[The protective effects and mechanisms of peroxisome proliferator-activated receptor-gamma agonist in rats with acute lung injury].
OBJECTIVE
To observe if peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist (troglitazone) was able to alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats, and explore the underlying mechanisms.


METHODS
Seventy-two wistar rats were randomized into the the following groups, the LPS groups (32 rats), and the troglitazone intervention groups (T group, 32 rats) and a control group (8 rats). T groups and LPS groups were divided into 1, 2, 4, 8 h subgroups (n = 8 each) according to the experimental protocol. LPS (5 mg/kg) was administered through the vein in the LPS groups. In the T groups, 15 min after LPS injecting, troglitazone was administrated (3 mg/kg) through the vein. PaO2, myeloperoxidase activity (MPO), lung tissue histopathological changes were observed. Expressions of PPAR-gamma mRNA and TNF-alpha mRNA were assayed by RT-PCR, TNF-alpha levels measured with ELISA, expression of PPAR-gamma protein in lung tissue detected by immunohistochemistry method, and expression of NF-kappaB P65 protein assayed by Western Blot. The data were expressed as mean +/- SD and analyzed with SPSS 10.0 software.


RESULTS
PaO2 in 1, 2, 4, and 8 h groups were (85 +/- 10), (80 +/- 10), (81 +/- 10), (82 +/- 13) mm Hg (1 mmHg =0.133 kPa) in the T groups, (75 +/- 11), (69 +/- 12), (63 +/- 11), (71 +/- 13) mm Hg in the LPS groups, respectively, the difference being significant between groups (F = 4.32, P < 0.05). MPO activity in 2, 4 and 8 h groups were (10.6 +/- 1.2), (14.1 +/- 2.1), (11.1 +/- 1.8) U/g in the LPS groups, (8.2 +/- 0.8), (9.2 +/- 0.9), (8.8 +/- 0.7) U/g in the T groups, and comparison between groups showed statistical significance (F = 14.99, P <0.05). TNF-alpha mRNA expression (A) in 1 h group and 2 h group were 0.68 +/- 0.07, 0.92 +/- 0.05 in the LPS groups and 0.39 +/- 0.07, 0.50 +/- 0.09 in the T groups, and comparison between groups showed statistical significance (q = 3.09, 3.99, P <0.05). TNF-alpha levels in 1 h group and 2 h group in lung homogenate and plasma were (340 +/- 33), (757 +/- 47), (12.3 +/- 1.8), (54.7 +/- 6.6) ng/L in LPS groups, (306 +/- 30), (685 +/- 47), (10.0 +/- 1.7), (46.8 +/- 5.9) ng/L in T groups, the difference between groups being significant(q =3.92, 4.71, 4.81, 5.17, all P<0.05). PPAR-gamma mRNA expression (A) in 1 h, 2 h and 4 h groups were 0.36 +/- 0.05, 0.25 +/- 0.04, 0.30 +/- 0.05 in the LPS groups, 0.39 +/- 0.02, 0.44 +/- 0.05, 0.46 +/- 0.04 in the T groups, the difference between groups being significant (q =6.13, 5.69, 3.72, all P <0.05). NF-kappaB P65 translocated from plasma to nucleus in 1 h and 8 h group; the A values were 0.81 +/- 0.14, 1.91 +/- 0.16, 0.33 +/- 0.06, 2.01 +/- 0.18 in the LPS groups and 1.14 +/- 0.15, 1.06 +/- 0.21, 0.81 +/- 0.14, 1.03 +/- 0.18 in the T groups, comparison between groups showed statistical difference (q = 3.29, 6.25, 5.59, 6.81, all P <0.05).


CONCLUSIONS
PPAR-gamma agonist (troglitazone) decreased the expression levels of inflammatory mediators such as TNF-alpha, reduced infiltration and activation of inflammatory cells in lung tissues, and alleviated LPS-induced through PPAR-gamma upregulation and inhibition of NF-kappaB activity.
Wang
Jian-Chun
JC
Institute of Respiratory Medicine of PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. wjc@mail.tmmu.com.cn
Jiang
Peng
P
Huang
Jian
J
Qian
Gui-Sheng
GS
D055371:Acute Lung Injury / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists* / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D002839:Chromans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077288:Troglitazone