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2020年4月15日，心血管頂級雜志Circulation在線發表了武漢大學李紅良教授與加拿大渥太華大學心臟中心的PeterP. Liu教授合作的題為“The Science underlying COVID-19: Implications for the Cardiovascular System”的深度綜述文章。該文章圍繞COVID-19對心血管系統的影響，從臨床和基礎的角度對COVID-19進行了系統地梳理和闡述。現有的流行病學資料表明，COVID-19患者中合并心血管疾病的比例較高，而該類患者的死亡率也顯著上升。據報道，合并心血管疾病的COVID-19患者死亡率為10.5%，合并高血壓患者的死亡率為6.0%，遠遠高于沒有合并癥的患者（0.9%）。細胞表面受體ACE2和絲氨酸蛋白酶TMPRSS2是SARS-CoV-2入侵宿主細胞的關鍵蛋白。ACE2和TMPRSS2共同表達于肺臟，心臟，胃腸道，肝臟，腎臟，神經元以及免疫細胞。研究表明，在糖尿病，高血壓以及心衰患者中ACE2的表達量和活性顯著增高。另外，ACE2的表達水平具有明顯的性別差異，即男性患者的死亡率高于女性。在心衰患者中，男性外周循環的ACE2明顯高于女性。ACE2能夠將AngII水解成Ang 1-7，后者作用于Mas受體，發揮拮抗Ang II/AT1R的效應，如降低血壓，舒張血管，抑制炎癥和氧化應激等。SARS-CoV-2的感染引起ACE2的降低，使RAS系統的平衡向AngII/AT1R偏移，促進組織損傷。盡管目前并沒有確切的證據評估，RAS系統抑制劑，如ACEIs/ARBs類藥物對COVID-19患者的利弊，多數醫療組織推薦具有ACEIs/ARBs用藥指征的患者繼續使用該類藥物。事實上，本團隊的大樣本臨床研究證實，對于有用藥指征的COVID-19患者（如高血壓），ACEIs/ARBs的使用益處大于風險。 
血管平滑肌細胞上表達ACE2和TMPRSS2，也是新冠病毒的潛在感染靶點。COVID-19患者的病理分析結果發現，在肺臟和其它受累組織中均存在微血管炎癥和微血栓形成。此外，巨噬細胞的活化和內皮細胞的功能失調也對微血管炎癥和微血栓形成起著推波助瀾的作用。微血管炎癥和微血栓形成能夠加重患者的缺氧狀態，促進組織損傷，嚴重影響患者預后。針對合并微血管炎癥和微血栓形成的患者，如實驗室檢查發現IL-6和D-二聚體顯著升高，應盡早考慮抗炎和抗凝藥物的治療，改善患者預后。8-28%的COVID-19患者伴有肌鈣蛋白的升高，提示心肌損傷的發生。合并心肌損傷的COVID-19患者，死亡率顯著上升，表明心肌損傷和患者的預后密切相關。部分患者可能伴有心臟的直接受累，包括心肌病、心肌炎或心力衰竭，影響患者的總體預后，早期識別和干預能夠顯著改善患者的臨床結局。疑似急性心肌炎和心肌病的患者，心臟磁共振成像檢查具有一定的價值。對于合并心衰的患者，應該考慮應用包括RAS抑制劑在內的相關治療藥物。心律失常是COVID-19患者的另一種常見并發癥。研究表明，ICU收治的COVID-19患者中，房顫發生率高達50%，這些患者也伴有室性心律失常和心臟驟停。COVID-19患者心律失常的高發生率可部分歸因于患者在病毒感染時的代謝紊亂、缺氧、神經激素及炎癥應激，也可能與潛在的心肌炎和治療藥物的副作用有關。DOI:10.1161/CIRCULATIONAHA.120.047549 
Corona Virus Disease 2019 (COVID-19) pandemic has impacted health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with pre-existing cardiovascular (CV) disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of the SARS-CoV-2 virus is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S spike protein. The continued viral shedding in the asymptomatic and pre-symptomatic individuals enhances its community transmission. The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease. The tissue localization of the receptors correlates with COVDI-19 presenting symptoms and organ dysfunction. Virus-induced ACE2 down regulation may attenuate its function, diminish its anti-inflammatory role, and heightened angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4 and some CD8 T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyper stimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation, and balanced immune response. Persistent immune activation in predisposed patients, such as the elderly and those with CV risk, can lead to hemophagocytosis like syndrome, with uncontrolled amplification of cytokine production, leading to multi-organ failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, particularly in those showing continued rise, along with cytokines such as IL-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome and thrombosis remain important. Specific evidence based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history.機構簡介武漢大學動物實驗中心（簡稱中心）和武漢大學ABSL-Ⅲ實驗室（生物安全三級動物實驗室，簡稱A3實驗室）源于1958年成立的湖北醫學院動物室，迄今已走過甲子芳華。1994年，湖北醫科大學動物實驗中心成立，后于2000年并入武漢大學，實驗動物中心由此劃歸武漢大學醫學院；2003年，武漢大學動物實驗中心與武漢大學ABSL-Ⅲ實驗室由國家發展與改革委員會、教育部、武漢大學共同投資建設而成；2012年，武漢大學模式動物協同創新中心成立，繼而成立武漢大學模式動物研究所，和中心/A3實驗室同為武漢大學二級單位，實行一套班子，三塊牌子，是面向校內外開放的公共服務平臺和科研機構。編輯、審核：蘇果 薦稿：Yin Yuan 素材來源：武漢大學動物實驗中心（簡稱中心）、武漢大學ABSL-Ⅲ實驗室、期刊Circulation 網址鏈接：https://www./doi/abs/10.1161/CIRCULATIONAHA.120.047549 版權聲明：文章轉摘只為學術傳播，如涉及侵權問題，請聯系我們，我們將及時修改或刪除。 |
