胍丁胺对酵母多糖诱导急性肺损伤的器官保护作用

目的 探讨胍丁胺(AGM)对酵母多糖(ZYM)诱导小鼠全身炎症反应和急性肺损伤(ALI)时器官的保护作用.方法 将32只成年雄性C57BL/6小鼠按随机数字表法分为正常对照组磷酸盐缓冲液(PBS)0.5 ml]、AGM对照组(AGM 200 mg/kg)、模型组(ZYM 500 mg/kg+ PBS 0.5 ml)、AGM治疗组(ZYM 500 mg/kg+AGM 200 mg/kg)4组,每组8只.AGM、ZYM、PBS为腹腔注射.于给药12h后采用酶联免疫吸附法(ELISA)测定血清和腹腔渗出液中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及一氧化氮(NO)含量;同时测定肺组织中TNF-α、IL-6、髓过氧化物酶(MPO)活性和核转录因子-kB p65(NF-kB p65)的DNA结合活性,并观察肺组织病理改变.结果 ZYM注射后12 h小鼠精神萎靡、活动减少、饮水减少;而AGM治疗组小鼠精神状况、活动、饮水均好转.AGM治疗能降低ZYM诱导的血清及腹腔渗出液的TNF-α(ng/L:252.6±32.1比421.7±76.7,295.7±78.6比592.0±84.3,均P＜0.05)、IL-6(ng/L:2 198.8±281.8比4 725.3±615.4,19 829.3±3 647.0比47 751.3±5 264.8,均P＜0.05)和NO (μmol/L:33.2±4.3比50.2±5.2,14.0±3.6比45.4±5.2,均P＜0.05)水平升高;AGM治疗也能够抑制ZYM引起的肺组织TNF-α(ng/L:245.7±39.1比378.3±67.6,P＜0.05)、IL-6 (ng/L:810.3±175.6比1 172.4±203.3,P＜0.05)、MPO活性(ng/mg:24.9±4.4比37.3±5.8,P＜0.05)和NF-kB p65(吸光度值:0.272±0.029比0.347±0.037,P＜0.05)升高.正常对照组和AGM对照组间各指标无明显差异.ZYM可导致肺组织出现严重的炎症改变,包括血管扩张、中性粒细胞浸润;AGM治疗后肺组织损伤明显减轻.结论 AGM能够缓解ZYM诱导的小鼠全身炎症反应和ALI的严重程度.

The protective effects of agmatine in zymosan induced acute lung injury in mice

Objective To examine the protective effects of agmatine (AGM) adminstration on zymosan (ZYM)-induced inflammatory reponse and acute lung injury (ALI) in mice.Methods 32 adult male C57BL/6 mice were randomly divided into four groups (n=8 each) to receive i.p.administration of:① phosphate buffer saline (PBS,0.5 ml); ②AGM (200 mg/kg); ③ZYM (500 mg/kg)+PBS (0.5 ml),and ④ AGM (200 mg/kg)+ZYM (500 mg/kg).Blood samples and peritoneal exudates were collected from the animals 12 hours after drug administration for concentration of tumor necrosis factor-a (TNF-a),interleukin-6 (IL-6) and nitric oxide (NO) by enzyme linked immunosorbent assay (ELISA).Lung tissue samples were also collected at the same time for histological examination,and determination of tissue content of TNF-α,IL-6,myelopcroxidase (MPO) activity and nuclear factor-kB p65 (NF-kB p65) DNA-binding activity.Results 12 hours after ZYM injection,the treated mice became lethargic,their activity and water consumption were both reduced,AGM greatly improved the general status,activity,and water consumption in treated mice,while attenuated the increase of TNF-α (ng/L:252.6±32.1 vs.421.7±76.7,295.7±78.6 vs.592.0±84.3,both P＜0.05),IL-6 (ng/L:2 198.8±281.8 vs.4 725.3±615.4,19 829.3±3 647.0 vs.47 751.3±5 264.8,both P＜0.05) and NO (μmol/L:33.2±4.3 vs.50.2±5.2,14.0±3.6 vs.45.4± 5.2,both P＜0.05) in serum and peritoneal exudates caused by ZYM.AGM also attenuated the increase of TNF-a (ng/L:245.7±39.1 vs.378.3±67.6,P＜0.05),IL-6 (ng/L:810.3±175.6 vs.1 172.4±203.3,P＜0.05),MPO activity (ng/mg:24.9±4.4 vs.37.3±5.8,P＜0.05) and NF-kB p65 optical density (absorbance value:0.272 ± 0.029 vs.0.347 ± 0.037,P＜ 0.05) in the lung tissue seen in ZYM treated animals.There was no significant difference between normal PBS and AGM treated group in all the indexes examined.Histological examination demonstrated that ZYM treated animals had severe inflammatory reaction in lung tissues (manifested as vasodilatation and neurophils infiltration) and AGM significantly reduced such injury.Conclusion AGM can attenuate the ALl and inflammation induced by ZYM in mice.