甲壳质酶样蛋白在哮喘患者肺及循环中含量
2008/06/06
进化过程中保守的18糖基水解酶家族包含了甲壳质酶及其类似物－甲壳质酶样蛋白，但其缺乏蛋白活性。哺乳动物的酸性甲壳质酶最近被证实和模型动物哮喘相关。和甲壳质酶相似的甲壳质酶样蛋白YKL-40容易在血清中检出，但与哮喘发病的关系还不明确。作者检测了3个队列哮喘人群YKL-40水平。
结果显示哮喘患者血清YKL-40水平与对照组比较明显增加。血清YKL-40水平与患者病情正相关，与患者FEV1负相关。高水平YKL-40患者使用急救吸入剂频率、口服糖皮质激素剂量及住院天数较低YKL-40患者明显增加。一组人群肺内YKL-40水平与血清YKL-40水平进行了比较，两者明显相关，肺内YKL-40水平与气道重塑亦相关。因此作者人为YKL-40在哮喘发作中有主要作用。
结果显示哮喘患者血清YKL-40水平与对照组比较明显增加。血清YKL-40水平与患者病情正相关，与患者FEV1负相关。高水平YKL-40患者使用急救吸入剂频率、口服糖皮质激素剂量及住院天数较低YKL-40患者明显增加。一组人群肺内YKL-40水平与血清YKL-40水平进行了比较，两者明显相关，肺内YKL-40水平与气道重塑亦相关。因此作者人为YKL-40在哮喘发作中有主要作用。
（刘颖格 第四军医大学西京医院呼吸内科 710032 摘译)
(N Engl J Med 2007;357:2016-2027)
(N Engl J Med 2007;357:2016-2027)
A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma
ABSTRACT
Background The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3–like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.
Methods We quantified serum YKL-40 levels in three cohorts of patients with asthma — one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin — as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.
Results Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.
Conclusions YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.
N Engl J Med 2007;357:2016-27.
Copyright © 2007 Massachusetts Medical Society.
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长期使用β受体阻滞剂减轻小鼠哮喘模型气道炎症和粘蛋白含量
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哮喘患者血浆磷脂酶A2的活性与体重指数及血浆胆固醇浓度相关性分析
