卡巴胆碱对大鼠脓毒症所致肝功能损害的保护作用

Protective effect of carbachol against abdominal sepsis-induced liver dysfunction in rats

目的:研究卡巴胆碱对脓毒症大鼠促炎症因子所致肝损伤的保护作用。方法:雄性SD大鼠32只,采用盲肠结扎穿孔术(CLP)制备大鼠脓毒症模型。随机分为CLP组和卡巴胆碱干预组(CAR组),每组16只,CLP后立即静脉注射CAR 10μg/kg(CAR组)或等量生理盐水(CLP组)。于CLP后6h和12h取血检测血浆丙氨酸转氨酶(ALT)活性,然后处死取肝组织,检测肿瘤坏死因子-α(TNF-α)和一氧化氮(NO)含量、髓过氧化物酶(MPO)活性以及肝组织含水率。结果:CAR组肝组织TNF-α含量显著低于CLP组,CLP后6 h[(358.15±82.55)Pg/g比(536.12±104.25)Pg/g]和12h[(500.85±122.53)pg/g比(740.50±133.47)pg/g]差异非常显著(P<0.05);NO和MPO水平也显著低于CLP组(P<0.05)。CLP后6h CAR组与CLP组血浆ALT活性[(48.6±3.0)U/L vs.(55.3±4.0)U/L]和组织含水率[(70.9±2.9)%vs.(75.2-±-2.2)%]比较,差异均有统计学意义(P<0.05)。结论:卡巴胆碱对大鼠腹腔脓毒症引起的肝功能损害有明显保护作用,其机制可能与其抑制肝脏TNF-α和NO水平、降低MPO活性,减轻肝组织炎症和水肿有关。

Objective：To investigate the effect of carbaehol （CAR） in protecting the liver against injury due to pro-inflammatory eytokines in sepsis in rat. Methods：Thirty-two Sprague-Dawley rats were subjected to cecal ligation and puncture （CLP） to produce sepsis,and they were randomly divided into two equal groups： sepsis model group （CLP group,n： 16）and sepsis with CAR-treatment group （CAR group,n= 16）. Carbachol （10 μg/kg, CAR group） or normal saline （CLP group） was immediately injected via the penile vein. The animals were sacrificed at 6 hours and 12 hours after CLP, and specimens of liver were harvested for evaluation of tumour necrosis factor-α （TNF-α）, nitric oxide （NO） and myeloperoxidase （MPO）, and assessment of the rate of water content （ratio of dry to wet weight）. The plasma activity of alanine aminotransferase （ALT） was also detected. Results： The levels of TNF-α in CAR group were （358.15±82. 55）pg/g and （500.85±122.53）pg/g at 6 hours and 12 hours, respectively,after CLP, they were all significantly lower than those of the CLP group[（536.12 ±104. 25） pg/g and （740. 50 ± 133.47）pg/g, respectively, P〈0. 05]. The levels of NO and MPO in CAR group were also greatly decreased compared with those of CLP group（P〈0. 05）. The activity of ALT and the rate of tissue water content of CAR group in liver were （48. 6±3.0） U/L and （70. 9±2.9）% at 6 hours, respectively,after CLP, they were all significantly lower than those of the CLP group [（55.3±4.0） U/L and （75.2±2.2）%, respectively,P〈0.05]. Conclusion： The results indicate that CAR plays a protective role in sepsis-induced hepatic injury by inhibiting the production of TNF-α, NO and MPO. It also alleviate inflammation and edema of jejunal mucosa.