High-molecular-weight hyaluronan--a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats.
High-molecular-weight hyaluronan--a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats.
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DOI：
10.1186/cc6982
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Quinn DA
中科院分区：
文献类型：
--
作者：
Liu YY;Lee CH;Dedaj R;Zhao H;Mrabat H;Sheidlin A;Syrkina O;Huang PM;Garg HG;Hales CA;Quinn DA
即使是中等大小的潮气量的机械通气也会协同增加脓毒症的肺损伤，并与促炎性低分子量透明质酸的产生有关。相比之下，高分子量透明质酸（HMW HA）被发现具有抗炎作用。我们假设HMW HA可以抑制脓毒症和机械通气相关的肺损伤。将Sprague-Dawley大鼠随机分为4组：不通气对照组;机械通气+脂多糖（LPS）输注组作为脓毒症模型;机械通气+LPS + HMW HA（1，600 kDa）预处理组;机械通气+LPS+低分子量透明质酸（35 kDa）预处理组。采用低潮气量（7 ml/kg）对大鼠进行机械通气。在机械通气前1小时输注LPS（1或3 mg/kg）或生理盐水。动物在研究前18小时通过腹膜内途径接受HMW HA或低分子量透明质酸，或在注射LPS后1小时静脉内接受HMW HA（0.025%、0.05%或0.1%）。通气4小时后，处死动物，测量肺中性粒细胞和单核细胞浸润、细胞因子产生和肺病理学评分。LPS诱导的肺中性粒细胞浸润、巨噬细胞炎性蛋白-2和TNFα mRNA和蛋白在1，600 kDa和35 kDa透明质酸预处理的存在下均降低。仅1，600 kDa透明质酸可完全阻断单核细胞和中性粒细胞浸润，并减轻肺损伤。当在LPS后1h静脉输注1，600 kDa透明质酸时，以剂量依赖性方式抑制肺中性粒细胞浸润、巨噬细胞炎性蛋白-2 mRNA表达和肺损伤。透明质酸的有益作用部分取决于化合物的正电荷。HMW HA可能被证明是机械通气脓毒症诱导的肺损伤的有效治疗策略。
Mechanical ventilation with even moderate-sized tidal volumes synergistically increases lung injury in sepsis and has been associated with proinflammatory low-molecular-weight hyaluronan production. High-molecular-weight hyaluronan (HMW HA), in contrast, has been found to be anti-inflammatory. We hypothesized that HMW HA would inhibit lung injury associated with sepsis and mechanical ventilation. Sprague–Dawley rats were randomly divided into four groups: nonventilated control rats; mechanical ventilation plus lipopolysaccharide (LPS) infusion as a model of sepsis; mechanical ventilation plus LPS with HMW HA (1,600 kDa) pretreatment; and mechanical ventilation plus LPS with low-molecular-weight hyaluronan (35 kDa) pretreatment. Rats were mechanically ventilated with low (7 ml/kg) tidal volumes. LPS (1 or 3 mg/kg) or normal saline was infused 1 hour prior to mechanical ventilation. Animals received HMW HA or low-molecular-weight hyaluronan via the intraperitoneal route 18 hours prior to the study or received HMW HA (0.025%, 0.05% or 0.1%) intravenously 1 hour after injection of LPS. After 4 hours of ventilation, animals were sacrificed and the lung neutrophil and monocyte infiltration, the cytokine production, and the lung pathology score were measured. LPS induced lung neutrophil infiltration, macrophage inflammatory protein-2 and TNFα mRNA and protein, which were decreased in the presence of both 1,600 kDa and 35 kDa hyaluronan pretreatment. Only 1,600 kDa hyaluronan completely blocked both monocyte and neutrophil infiltration and decreased the lung injury. When infused intravenously 1 hour after LPS, 1,600 kDa hyaluronan inhibited lung neutrophil infiltration, macrophage inflammatory protein-2 mRNA expression and lung injury in a dose-dependent manner. The beneficial effects of hyaluronan were partially dependent on the positive charge of the compound. HMW HA may prove to be an effective treatment strategy for sepsis-induced lung injury with mechanical ventilation.
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DOI：
10.1165/rcmb.2002-0167oc
发表时间：
2004-01-01
影响因子：
6.4
作者：
Mascarenhas, MM;Day, RM;Quinn, DA
通讯作者：
Quinn, DA
DOI：
10.1016/s0034-5687(00)00193-6
发表时间：
2001-01-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Hales, CA;Du, HK;Quinn, DA
通讯作者：
Quinn, DA
影响因子：
13.2
作者：
Breborowicz, A;Polubinska, A;Oreopoulos, D
通讯作者：
Oreopoulos, D
影响因子：
3.3
作者：
GOLDBLUM, SE;WU, KM;JAY, M
通讯作者：
JAY, M
影响因子：
8.8
作者：
BERG, S;JANSSON, I;WALTHER, S
通讯作者：
WALTHER, S