[Influence and mechanism of peroxisome proliferation activated receptor-alpha expression induced by WY14643 in rat lung with acute lung injury].
OBJECTIVE
To investigate the effect of WY14643 [peroxisome proliferation activated receptor-alpha (PPAR-alpha) activator, 4-cholro-6-(2.3-xylidino)-2-pyrimidinylthio acetic acid] on PPAR-alpha expression in lung of acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its mechanism.


METHODS
One hundred and four male Wistar rats were randomly divided into four groups: control group, ALI group, WY14643 1 mg group and WY14643 3 mg group. Wistar rats were given LPS (5 mg/kg) before intratracheal challenge with WY14643 (1 mg/kg and 3 mg/kg). Rats of all groups were sacrificed at 1, 2, 4, 8 hours after LPS challenge. The levels of PPAR-alpha mRNA in lung were measured by semi quantitative reverse transcription-polymerase chain reaction, the levels of PPAR-alpha protein in rats lung homogenate were measured by Western blot.


RESULTS
The levels of PPAR-alpha mRNA at 2,4 and 8 hours in WY14643 1 mg group and WY14643 3 mg group were significantly higher than that in ALI group (P<0.05 or P<0.01). The levels of PPAR-alpha mRNA at all time in ALI group was significantly lower than that in control group (P<0.01). Meanwhile,the levels of PPAR-alpha protein at all time in WY14643 1 mg group and WY14643 3 mg group were significantly higher than that in ALI group (P<0.01). The level of PPAR-alpha mRNA at 4 hours and 8 hours in WY14643 1 mg group and at 2,4 and 8 hours in WY14643 3 mg group were significantly higher than those in control group too (P<0.05 or P<0.01).


CONCLUSIONS
The expressions of PPAR-alpha mRNA and protein are all significantly low in the lung of rats with acute lung injury. WY14643 may upregulate the level of PPAR-alpha in the lung tissue in rats with acute lung injury.
Jiang
Peng
P
Department of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, China. jipzym@126.com
Wang
Jian-chun
JC
Zhao
Yong-mei
YM
Qian
Gui-sheng
GS
D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; C006253:pirinixic acid