Protective effect of recombinant human brain natriuretic peptide on acute renal injury induced by endotoxin in canines / 中国生化药物杂志

ABSTRACT

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 groupsblank 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), 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 decreased in high-dose intervention group at 2 h and 4 h (P<0.01).Compared with low-dose intervention group at the same point,SVRI in high-dose intervention group were significantly decreased at 4 h (P<0.05 ).Compared with control group at the same point,the expressions of high mobility group box 1 protein (HMGB-1)in blood serum in low- and high-dose intervention groups were significantly decreased(P<0.01);Compared with low-dose intervention group at the same point,the expressions of HMGB-1 in blood serum in high-dose intervention group were significantly decreased (P<0.05).Conclusion rhBNP can effectively reduce canine kidney tissue injury mediated by endotoxin and improve kidney function,reduce SVRI,and its therapeutic effect of rhBNP was in a dose-response relationship.rhBNP can effectively reduce HMGB-1 levels in blood serum of sepsis shock canines,which may be associated with the decrease of late inflammatory factor HMGB1.