邱伯雍 邢作英 朱明軍 王永霞
摘要 ?中醫(yī)藥可改善心力衰竭病人癥狀,提高生活質量,降低再住院率和全因死亡率。中醫(yī)通過抗心肌缺血、心肌凋亡、心肌纖維化、炎癥反應、氧化應激、腎素.血管緊張素.醛固酮系統(tǒng)以及促進血管生成、調節(jié)能量代謝和腸道菌群等,發(fā)揮抗心力衰竭作用。綜述治療心力衰竭的中藥新藥進展,對中醫(yī)藥治療心力衰竭作用機制進行探討,以期為心力衰竭的研究提供借鑒。
關鍵詞 ?心力衰竭;中醫(yī)藥;作用機制;研究進展;綜述
doi: ?10.12102/j.issn.1672.1349.2024.10.012
慢性心力衰竭在世界范圍內的流行正在擴大,治療心力衰竭是心血管領域的巨大挑戰(zhàn),亦是醫(yī)學現(xiàn)代化面臨的難題 ?[1.3] 。數(shù)千年來,中醫(yī)藥一直廣泛應用于心力衰竭的臨床治療,獨具優(yōu)勢 ?[4] ,辨證的個體化用藥 ?[5] ,多靶點整體治療 ?[6.7] ,緩解胸悶、氣短、乏力、水腫等癥狀 ?[8.9] ,提高生活質量,增強免疫力,降低藥物毒副作用 ?[10] 等。近年來,醫(yī)學家們開展了廣泛的研究探索中藥治療心力衰竭的作用機制?,F(xiàn)對治療心力衰竭的中藥新藥進展及作用機制進行總結并探討。
1 治療心力衰竭中藥新藥
中醫(yī)與現(xiàn)代科技的結合使其發(fā)揮新優(yōu)勢,中醫(yī)藥治療心力衰竭的研究正在大規(guī)模地展開,證據(jù)基礎不斷擴增,加快了中醫(yī)治療心力衰竭的發(fā)展。在中醫(yī)理論指導下挖掘中醫(yī)經(jīng)典方藥,從生物學、藥理學、計算機科學及現(xiàn)代工藝等多科學研究,促使中醫(yī)藥治療心力衰竭取得新突破。基于中醫(yī)經(jīng)典名方、名醫(yī)經(jīng)驗、中醫(yī)新理論、膏方理論、現(xiàn)代藥理研究及新制作工藝等,從中醫(yī)學寶庫中挖掘出防治心力衰竭的中藥新藥,品類多樣、功效獨特、適用范圍廣泛,包括膠囊劑、丸劑、片劑、膏劑、口服液劑和靜脈制劑等,顯著提高了慢性心力衰竭病人的生活質量,改善心功能和臨床癥狀,降低病死率。詳見表1。心力衰竭慢性期除丸散外還可選用膏劑,防治結合,口感頗佳,病人依從性好,可長期服用 ?[11] 。靜脈制劑多用于心力衰竭急性加重期,研究表明,聯(lián)合中藥效果優(yōu)于純西醫(yī)治療 ?[12] ,如參麥注射液、生脈注射液、參附注射液在降低N末端腦鈉肽前體(NT.proBNP)、腦鈉肽在提高臨床總有效率方面具有優(yōu)勢;參麥注射液、丹紅注射液、生脈注射液在提高心臟泵血功能方面更具優(yōu)勢;參麥注射液、生脈注射液、益氣復脈注射液在總體療效及改善單項指標方面均有明確優(yōu)勢。
2 中藥治療心力衰竭的作用機制
心臟負荷過載后出現(xiàn)心室擴大、心肌肥厚、心肌收縮力及心室順應性下降等,導致并加速心室重塑。因此,保護心肌功能和延緩心室重塑是中藥治療心力衰竭的重要研究方向。中藥通過抗心肌缺血、心肌纖維化、炎癥、氧化應激、凋亡,促血管生成,抑制腎素.血管緊張素.醛固酮系統(tǒng)(RAAS),調節(jié)能量代謝及腸道菌群等多維途徑改善心室重構,進而發(fā)揮抗心力衰竭的作用。詳見表2。芪參益氣滴丸調節(jié)心肌纖維化 ?[27] 、氧化應激和能量代謝 ?[28] 、RAAS ?[29] 、血管生長 ?[30] 、炎癥 ?[31] 、凋亡 ?[32] 等;四逆湯 ?[33.35] 改善心功能、抗纖維化和炎癥、抑制RAAS;芪藶強心膠囊 ?[36.38] 抗纖維化、凋亡、炎癥和心肌肥大等。
中醫(yī)學認為“心與小腸相表里”,調節(jié)腸道功能可作為治療心血管疾病的新靶點,心腸軸可能成為今后中醫(yī)治療心力衰竭的研究方向 ?[39] 。腸道微生物代謝物包括三甲胺、膽汁酸、益生菌和微生物酶等,通過細菌易位等多種代謝途徑影響人體代謝及心臟功能,發(fā)揮治療心力衰竭的作用 ?[40.41] 。參附注射液通過增加短鏈脂肪酸產(chǎn)生菌改善因心力衰竭后大鼠紊亂的腸道細菌結構,促進腸道有益細菌的生長,進而改善心力衰竭 ?[42] 。補陽還五湯通過降低心力衰竭大鼠血清氧化三甲胺(TMAO)含量,改善腸道菌群,延緩心力衰竭進展 ?[43] ??傊?,基礎實驗研究在不同的動物心力 衰竭模型中驗證了中藥通過多靶點、多途徑發(fā)揮治療心力衰竭的作用,但心力衰竭具體證型的作用機制仍需進一步深入探討。
3 小結與展望
中醫(yī)藥治療心力衰竭的臨證療效頗佳,但仍面臨藥物成分繁雜、發(fā)揮作用的物質基礎不明確、基礎實驗機制的研究進展緩慢、系統(tǒng)的機制研究缺乏等問題,亟需開展高質量的研究。心力衰竭病機復雜,證型多樣,臟腑氣血陰陽之本虛,瘀血、痰濁、水飲、氣滯之標實,本虛標實之象缺乏切合的機制研究。各種局限性因素影響中醫(yī)治療心力衰竭研究的實際利弊結論,是中醫(yī)治療心力衰竭的薄弱環(huán)節(jié),制約了中醫(yī)治療心力衰竭的發(fā)展和推廣。盡管治療心力衰竭的中藥研究面臨著較大挑戰(zhàn),但借助于現(xiàn)代科學技術,在中醫(yī)理論指導下,進一步探討中藥治療心力衰竭的作用機制,深入挖掘中藥治療心力衰竭不同病機、證型的生物學內涵,系統(tǒng)闡明方藥及其有效組分的藥理機制,可能在心力衰竭治療研究中獲得新突破,展現(xiàn)中藥治療心力衰竭的綜合優(yōu)勢,從而加快推進有效方藥的應用和推廣,給予心力衰竭更好的治療支持。
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(收稿日期:2023.06.12)
(本文編輯 薛妮)