[Relation between level of expression of high mobility group protein B1 in hepatic tissue with the severity and prognosis of sepsis in rat].
OBJECTIVE
To investigate whether the levels of expression of high mobility group protein B1 (HMGB1) in hepatic tissue are related with severity and prognosis of sepsis in rat, in order to look for a dependable marker for monitoring and evaluating the efficiency of the treatment of sepsis.


METHODS
Ninety SD rats (specific-pathogen free, male, 250-300 g) were randomly divided into sham operation group (group A), cecal ligation and puncture (CLP) group (group B) and CLP followed by ethyl pyruvate (EP) treatment group (group C). Laparo fury was done aseptically, and the cecum was returned to the abdomen (group A) or CLP was carried out (group B and C). The abdominal wall was then closed layer by layer. Normal saline (NS) 2 ml (group A and B) or EP 2 ml (130 mg/kg, group C) was intraperitoneally injected and repeated every 12 hours. Five animals were sacrificed at 0, 6, 12, 24, 48 and 72 hours after the operation, blood samples and 100 grams of hepatic tissue were harvested before the animal died. Before sacrifice, activity, food taking, piloerection, diarrhea, anophthalmia, respiration, distention of intestine, hyperemia, ascites, and omental adhesion to the cecum, and hyperemia of lung were observed. Another group of 20 rats were used to observe the survival rate after CLP. The level of HMGB1 mRNA expression in the hepatic tissue was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), and the levels of interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in plasma were determined by enzyme linked immunoadsorbent assay (ELISA).


RESULTS
The mortality of sepsis was higher in group B than other groups (both P<0.01), that of group C was significantly lower than B but higher than A (both P<0.01). The levels of IL-1 beta, IL-6 and TNF-alpha in plasma rose to the peak at 6 hours after CLP in all groups, and group B>group C>group A (P<0.01), and they descended at 12 hours. The HMGB1 mRNA expression level in hepatic tissue was measurable at 6 hours and rose at 12 hours in group B, and maintained a high level up to 48 hours after CLP. The HMGB1 expression was positive correlated with IL-6 (r=0.91). The value in group C was significantly lower than group B at all time points (all P<0.01). The degree of severity and survival rate of sepsis were highly correlated with HMGB1 levels.


CONCLUSIONS
As a late-released inflammatory mediator, HMGB1 plays a key role in lethal effect of sepsis, the surviving time and the severity degree of sepsis are highly correlated with HMGB1 expression level in hepatic tissue.
Shao
Yi-ming
YM
Intensive Care Unit, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong, China. shaoyiming@sina.com
Yao
Hua-guo
HG
Liang
Xiao-zhong
XZ
Xia
Yan-huo
YH
D000818:Animals; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D024243:HMGB1 Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha