rhBNP对内毒素介导的犬急性肾损伤的保护作用  

Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines

作　　者：李牧[1] 刘岩[2] 李辉 

机构地区：[1]沈阳医学院附属中心医院普外一科,辽宁沈阳110024 [2]沈阳医学院附属中心医院骨外二科,辽宁沈阳110024 [3]中国解放军第八十九医院肾内科,山东潍坊261021

出　　处：《中国生化药物杂志》2014年第3期43-47,51,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：山东省教育厅课题资助(J11LF66)

摘　　要：目的：观察重组人脑利钠肽（recombinant human brain natriuretic peptide，rhBNP）对犬急性肾损伤的保护作用，探讨rhBNP对内毒素介导的犬急性肾损伤血清HMGB1水平的影响。方法20只健康成年犬随机均分为4组（n＝5）：空白对照组，脓毒症组、低剂量干预组和高剂量干预组。除空白组外的15只健康成年犬静脉注射脂多糖建立脓毒症休克模型。脓毒症组和空白组不给予rhBNP处理，低剂量干预组和高剂量干预组分别给予5μg/kg、10μg/kg rhBNP处理。观察各组犬于0、2、4、8、12 h时的外周血管阻力（systemic vascular resistance index，SVRI），并在以上各时间点留取适量外周静脉血用于检测血清高迁移率族蛋白-1（high mobility group box-1，HMGB-1）的水平和肌酐值（creatinine values，CR），于12 h后处死动物并留取肾脏标本用于组织病理学观察。结果①光镜下观察脓毒症组肾小管上皮细胞肿胀、出现管型，间质细胞肿胀，肾脏组织病理评分为3分；低剂量干预组与高剂量干预组上述改变明显减轻，但2者镜下观察差异不显著，肾脏组织病理评分均为1～2分。②与同时间点脓毒症组相比，低剂量干预组在8、12 h时血清CR水平显著降低（P＜0.01），高剂量干预组血清CR水平在4 h、8 h、12 h时显著降低（P＜0.01）；高剂量干预组与低剂量干预组相比，血清CR水平在4 h、8 h、12 h时均有显著性差异（P＜0.05）。③与同时间点脓毒症组比较，低剂量干预组在2 h时SVRI显著降低（P＜0.01），高剂量干预组在2 h、4 h时SVRI显著降低（P＜0.01）；高剂量干预组与低剂量干预组相比，SVRI于4 h时差异有统计学意义（P＜0.05）。④与同时间点脓毒症组相比，低剂量干预组与高剂量干预组犬血清HMGB-1水平均显著降低（P＜0.01）；高剂量干预组与同时间点低剂量干预组比较，血清HMGB-1水平显著性减少（P＜0.05）。结论 Objective To observe the influence of recombinant human brain natriuretic peptide(rhBNP)on serum HMGB1 levels in canines''acute renal injury induced by endotoxin and explore its protective role of rhBNP in protecting canines''kidney against acute renal injury.Methods A total of 20 healthy dogs were randomly divided into four groups:blank group,sepsis shock group,low-dose intervention group and high dose intervention group, and there were 5 rats in each group.After establishing the model of canines''sepsis shock induced by endotoxin,15 canines (besides blank group)were randomly divided into 3 groups.As follows,5 μg/kg rhBNP was given to the low-dose intervention group,10μg/kg rhBNP was given to the high-dose intervention group.But nothing was given to control group.Systemic vascular resistance index(SVRI)at 0 h,2 h,4 h,8 h,12 h were observed by PICCO instrument.High mobility group box 1 protein (HMGB-1)and creatinine(CR)in blood samples at each time point were detected.After 12 hours,kidney samples were taken for histological examination.Results The results revealed that some renal tubulars epithelial cell were swelled,some epithelial cells were atrophy and interstitial cells swelled in control group under the light microscope.Kidney pathology score was 2-3.But these changes were improved in low-and high-dose intervention groups,and there were no significant difference in the latter two groups,kidney of both groups pathology score were 1-2.Compared with control group at the same point,CR of blood serum were significantly decreased in low-dose intervention group at 8 h,12 h(P<0.01),&nbsp;and high-dose intervention group significantly decreased at 4 h,8 h,12 h(P<0.01).Compared with low-dose intervention group at the same point,CR of blood serum in high-dose intervention group were significantly decreased at 4 h,8 h,12 h (P<0.05).Compared with control group at the same point, systemic vascular resistance index(SVRI)were significantly decreased in low-dose intervention group at 2 h (P<0.01 ),but significantly decrea

关 键 词：脓毒症 急性肾损伤 重组人脑利钠肽 高迁移率族蛋白 

分 类 号：R34[医药卫生—基础医学]