羟乙基淀粉130/0.4对内毒素致大鼠急性肺损伤时TLR4表达的影响

目的 探讨羟乙基淀粉130/0.4对内毒素致大鼠急性肺损伤(ALI)时Toll样受体4(TLR4)表达的影响.方法 雄性SD大鼠30只,体重250～300 g,随机分为5组(n=6),生理盐水对照组(NS组)、ALI组和H_(1-3)组.ALI组、H_1组和H_2组经右颈内静脉注射内毒素10ms/kg制备大鼠ALI模型,H_1组和H_2组注射内毒素完毕1 min后,右颈内静脉分别输注6%羟乙基淀粉130/0.4 15和30ml/kg,H_3组仅右颈内静脉输注6%羟乙基淀粉130/0.4 30 ml/kg,速率均为0.2 ml/min.注射内毒素后6 h时处死大鼠取肺,光镜下观察肺组织病理学;采用RT-PCR检测TLR4 mRNA的表达水平,Western bloting法检测肺组织TLR4蛋白的表达水平.结果 与NS组相比,ALI组TLR4 mRNA和蛋白的表达上调(P＜0.05),H_3组差异无统计学意义(P＞0.05);与ALI组相比,H_1组和H_2组TLR4 mRNA和蛋白的表达下调(P＜0.05);H_1组和H_2组TLR4 mRNA和蛋白的表达比较差异无统计学意义(P＞0.05).病理结果显示:H_1组和H_2组肺损伤程度较ALI组明显减轻.结论 羟乙基淀粉130/0.4可能通过抑制TLR4表达上调,减轻炎性反应,从而减轻内毒素致大鼠ALI.

Effect of hydroxyethyl starch on TLR4 expression in the lung tissue in a rat model of acute lung injury

Objective To investigate the effect of hydrexyethyl starch(HES)130/0.4 on Toll-like receptor 4(TLR4)mRNA and protein expression in the lung tissue in a rat model of acute lung injury(ALI)induced by lipopolysaccharide(LPS).Methods Thirty pathogen-free male SD rats weighing 250-300 g were randomly divided into5 groups(n=6 each): group Ⅰ normal control(group C);group Ⅱ ALI;group Ⅲ andⅣ HES 15 ml/kg or 30 ml/kg+ALI and group Ⅴ HES 30 ml/kg.The animals were anesthetized with intraperitoneal 10% chloral hydrate 300 mg/kg.The right internal jugular vein was cannulated for fluid and drug administration.ALI was induced by LPS 10 mg/kg iv in group Ⅱ,Ⅲ and Ⅳ.HES 130/0.4 was infused iv at0.2 ml/min at 1 min after LPS administration in group Ⅲ,Ⅳ and Ⅴ.The animals were killed at 6 h after IP LPS and the lungs were immediately removed for microscopic examination and detection of TLR4 mRNA and protein expression by RT-PCR and Western blotting.Results The TLR4 mRNA and protein expression was significantly higher in LPS group than in group C.HES 130/0.4 15 and 30 ml/kg significantly reduced the LPS-induced increase in TLR4 mRNA and protein expression in the lung tissue.There was no significant difference in TLR4mRNA and protein expression between the two ALI+HES groups(Ⅲ,Ⅳ).Conclusion HES 130/0.4 can inhibit ALI-induced ALI by depressing the TLR4 expression in the lung.