypertrophy,improved myocardial structure,and inhibited collagen fibrosis;reduced serum TG,T-CHO,and LDL-C in rats with myocardial hypertrophy content,increased HDL-C and ATP content(P<0.05);GS/βAR/cAMP/PKA signaling pathway related protein expression levels in the myocardial tissue of TFPH group were significantly increased(P<0.01,P<0.05).Conclusion:TFP has a certain protective effect on ISO-induced myocardial hypertrophy in rats,inhibits myocardial fibrosis,and reduces myocardial cell apoptosis.Its mechanism of action is related to the activation of GS/βAR/cAMP/PKA signaling pathway related protein expression.

关 键 词：蜂胶总黄酮 异丙肾上腺素 心肌肥厚 GS/βAR/cAMP/PKA信号通路 

分 类 号：R285.5[医药卫生—中药学]