[Protective effect of protease inhibitor on renal function of rat challenged by lipopolysaccharide].
OBJECTIVE
To investigate the protective effects of protease inhibitor on lipopolysaccharide (LPS)-induced kidney injury in rats and its possible mechanism.


METHODS
Thirty-two male Wistar rats were divided into four groups randomly: normal control (n=6); LPS group (n=10), receiving intravenous endotoxin (LPS, O55:B5, 5 mg/kg); low-dose ulinastatin (UT) intervention group (n=8), receiving intraperitoneal UT 50 000 U/kg and LPS 5 mg/kg as above; high-dose UT intervention group (n=8), UT 100,000 U/kg and LPS 5 mg/kg. The following examinations were carried out: blood gas analysis, kidney pathological changes, plasma endothelin-1, plasma lactic acid, N-acetylglucosaminidase (NAG) in urine, and plasma creatinine (Cr) level.


RESULTS
Blood gas analysis showed that pH, partial pressure of oxygen in artery (PaO(2)) and base excess (BE) lowered significantly (all P<0.01) in LPS group compared with normal control group, and elevated in low-dose and large dose UT intervention groups compared with LPS group, the differences were statistically significant (P<0.01). The plasma endothelin-1 increased significantly (P<0.01) in LPS group compared with normal control group and intervention groups. Plasma lactate increased significantly in LPS group compared with normal control group (P<0.001), decreased significantly in intervention groups compared with LPS group (P<0.01). No significant difference was found between two intervention groups (P>0.05). Plasma Cr and urine NAG level increased in LPS groups, and the difference was significant compared with normal control groups and intervention groups (P<0.01). Pathohistologic examination revealed normal glomeruli but vacuolar degeneration of tubular epithelial cells, and part of them disrupted and desquamated, and also tubular dilatation. Only mild pathological changes were seen in the intervention groups. There was no obvious difference in morphology between two intervention groups.


CONCLUSIONS
The protease inhibitor, UT, may alleviate LPS-induced inflammatory reaction and damage to kidney in rats.
Wang
Bo
B
Department of Emergency, The First Affiliated Hospital, Peking University, Beijing 100034, China. bjwbdoctor@hotmail.com
Chen
Xu-yan
XY
Xiong
Hui
H
Li
Xiu-qing
XQ
Tian
Ya-nan
YN
Gao
Yu-song
YS
Liu
Xin-min
XM
D000818:Animals; D004195:Disease Models, Animal; D004347:Drug Interactions; D006023:Glycoproteins / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D006023:Glycoproteins; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; C028665:urinastatin