【摘要】 目的 探讨阿司匹林联合氯吡格雷双重抗血小板对脓毒症大鼠血小板功能和急性肺损伤（ALI）的影响。方法40只雄性Wistar大鼠随机分为对照组（N组）、内毒素组（LPS组）、阿司匹林组（A组）、氯吡格雷组（C组）、阿司匹林+氯吡格雷组（A+C组）,每组8只。N组、LPS组均给予生理盐水1 mL,A、C、A+C组则分别给予阿司匹林（100 mg/kg）、氯吡格雷（200 mg/kg）、阿司匹林（100 mg/kg）+氯吡格雷（200 mg/kg）灌胃3 d预处理,之后,除对照组外,余组均给予LPS 10 mg/kg腹腔注射造模。造模6 h后,取肺组织HE染色,光镜下观察各组大鼠肺组织病理,测定肺湿重/干重（W/D）比、PaO₂并计算PaO₂/FiO₂;用流式细胞仪测血小板CD62P和TLR4表达水平;采用ELISA法测血清TNF-α、IL-6浓度;用全血电阻法测血小板聚集率。结果 与N组比较,LPS组PaO₂、PaO₂/FiO₂显著下降,血小板聚集率、血小板CD62P和TLR4表达、肺W/D比及血清TNF-α、IL-6浓度均明显升高（均P<0.01）。与LPS组比较,A组、C组及A+C组血小板聚集率、血小板CD62P和TLR4表达、肺W/D比及血清TNF-α、IL-6浓度均有所降低,PaO₂、PaO₂/FiO₂回升（均P<0.05）,以A+C组效果最明显（均P<0.01）。光镜下,LPS组大鼠肺泡变形断裂、间隔增宽、大量炎症细胞浸润,而A组、C组、A+C组肺脏炎症程度较LPS组减轻,以A+C组减轻最明显。结论 阿司匹林联合氯吡格雷双重抗血小板比单一用药更能明显抑制TNF-α、IL-6的过度表达,下调血小板的活化聚集水平,从而减轻LPS诱导的ALI。更多还原

【Abstract】 Objective The present study aims to investigate the effect of aspirin and dual antiplatelet on platelet function in sepsis rats and acute lung injury.Methods Forty male Wistar rats were randomly divided into five groups（n = 8 each）:control group（N）,endotoxin group（LPS）,aspirin group（A）,clopidogrel group（C）,aspirin plus clopidogrel group（A +C）.The rats in N and LPS group were respectively treated with normal saline 1 mL while A,C and A + C group were respectively given aspirin（100 mg/kg）,clopidogrel（200 mg/kg）,aspirin（100 mg/kg） + clopidogrel（200 mg/kg） pretreatment by gavage for three days.Then,rats in tested groups were administered with LPS（10 mg/kg） through the intraperitoneal.Six hours after modeling,the histopathology of the lung was observed by light microscope,lung wet/dry weight ratio and PaO₂ were measured,PaO₂/FiO₂ was calculated,the expression level of platelet CD62 P and TLR4 were measured by flow cytometry instrument,the concentration of TNF-α and IL- 6 in serum were observed by ELISA,the rate of platelet aggregation was assayed by impedance platelet aggregometry.Results The level of PaO₂,PaO₂/FiO₂ decreased while the rate of platelet aggregation,the expression of platelet CD62 P and TLR4,lung W/D ratio,the concentration of TNF-α and IL- 6 were significantly increased in LPS group compared with N group（P < 0.01）.Platelet aggregation,the expression level of platelet CD62 P and TLR4,lung W/D ratio,the concentration of TNF-α and IL- 6 were significantly lower in intervention groups than those in LPS group,PaO₂,PaO₂/FiO₂ were improved（all P < 0.05）,the most obvious change occurred in dual antiplatelet group among intervention groups（P < 0.01）.Compared with N group,infiltration of inflammatory cell,interval widened,deformation and fracture of alveolar were found in LPS group,and treatment A or C or A + C could relieve lung injury.Conclusion LPS- induced ALI could be significantly alleviated by the dual antiplatelet of combination of aspirin and clopidogrel.Down- regulating of the expression of TNF-α,IL- 6 and inhibiting the excessive of platelet activation and aggregation maybe the mechanism.更多还原