根據(jù)一項(xiàng)以人群為基礎(chǔ)的前瞻性隊(duì)列研究的結(jié)果,，慢性阻塞性肺病(COPD)與腦微出血(腦內(nèi)小血管疾病的一種標(biāo)志物)風(fēng)險(xiǎn)增高相關(guān),，而與年齡,、性別,、吸煙狀態(tài)和膽固醇水平等因素?zé)o關(guān),。
“抑郁癥,、體位不穩(wěn)定性、認(rèn)知和功能受損是已知的腦內(nèi)小血管疾病的后果,，同時(shí)也是COPD患者中常見的肺外表現(xiàn),，”比利時(shí)Ghent大學(xué)醫(yī)院的Lies Lahousse醫(yī)生及其同事說，“但尚不清楚COPD是否與腦內(nèi)小血管疾病的發(fā)生相關(guān),。”
該研究納入了參加鹿特丹掃描研究的165例COPD患者和645例非COPD患者,。鹿特丹掃描研究是一項(xiàng)以人群為基礎(chǔ)的隊(duì)列研究,，使用MRI評估年齡相關(guān)的腦變化,。
結(jié)果顯示，即使在校正年齡,、性別,、吸煙狀態(tài)、動脈粥樣硬化性大血管病變,、抗血栓劑的使用,、總膽固醇、甘油三酯和血清肌酐之后,，COPD患者的腦微出血患病率仍顯著高于肺功能正?；颊遊比值比(OR)，1.7,；95%置信區(qū)間(CI)：1.15~2.47,；P=0.007)。根據(jù)在線發(fā)表于7月19日的《美國呼吸與重癥醫(yī)學(xué)雜志》上的這篇文章的數(shù)據(jù),，COPD患者深部或小腦天幕下微出血的患病率也增加2倍以上(OR,，3.3；95%CI：1.97~5.53,；P＜0.001),。
對基線時(shí)無微出血的患者進(jìn)行的縱向分析顯示，在中位數(shù)為3.42年的時(shí)間段內(nèi),，COPD可獨(dú)立預(yù)測深部或小腦天幕下微出血風(fēng)險(xiǎn)增加6倍(OR,，7.1；95%CI：2.1~24.5,；P=0.002),。
“我們的結(jié)果與之前的兩項(xiàng)橫斷面研究一致，顯示COPD患者腦白質(zhì)病變體積顯著增加,，這是腦內(nèi)小血管疾病的另一標(biāo)志物,，并且已知與深部或小腦天幕下區(qū)域的微出血相關(guān),。”盡管COPD患者中微出血發(fā)生率增高與吸煙狀態(tài)無關(guān)，但研究者發(fā)現(xiàn),，在吸煙者中,，腦微出血的患病率顯著增高。既往研究顯示,，COPD患者動脈粥樣硬化性大血管病變患病率增高,，在這項(xiàng)分析中也考慮了這一因素。
研究者認(rèn)為,，鑒于腦微出血可能造成認(rèn)知和功能障礙,，該研究結(jié)果有助于識別易感患者人群，并提示有必要開展更多關(guān)于預(yù)防策略的研究,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Am J Respir Crit Care Med http://www.atsjournals.org/doi/abs/10.1164/rccm.201210-1884OC
The Role of Soluble Guanylyl Cyclase in Chronic Obstructive Pulmonary Disease
Constantinos Glynos, Lisa L Dupont, Theodoros Vassilakopoulos, Andreas Papapetropoulos, Peter Brouckaert, Athanassios Giannis, Guy F Joos, Ken R Bracke, and Guy G Brusselle
Rationale: Soluble guanylyl cyclase (sGC), a cyclic guanosine 5′-monophosphate (cGMP) generating enzyme, regulates smooth muscle tone and exerts anti-inflammatory effects in animal models of asthma and acute lung injury. In Chronic Obstructive Pulmonary Disease (COPD), primarily caused by cigarette smoke (CS), lung inflammation persists and smooth muscle tone remains elevated, despite ample amounts of nitric oxide (NO) that could activate sGC. Objective: To determine the expression and function of sGC in patients with COPD and in a murine model of COPD. Methods: Expression of sGCα1, α2 and β1 subunits was examined in lungs of never smokers, smokers without airflow limitation and patients with COPD; and in C57BL/6 mice after 3 days, 4 and 24 weeks of CS exposure. The functional role of sGC was investigated in vivo by measuring bronchial responsiveness to serotonin (5-HT) in mice using genetic and pharmacological approaches. Measurements and Main Results: Pulmonary expression of sGC, both at mRNA and protein level, was decreased in smokers without airflow limitation and in patients with COPD, and correlated with disease severity (FEV1%). In mice, exposure to CS reduced sGC, cGMP levels and protein kinase G activity. sGCα1-/- mice exposed to CS exhibited bronchial hyperresponsiveness (BHR) to serotonin. Activation of sGC by BAY 58-2667 restored the sGC signaling and attenuated BHR in CS-exposed mice. Conclusions: Downregulation of soluble guanylyl cyclase due to cigarette smoke exposure might contribute to airflow limitation in COPD.
