心脏纤维化是遗传性和获得性心血管疾病(Cardiovascular Disease, CVD)的最终常见病理,导致功能和电生理异常,并同时参与了各种疾病的发展与转归,长期以来一直被视为一种治疗靶点。现有多项研究证实转化生长因子-β (Transforming Growt...心脏纤维化是遗传性和获得性心血管疾病(Cardiovascular Disease, CVD)的最终常见病理,导致功能和电生理异常,并同时参与了各种疾病的发展与转归,长期以来一直被视为一种治疗靶点。现有多项研究证实转化生长因子-β (Transforming Growth Factor β, TGF-β)与下游Smad家族所介导的纤维化在心脏纤维化中起着关键作用。以此通路为靶点的中医药研究是目前逆转心脏纤维化的热点。因此,文章以TGF-β1/Smads信号通路为线索,概述近年来中药复方及单味药提取物干预该通路和上下游相关因子,以达到逆转心脏纤维化的作用机制,借以阐明中医药靶向治疗的作用及机制。Cardiac fibrosis is the ultimate common pathology of inherited and acquired cardiovascular disease (CVD), resulting in functional and electrophysiological abnormalities, and is simultaneously involved in the development and outcome of various diseases and has long been regarded as a therapeutic target. A number of studies have confirmed that transforming growth factor β (TGF-β) and downstream Smad family-mediated fibrosis plays a key role in cardiac fibrosis. Currently, the research of traditional Chinese medicine targeting this pathway focuses on reversing cardiac fibrosis. Therefore, in this paper, TGF-β1/Smads signaling pathway clues were used to summarize the mechanism of intervention of TCM compounds and single drug extracts in this pathway and related upstream and downstream factors in recent years to reverse cardiac fibrosis, so as to clarify the role and mechanism of targeted therapy of traditional Chinese medicine.展开更多
目的通过观察瓜蒌薤白半夏汤对心肌缺血模型大鼠心肌组织病理变化的影响,探讨其对心肌细胞外基质(ECM)重构的干预作用。方法70只SD大鼠随机选取10只为对照组,余下大鼠造模成功后随机分为模型组,瓜蒌薤白半夏汤低、中、高剂量组及美托洛...目的通过观察瓜蒌薤白半夏汤对心肌缺血模型大鼠心肌组织病理变化的影响,探讨其对心肌细胞外基质(ECM)重构的干预作用。方法70只SD大鼠随机选取10只为对照组,余下大鼠造模成功后随机分为模型组,瓜蒌薤白半夏汤低、中、高剂量组及美托洛尔组,持续给药28 d。干预结束后取材,HE和Masson染色观察大鼠心肌组织病理学变化及纤维化程度;免疫组化检测α-平滑肌肌动蛋白(α-SMA)的阳性表达水平;比色法测定血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)以及乳酸脱氢酶(LDH)的含量;ELISA检测血清N-末端B型利钠肽前体(NT-proBNP)及转化生长因子(TGF)-β1的含量;Western blot法检测心肌组织TGF-β1、Smad2和Smad3蛋白相对表达水平;RT-qPCR检测COL1A1和FN m RNA表达水平。结果与模型组比较,瓜蒌薤白半夏汤高剂量组心肌组织病理显示出现不同程度改善,心肌纤维排列有序,细胞界限清晰,仍有轻微间隙增宽,并伴有少量炎性细胞浸润,胶原容积分数(CVF)显著降低(P<0.01);α-SMA阳性表达平均光密度值(MOD)显著降低(P<0.01);血清CK、CK-MB、LDH、NT-proBNP以及TGF-β1水平显著降低(P<0.01);TGF-β1、Smad2和Smad3蛋白表达水平显著降低(P<0.01);COL1A1和FN m RNA表达水平显著降低(P<0.01)。结论瓜蒌薤白半夏汤显著减轻心肌缺血模型大鼠的心肌病理形态变化和纤维化程度,改善心脏功能,其机制可能与通过调控TGF-β1/Smads信号通路抑制心肌ECM重构相关。展开更多
文摘心脏纤维化是遗传性和获得性心血管疾病(Cardiovascular Disease, CVD)的最终常见病理,导致功能和电生理异常,并同时参与了各种疾病的发展与转归,长期以来一直被视为一种治疗靶点。现有多项研究证实转化生长因子-β (Transforming Growth Factor β, TGF-β)与下游Smad家族所介导的纤维化在心脏纤维化中起着关键作用。以此通路为靶点的中医药研究是目前逆转心脏纤维化的热点。因此,文章以TGF-β1/Smads信号通路为线索,概述近年来中药复方及单味药提取物干预该通路和上下游相关因子,以达到逆转心脏纤维化的作用机制,借以阐明中医药靶向治疗的作用及机制。Cardiac fibrosis is the ultimate common pathology of inherited and acquired cardiovascular disease (CVD), resulting in functional and electrophysiological abnormalities, and is simultaneously involved in the development and outcome of various diseases and has long been regarded as a therapeutic target. A number of studies have confirmed that transforming growth factor β (TGF-β) and downstream Smad family-mediated fibrosis plays a key role in cardiac fibrosis. Currently, the research of traditional Chinese medicine targeting this pathway focuses on reversing cardiac fibrosis. Therefore, in this paper, TGF-β1/Smads signaling pathway clues were used to summarize the mechanism of intervention of TCM compounds and single drug extracts in this pathway and related upstream and downstream factors in recent years to reverse cardiac fibrosis, so as to clarify the role and mechanism of targeted therapy of traditional Chinese medicine.
文摘目的通过观察瓜蒌薤白半夏汤对心肌缺血模型大鼠心肌组织病理变化的影响,探讨其对心肌细胞外基质(ECM)重构的干预作用。方法70只SD大鼠随机选取10只为对照组,余下大鼠造模成功后随机分为模型组,瓜蒌薤白半夏汤低、中、高剂量组及美托洛尔组,持续给药28 d。干预结束后取材,HE和Masson染色观察大鼠心肌组织病理学变化及纤维化程度;免疫组化检测α-平滑肌肌动蛋白(α-SMA)的阳性表达水平;比色法测定血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)以及乳酸脱氢酶(LDH)的含量;ELISA检测血清N-末端B型利钠肽前体(NT-proBNP)及转化生长因子(TGF)-β1的含量;Western blot法检测心肌组织TGF-β1、Smad2和Smad3蛋白相对表达水平;RT-qPCR检测COL1A1和FN m RNA表达水平。结果与模型组比较,瓜蒌薤白半夏汤高剂量组心肌组织病理显示出现不同程度改善,心肌纤维排列有序,细胞界限清晰,仍有轻微间隙增宽,并伴有少量炎性细胞浸润,胶原容积分数(CVF)显著降低(P<0.01);α-SMA阳性表达平均光密度值(MOD)显著降低(P<0.01);血清CK、CK-MB、LDH、NT-proBNP以及TGF-β1水平显著降低(P<0.01);TGF-β1、Smad2和Smad3蛋白表达水平显著降低(P<0.01);COL1A1和FN m RNA表达水平显著降低(P<0.01)。结论瓜蒌薤白半夏汤显著减轻心肌缺血模型大鼠的心肌病理形态变化和纤维化程度,改善心脏功能,其机制可能与通过调控TGF-β1/Smads信号通路抑制心肌ECM重构相关。
