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甲基泼尼松龙对外科型慢加急性大鼠肝衰竭的作用

The role of methylprednisolone on surgical acute-on-chronic liver failure on rats
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摘要 目的 观察糖皮质激素甲基泼尼松龙(简称甲强龙)对外科型慢加急性大鼠肝衰竭的治疗作用.方法 在大鼠胆总管双重结扎梗阻性黄疸14 d模型的基础上进行下一步造模,第2次手术为胆十二指肠内引流、肝缺血再灌注30 min、30%肝部分切除,并经门静脉及尾静脉注射甲强龙,术后6h检测大鼠的肝功能、细胞因子水平、肝组织病理学特点和肝细胞超微结构,并观察24 h生存率.结果 对照组大鼠丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBIL)值及肿瘤坏死因子-α(TNF-α)、干扰素γ(IFN-γ)水平分别为(2436.5±518.1)、(3519.1±414.6)、(156.3 ±33.7) U/L;(419.6±162.1)、(581.3±178.1) ng/L,肝组织病理和电镜超微结构表明符合肝衰竭特点.与对照组比较,分别尾静脉和门静脉注射甲强龙均可以显著提高肝衰竭动物的24 h生存率,显著降低其ALT、AST、TBIL水平,降低TNF-α、IFN-γ,减轻肝脏组织病理损伤和肝细胞线粒体的肿胀程度,并且经门静脉注射明显优于经尾静脉注射(P<0.05).结论 甲强龙对外科型慢加急性肝衰具有保护治疗作用,且经门静脉给药效果最佳. Objective To investigate the effects of methylprednisolone in rats with acute-on-chronic liver failure.Methods An obstructive jaundice model with double bile duct ligation in rats was established firstly.Three groups (7,14,21 d) were set according to the days of obstruction.The second operation includes choledochojejunostomy,ischemia-reperfusion and hepatectomy.Three groups (15,30,45 min) were set according to the time of ischemia.The mastoid lobe and quadrate lobe of liver were resected,which occupied 30% of the total volume.After 6 hours of modeling,the serum liver function,tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ) activity were determined,histopathologic features of liver tissue and hepatocyte ultra-structure were evaluated under light microscope and electronscope,respectively.In another set of experiments,rats were monitored for a 24-hour observation period to investigate their survival rate.Results In Control group rats,the levels of alanine aminotransferase,aspartate aminotransferase,total bilirubin,TNF-α,IFN-γ were (2 436.5 ± 518.1),(3 519.1 ± 414.6),(156.3 ± 33.7) U/L; (419.6 ± 162.1),(581.3 ± 178.1) ng/L,respectively.Histopathology and ultrastructure show good compliance with the characteristics of liver failure.Compared with control group,the levels of liver function,activity of inflammatory cytokines,liver pathologic damage and swelling rates of liver mitochondria were significantly alleviated both in the tail vein and portal vein injection of methylprednisolone group (P 〈 0.05).Conclusion Methylprednisolone may play protective and therapeutic role for acute-onchronic liver failure,and the effect may be better administered via the portal vein.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2014年第10期2135-2137,共3页 Chinese Journal of Experimental Surgery
基金 湖北省科技厅基金资助项目(2010CDB06807)
关键词 慢加急性肝衰竭 梗阻性黄疸 甲基强的松龙 炎性细胞因子 Acute-on-chronic liver failure Obstructive jaundice Methylprednisolone Inflammatory cytokines
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