基于TGF-β/Smad信号通路探讨白参和黑参防治心肌肥厚的作用与机制  

Effects and mechanisms of White ginseng and Black ginseng on prevention and treatment of cardiac hypertrophy based on TGF-β/Smad signaling pathway

作　　者：曹占鸿 阚俊明[1] 张艳红 庞其杭 江俊杰 刘雅鑫 李辉[2] 徐可进[1] 李祯 林嘉楠[1] 杨擎 李娜 CAO Zhan-hong;KAN Jun-ming;ZHANG Yan-hong;PANG Qi-hang;JIANG Jun-jie;LIU Ya-xin;LI Hui;XU Ke-jin;LI Zhen;LIN Jia-nan;YANG Qing;LI Na(Changchun University of Chinese Medicine,Changchun 130117,China;Qian Wei Hospital of Jilin Province,Changchun 130012,China)

机构地区：[1]长春中医药大学,长春130117 [2]吉林省前卫医院,长春130012 [3]长春中医药大学人参科学研究院

出　　处：《中华中医药杂志》2022年第5期2569-2574,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：吉林省科技厅项目(No.20200708056YY);吉林省科技发展计划项目(No.20210204086YY);吉林省教育厅科学研究项目(No.JJKH20220884KJ)。

摘　　要：目的:基于转化生长因子-β(TGF-β)/Smad信号通路探讨白参和黑参水煎液对心肌肥厚大鼠的保护作用及机制。方法:高效液相色谱法和苯酚-硫酸法测定两种水煎液中人参皂苷和人参多糖含量;异丙肾上腺素(ISO)皮下注射制备心肌肥厚大鼠模型,观察对心肌肥厚大鼠体质量、心重指数的影响;超声心动图评价心肌肥厚大鼠心功能;HE、Masson染色评价心肌肥厚大鼠心肌形态及纤维化程度;检测血清中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、脑钠肽(BNP)和羟脯氨酸(HYP)水平,并采用灰色关联度分析方法分析两种水煎液中皂苷和多糖与血清生化指标的关系;Western Blot检测TGF-β/Smad信号通路相关蛋白表达水平。结果:白参水煎液中10种皂苷总量高于黑参水煎液,而多糖含量则趋势相反;两种水煎液均可提高心肌肥厚大鼠体质量增长速度,降低心重指数(P<0.05);改善心功能(P<0.01,P<0.05);改善心肌组织形态结构,降低心肌纤维化程度;降低血清中AngⅡ、ALD、BNP和HYP含量(P<0.01,P<0.05);灰色关联度分析结果表明人参皂苷(R)-Rh1对ALD和BNP贡献度最大,人参皂苷Rg2对AngⅡ和HYP贡献度最大;两种水煎液均可抑制TGF-β1、Smad4和TIMP1蛋白表达水平(P<0.01,P<0.05),增加Smad7和MMP9蛋白表达(P<0.01,P<0.05)。结论:两种水煎液可能通过抑制RAAS系统激活,阻断TGF-β/Smad信号通路,降低心肌组织纤维化程度,对ISO诱导的心肌肥厚大鼠起到保护作用,黑参效果优于白参。Objective:To investigate the protective effects and mechanisms of water extracts of White ginseng and Black ginseng on myocardial hypertrophy rats based on TGF-β/Smad signaling pathway.Methods:HPLC and phenol-sulfuric acid method were used to determine the contents of ginsenosides and polysaccharide in two kinds of water decoctions.The rat model of myocardial hypertrophy was established by subcutaneous injection of isoprenaline(ISO),and the effects on body weight and cardiac index of rats with myocardial hypertrophy were observed.Echocardiography was used to evaluate cardiac function in rats with myocardial hypertrophy;HE and Masson staining were used to evaluate myocardial morphology and degree of fibrosis in rats with myocardial hypertrophy.The contents of AngⅡ,ALD,BNP and HYP in serum were detected,and the grey correlation analysis was used to study the relationship between ginsenosides,polysaccharides and serum biochemical indexes.Western Blot was used to detect TGF-β/Smad signaling pathway related protein expression levels.Results:The total amount of 10 kinds of ginsenosides in White ginseng decoction was higher than that in Black ginseng decoction,while the content of polysaccharide showed the opposite trend.Both of the two kinds of decoction could increase the growth rate of body weight and decrease the heart weight index of rats with myocardial hypertrophy(P<0.05),improve cardiac function(P<0.01,P<0.05),improve the morphology and structure of myocardial tissue,reduce the degree of myocardial fibrosis,and reduce the contents of Ang II,ALD,BNP and HYP in serum(P<0.01,P<0.05).The results of grey correlation analysis showed that(R)-Rh1 had the greatest contribution to ALD and BNP,and Rg2 had the greatest contribution to AngⅡand HYP.The decoction of White ginseng and Black ginseng could inhibit the expression of TGF-β1,Smad4 and TIMP1(P<0.01,P<0.05),and increase the expression of Smad7 and MMP9(P<0.01,P<0.05).Conclusion:The two decoctions may inhibit the activation of the RAAS system,block the TGF-β/Sm

关 键 词：白参 黑参 皂苷 多糖 心肌肥厚 TGF-Β/SMAD RAAS系统 异丙肾上腺素 

分 类 号：R285.5[医药卫生—中药学]