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      川芎嗪對血管內(nèi)皮損傷的保護作用機制研究進展

      2020-04-27 13:18:47李芳芳張琪
      中國醫(yī)藥導報 2020年8期
      關鍵詞:川芎嗪氧化應激

      李芳芳 張琪

      [摘要] 血管內(nèi)皮的受損程度與高血壓等心血管疾病的發(fā)展進程密切相關。高血壓、冠心病以及動脈粥樣硬化等多種心血管疾病均會出現(xiàn)不同程度的血管內(nèi)皮損傷,保護損傷的內(nèi)皮細胞是心血管疾病防治的關鍵。川芎嗪是從中草藥川芎中提取的一種生物堿,具有生物活性和多種藥理作用。其藥理作用包括延緩內(nèi)皮細胞凋亡、促進血管新生、抗炎、抗氧化等,可用于治療高血壓病引起的血管結(jié)構(gòu)和功能的改變。本文綜述了川芎嗪抗高血壓病血管內(nèi)皮損傷的作用機制及其研究進展,為川芎嗪治療心腦血管病的臨床應用提供科學依據(jù)。

      [關鍵詞] 川芎嗪;血管內(nèi)皮損傷;血管新生;氧化應激

      [中圖分類號] R965? ? ? ? ? [文獻標識碼] A? ? ? ? ? [文章編號] 1673-7210(2020)03(b)-0025-04

      [Abstract] The degree of vascular endothelial injury is closely related to the development of cardiovascular diseases such as hypertension. Many kinds of cardiovascular diseases, such as hypertension, coronary heart disease and atherosclerosis, will present different degrees of vascular endothelial injury, and the protection of injured endothelial cells is the key to the prevention and treatment of cardiovascular diseases. Tetramethylpyrazine is a kind of alkaloid extracted from Chinese herbal medicine Ligusticum chuanxiong Hort.. It has biological activity and many pharmacological effects. Its pharmacological effects include, delaying endothelial cell apoptosis, promoting angiogenesis, anti-inflammatory, antioxidant, etc. It can be used to treat the changes in vascular structure and function caused by hypertension. This article reviews the research progress of Tetramethylpyrazine against vascular endothelial injury in hypertension, and provides scientific basis for the clinical application of Tetramethylpyrazine in the treatment of cardiovascular and cerebrovascular diseases.

      [Key words] Tetramethylpyrazine; Vascular endothelial injury; Angiogenesis; Oxidative stress

      高血壓病屬于心血管系統(tǒng)的常見病,是一種受多種要素影響的慢性階段性疾病,具有較高的發(fā)病率和致死率,持續(xù)性高血壓容易導致血管功能病變以及血管結(jié)構(gòu)病變。血管內(nèi)皮細胞位于血管內(nèi)面,是一層扁平上皮細胞,具有調(diào)節(jié)血管通透性與緊張性、凝血與抗凝血、平滑肌增殖與遷移的作用,并參與免疫反應,且能分泌多種生長因子,對于血管功能的正常發(fā)揮至關重要[1-2]。血管內(nèi)皮受損后,其分泌功能和屏障作用會減弱,高血壓、冠心病、動脈粥樣硬化等多種心血管疾病均會出現(xiàn)血管內(nèi)皮損傷。血管內(nèi)皮損傷的機制主要涉及血管舒縮狀態(tài)失衡、內(nèi)皮細胞凋亡、血管新生、炎癥、氧化應激等。

      川芎(Ligusticum chuanxiong Hort.)最早記載于《神農(nóng)本草經(jīng)》,屬傘形科植物,臨床應用歷史悠久。川芎嗪(2,3,5,6-四甲基吡嗪,Tetramethylpyrazine,TMP)是川芎的主要有效成分之一,是從其根莖中提取的一種活性生物堿,TMP在我國已廣泛應用于治療高血壓等心血管疾病[3]。研究顯示,TMP具有延緩細胞凋亡、促進血管新生、抗炎、抗氧化等多種藥理作用[4-5]。為了進一步研究TMP抗血管內(nèi)皮損傷的作用機制,本文重點綜述了TMP抗血管內(nèi)皮損傷的作用機制以及研究進展,為臨床合理用藥提供科學依據(jù)。

      1 一氧化氮(NO)與內(nèi)皮素(ET)

      血管內(nèi)皮細胞可參與合成并分泌多種活性物質(zhì),最主要的有NO和ET-1,其可調(diào)節(jié)血管的舒縮狀態(tài)。在生理狀態(tài)下,ET與NO始終保持著平衡,從而維持血管的正常舒縮,是體現(xiàn)血管內(nèi)皮功能的代表性指標[6]。高血壓病在發(fā)展過程中,ET與NO失衡,血管收縮占據(jù)了主導地位,從而使血壓升高,造成血管內(nèi)皮功能損害。有研究顯示,TMP能夠使ET與NO維持動態(tài)平衡,F(xiàn)eng等[7]發(fā)現(xiàn)TMP可使肺動脈高壓患者血漿中的NO水平上升,ET-1水平下降。TMP可使缺氧誘導的人臍靜脈內(nèi)皮細胞(HUVECs)損傷的ET水平下降,NO水平上升,進而調(diào)節(jié)血管舒縮功能[8]。Li等[9]通過建立大鼠慢性酒精性腦病模型,發(fā)現(xiàn)TMP可降低ET-1水平,還可以增加血管內(nèi)皮生長因子(VEGF)表達,提高學習能力,這些結(jié)果提示,TMP對慢性酒精性腦病的治療作用可能與調(diào)節(jié)ET-1水平和VEGF表達有關。方浩[10]研究顯示,TMP通過下調(diào)ET-1水平進而保護妊娠期高血壓患者血管內(nèi)皮細胞。TMP可通過影響環(huán)磷酸鳥苷(cGMP)的分泌進一步影響血管內(nèi)皮細胞釋放NO,從而舒張血管[11]。TMP通過下調(diào)ET水平和上調(diào)NO水平來平衡血管舒縮狀態(tài)。

      6 小結(jié)

      中草藥川芎,在我國已應用上千年,臨床應用極其廣泛,臨床療效確切。川芎的主要成分TMP,在當代藥理研究中,應用廣泛,價值極高。TMP保護血管內(nèi)皮損傷的作用機制可能與平衡血管舒縮狀態(tài)、延緩內(nèi)皮細胞凋亡、促進血管新生、抗炎、抗氧化等多種作用有關。盡管對TMP的現(xiàn)代藥理作用研究眾多,相對深入,也有對其衍生物及與其他藥物聯(lián)合應用的報道,但相對較少,機制尚不明確。應加強這些方面的研究工作,開發(fā)出藥效更好、穩(wěn)定性更強的TMP使用制劑,進一步詳細闡明TMP保護血管內(nèi)皮損傷的機制,為TMP在臨床治療心腦血管病方面提供更加科學有效的依據(jù)。

      [參考文獻]

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      (收稿日期:2019-09-04? 本文編輯:封? ?華)

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