Impack Of Hypothermia On TLR2 Protein Expression And Downstream Inflamematory Downstream Inflammatory Mediator During Acute Lung Injury

Objective:To investigate impact of hypothermia on TLR2 protein expression and downstream inflammatory mediator during acute lung injury.Methods:Male sprague-dawley rats(n=90)were randomly divided into four groups. The ALI model was reproduced by 0.5 mg/kg LPS intratracheal instillation; equivalent saline was instilled intratracheally for control group. In hypothermia group the rectal temperature was lowered to 32-34℃ and control temperature group the rectal temperature was to 36-37℃ 1 hour after LPS instillation. All the rats were killed by bloodletting after LPS or saline instillation 2 hour,7 hour,13 hour. To determine the arterial blood gas respectively before the trickle-down, after the trickle-down 1 hour,2 hour,6 hour,12 hour for the rats of instillation of LPS or saline. The morphological changes in lung tissue of rats were observed under light microscope. TLR2 protein expression was determined by western blotting and MyD88 mRNA, TNF-a mRNA and iNOS mRNA transcriptional level was determined reverse transcription-polymerase chain reaction(RT-PCR).Results:Under the intervention of LPS, oxygen partial pressure of each group was decreased significantly; score of morphological changes in lung tissue of rats was increased obviously; in hypothermia group, temperature controlled group and temperature uncontrolled group, TLR2 protein expression, Myd88 mRNA, TNF-a mRNA and iNOS mRNA transcription of lung tissue was showed an increased trend. At 1 hour and 6 hour, oxygen partial pressure in hypothermia group was better than that in temperature controlled group and temperature uncontrolled group(lh:84.52±8.11 vs.72.59±8.00 and 66.39±4.19, all P<0.05; 6h:73.44±20.62 vs.59.71±2.87 and 55.28±11.99, all P<0.05); at the 12 hour, oxygen partial pressure in temperature controlled group and temperature uncontrolled group exhibited no difference(50.65±3.74 vs.49.02± 6.01 and 46.25±3.73, all P>0.05). At each timepoint, score of morphological changes of lung tissue in hypothermia group was lower than that in temperature controlled group and temperature uncontrolled group(lh:6.04±0.74 vs.7.96± 0.65 and 8.17±0.59, all P<0.001; 6h:9.09±0.80 vs.13.13±1.02 and 13.00±0.98, all P<0.001; 12h:10.79±1.42 vs.13.42±0.68 and 13.38±1.08, all P<0.05); TLR2 protein expression of hypothermia group was lower than that of temperature controlled group and temperature uncontrolled group(1h:0.19±0.03 vs.0.23±0.04 and 0.24±0.05, all P<0.001; 6h:0.30±0.05 vs.0.41±0.10 and 0.45±0.08, all P<0.001; 12h:0.70±0.09 vs.0.94±0.08 and 0.99±0.10, all P<0.001); Myd88 mRNA, iNOS mRNA and TNF-a mRNA transcription level of hypothermia group were lower than that of temperature controlled group and temperature uncontrolled group (MyD88 mRNA 1h:2.25±0.41 vs.3.04±0.30 and 3.14±0.35, all P<0.001; 6h:5.67±0.55 vs.7.01±0.76 and 7.20±0.55, all P<0.001; 12h:7.14±0.60 vs.8.87±0.54 and 9.17±0.73, all P<0.001; TNF-a mRNA 1h:2.52±0.21 vs.2.98±0.23 and 3.04±0.30, all P<0.001; 6h:4.60±0.31 vs.5.52±0.33 and 5.62±0.42, all P<0.001; 12h:6.95±0.77 vs.8.58±0.50 and 8.88±0.51, all P<0.001; iNOS mRNA 1h:1.99±0.16 vs.2.38±0.23 and 2.46±0.16, all P<0.001; 6h:5.17±0.46 vs.6.06±0.40 and 6.21±0.45, all P<0.001; 12h:6.85±0.47 vs.7.68±0.53 and 7.88±0.56, all P<0.001).Conclusion:Hypothermia may downregulate TLR2 protein expression and lowered Myd88 mRNA, iNOS mRNA and TNF-a mRNA expression level, thus reduced lung injury of endotoxin-induced ALI of rats.