Role of angiotensin II type 1 receptor in activation of nuclear factor-kappaB and activator protein-1 in lung of mice with acute lung injury / 中华烧伤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the role of angiotensin II type 1 (AT1) receptor in activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) in lung of mice with LPS-induced acute lung injury (ALI).</p><p><b>METHODS</b>Eighty-eight BABL/c mice were divided into control group (n = 8), LPS group (n = 40), and LPS + AT1 receptor antagonist ZD7155 group (n = 40) according to the random number table. Puncture of trachea was done in all mice. Mice in LPS + ZD7155 group were intraperitoneally injected with 10 mg/kg ZD7155. Mice in LPS and control groups were intraperitoneally injected with normal saline in the same volume as that of ZD7155. Thirty minutes later, 1 mg/mL LPS was dripped into trachea of mice in LPS and LPS + ZD7155 groups (2 mg/kg). Normal saline in the same volume as that of LPS was dripped into trachea of mice in control group. Lung tissue samples of mice in LPS and LPS + ZD7155 groups were harvested at post dripping hour (PDH) 1, 3, 6, 12, and 24. Lung tissue sample of mice in control group was harvested at PDH 24. Expression of AT1 receptor was determined with Western blot. AP-1 and NF-kappaB activity in lung tissue was detected with electrophoretic mobility shift assay. Data were processed with one-way analysis of variance.</p><p><b>RESULTS</b>The relative expression amount of AT1 receptor protein in lung tissue of mice in LPS group at each time point was increased obviously as compared with that of mice in control group (0.69 +/- 0.28, F = 9.356, with P values all below 0.01), and it peaked at PDH 6 (3.44 +/- 0.90), while that of mice in LPS + ZD7155 group was less than that in LPS group at each time point (F = 9.356, with P values all below 0.01). NF-kappaB activity in mice lung was markedly increased in LPS group at each time point as compared with mice in control group (5.47 +/- 0.08, F = 26.443, with P values all below 0.05), and its peak value in LPS group was found at PDH 3 (52.33 +/- 3.25). While NF-kappaB activity in mice of LPS + ZD7155 group was obviously lower than that in LPS group at each time point (F = 26.443, with P values all below 0.05). AP-1 activity in lung was enhanced significantly in LPS group at each time point as compared with that in control group (2.5 +/- 0.4, F = 34.685, with P values all below 0.05), and the activity peaked at PDH 6 (73.3 +/- 9.5) in LPS group. The activity was obviously weaker in mice in LPS + ZD7155 group as compared with that in LPS group at each time point (F = 34.685, with P values all below 0.05).</p><p><b>CONCLUSIONS</b>AT1 receptor contributes to LPS-induced ALI through activating NF-kappaB and AP-1 in lung tissue.</p>