Protective Effects Of Quercetin In Rats With Lipopolysaccharide- Induced Acute Lung Injury

Acute respiratory distress syndrome is a clinical emergency characterized by persistent hypoxemia, with a high morbidity and mortality. Acute lung injury is the fundermental pathological changes of ARDS. The pathogenesis of the disorder is very complicated and still riddled. In clinic, there is no effective treatment method. Now people are aware that ALI/ARDS are kinds of systemic disorders start-uped by many risk-factors involving many celluar factors and inflammatory cells. Inflammatory reaction play the critical roles in this process, so it is probably a effective method to treat ALI by inhibitting inflammatory damage. Quercetin is a flavonoid molecule ubiquitous in nature and functions as an anti-inflammatory, anti-oxidant, anti-adhesive agent with little toxicity in vivo and in vitro. It had been reported to improve the survival rate of endotoxin-induced shock rats. whether it has protective effect on ALI and its probable mechanisms have not yet reported. Objective To investigate the protective effects of quercetin in rats with lipopolysaccharide-induced acute lung injury(ALI). Method lipopolysaccharide(LPS, 6mg/kg, iv)reproduced the model of ALI in rats. 24 SD rats were randomly divided into three group: control group,LPS group,Quercetin pretreatment group。Six hours after lipopolysaccharide or normal saline was administered by intravenous injection, the levels of the tumor necrosis factor-alpha(TNF-a),interleukin-8 (IL-8) and P-selectin in serum (or plasma) were measured by radioimmunoassay and arterial blood gases were analysed. The rats were sacrificed by bleeding at the end of experiment, the pathological changes of rat's lung were observed, the wet and drought ratio(W/D) of the lung and the quantity of PMN in bronchoalveolar lavage fluid(BALF) were calculated, the concentration of lung myeloperoxidase(MPO) was detected by the method of colorimetry. The levels of TNF-a, IL-8and P-selectin of lung tissue were measured by radioimmunoassay. Here are the results:1 The effect of quercetin on PaO2 of ALI induced by LPS Compared with the control group(14.26±1.05kPa), PaO2 of LPS group(9.75±0.86kPa)decreased significantly(P＜0.01). Compared with LPS group , however, PaO2 of quercetin pretreatment group(13.15±0.58 kPa)increased obviously(P＜0.01).2 The effect of quercetin on W/D,MPO,and the quantity of PMN in BALF of ALI induced by LPSCompared with control group ( 4.08±0.30,0.52±0.02,3.10±0.5),the W/D,MPO, and the quantity of PMN in BALF in LPS group(5.65±0.56,2.58±0.35, 9.24±0.56) were increased significantly(P＜0.01). Compared with LPS group , however, the W/D,MPO, and the quantity of PMN in BALF in quercetin pretreatment group(4.90±0.31,1.29±0. 39,7.5±0.72) declined obviously(P＜0.05).3 The effect of quercetin on TNF-a,IL-8,P-selectin of ALI induced by LPSCompared with control group(4.14±0.86 ng/ml,15.04±6.82 ng/ml),the levels of TNF-a in serum and lung tissue of LPS group(6.13±0.44 ng/ml,54.37±16.99ng/ml)increased significantly(P＜0.01). Compared with LPS group , however, the levels of TNF-a of quercetin pretreatment group(4.84±0.51ng/ml,20.53±6.83ng/ml)reduced obviously(P＜0.01). Compared with control group(89.5±16.13 pg/ml,69.71±10.67 pg/ml),the levels of IL-8 in serum and lung tissue of LPS group (1272.2±140.09 pg/ml,179.00±25.38 pg/ml)increased significantly(P＜0.01). Compared with LPS group , however, the levels of IL-8 of quercetin pretreatment group(4.84±0.51ng/ml,20.53±6.83ng/ml)declined obviously(P＜0.01). Compared with control group(2.13±0.29 ng/ml,4.62±0.99ng/ml),the levels of P-selectin in plasma and lung tissue of LPS group(5.34±0.41 ng/ml,15.43±2.18ng/ml)increased significantly, (P＜0.01). Compared with LPS group , however, the levels of P-selectin of quercetin pretreatment group(3.53±0.41ng/ml,7.97±1.27ng/ml)decreased obviously(P＜0.01).4 The effect of quercetin on the pathological change of rats, lungIt can be seen alveolar septa thickening, alveol...