[Effect of high volume hemofiltration on expression of Toll-like receptor 4 in myocardium in endotoxin induced shock in dogs].
OBJECTIVE
To investigate the effects of high volume hemofiltration (HVHF) on the expression of Toll-like receptor 4 (TLR4) mRNA in myocardium in endotoxin (lipopolysaccharide, LPS) induced shock in dogs.


METHODS
Sixteen healthy male dogs were injected with LPS 650 microg/kg via central vein to reproduce the model of endotoxin shock. All dogs were divided randomly into two groups: control group and therapy group, with 8 dogs in each group. Contents of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-10 in circulation were measured by radioimmunological method. The expression levels of TLR4 mRNA in all group were measured by reverse transcription-polymerase chain reaction (RT-PCR). Change in myocardial histopathology was observed and analyzed with the aid of electron microscope.


RESULTS
The contents of TNF-alpha (microg/L: 0.59+/-0.15, 0.51+/-0.12, 0.41+/-0.10), IL-6 (ng/L: 11.08+/-2.83, 9.82+/-2.58, 8.25+/-2.05), IL-10 (microg/L: 57.28+/-5.93, 53.81+/-5.83, 50.67+/-6.33) in therapy group were found to have decreased significantly at 1, 2, and 4 hours after HVHF compared with those when the model was completed [(0.84+/-0.16) microg/L, (16.97+/-2.50) ng/L, (70.86+/-5.43) microg/L], showing a continuous trend of lowering (all P<0.01). The contents of TNF-alpha, IL-6, IL-10 in therapy group were lower than those in control group significantly at any time point [TNF-alpha (microg/L): 0.75+/-0.14, 0.74+/-0.11, 0.72+/-0.11, IL-6 (ng/L): 15.33+/-3.20, 14.66+/-3.24, 14.20+/-3.33, IL-10 (microg/L): 71.54+/-4.73, 70.71+/-4.34, 69.35+/-4.60, all P<0.01]. Compared with control group, HVHF treatment group could down-regulate mRNA expression of TLR4 in myocardium (t=3.58, P<0.01). Correlation analysis revealed significant positive-correlation between tissue TLR4 mRNA expression and contents of TNF-alpha, IL-6, IL-10 in circulation (r(1)=0.785, r(2)=0.569, r(3)=0.653, all P<0.05). Injury to the myocardium was significantly ameliorated in therapy group compared with control group as shown by electron microscopic observation.


CONCLUSIONS
HVHF can down-regulate mRNA expression of TLR4 in myocardium in LPS induced shock in dogs, and myocardial inflammatory response was alleviated resulting in amelioration of myocardial injury.
Department of Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
Zhen-guo
ZG
Zeng
Jian-guo
JG
Zhang
Rong
R
Jiang
Liang
L
Xia
Ke-jian
KJ
Qian
Chun-ting
CT
Wang
D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects; D006440:Hemofiltration; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D012772:Shock, Septic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4