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

<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>

Endostar reduces the growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the influence of endostar alone or in combination with cisplatin on tumor growth and metastasis, as well as the inhibition of angiogenesis and lymphangiogenesis in nude mouse models of human cervical cancer.</p><p><b>METHODS</b>HeLa cells were inoculated subcutaneously into the hind flank region of female nu/mice to establish xenograft models. The nude mice were randomly divided into 5 groups: (1) sodium chloride (as control); (2) cisplatin alone; (3) endostar alone; (4) cisplatin plus endostar (10 mg/kg); (5) cisplatin plus endostar (20 mg/kg). The course of all the treatments lasted for 4 weeks. The tumor growth and lymph node metastasis were observed. Immunohistochemical staining was employed to detect the angiogenesis and lymphangiogenesis.</p><p><b>RESULTS</b>(1) Either endostar alone or endostar with cisplatin inhibited the tumor growth significantly than cisplatin and NS (P < 0.05). (2) The rates of lymph node metastasis in the endostar (20 mg/kg) with cisplatin, the endostar (10 mg/kg) with cisplatin, the endostar, the cisplatin and the NS groups were 0 (0/8), 12.5% (1/8), 12.5% (1/8), 62.5% (5/8) and 75.0% (6/8) (P = 0.002), respectively. (3) The MVD of tumor tissue in these five groups were 10.88 +/- 1.38, 10.25 +/- 1.22, 10.83 +/- 2.29, 15.58 +/- 2.31 and 22.08 +/- 1.93, respectively (P < 0.05). The MLD were 5.00 +/- 0.63, 5.17 +/- 0.75, 6.00 +/- 0.63, 14.33 +/- 1.63 and 13.67 +/- 1.21, respectively (P < 0.05).</p><p><b>CONCLUSION</b>Endostar can reduce the tumor growth and metastasis by inhibiting angiogenesis and lymphangiogenesis in nude mouse model of human cervical cancer.</p>

Activation of nuclear factor-kappaB signaling pathway in rat gastric mucosa during stress ulceration / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the time course of nuclear factor-kappaB (NF-kappaB) activation in the process of stress ulcer formation.</p><p><b>METHODS</b>Model of stress ulcer was reproduced by subjecting male Sprague-Dawley rats to water-immersion restraint (WIR) stress. At indicated time after the beginning of WIR stress, animals were sacrificed and cytoplasmic and nuclear protein and total RNA were prepared from gastric corpus mucosal tissues. DNA-binding activity of NF-KB was assessed as an index of NF-kappaB activation with electrophoretic mobility shift assay. Degradation of IkappaBalpha and IkappaBbeta, the inhibitory proteins of NF-kappaB, was analyzed by Western blot analysis. Expression of NF-kappaB dependent genes including tumor necrosis factor-alpha (TNF-alpha) , interleukin-1beta (IL-1beta), cytokine-inducible neutrophil chemoattractant-1 ( CINC-1), intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase (iNOS) was detected with Northern blot analysis.</p><p><b>RESULTS</b>WIR stress induced a rapid biphasic activation of gastric mucosal NF-kappaB within 15 min of the beginning of stress, peaking at 45 min and 360 min. Compared with baseline, NF-kappaB activation by stress was increased (10.6 +/- 1.3) and (8.9 +/- 1.2) fold at 45 min and 360 min, respectively (P < 0.01). Antibody supershift assays revealed that p50/p65 heterodimer was the major active component of mucosal NF-kappaB. Western blot analysis showed that degradation of IkappaBalpha and IkappaBbeta occurred at first and second wave of NF-kappaB activation. Corresponding with the rapid and persistent activation of NF-kappaB, the levels of TNF-alpha, IL-1beta, CINC-1 and ICAM-1 mRNA in gastric mucosa were markedly increased 15 to 30 min after stress, respectively. Up-regulation of iNOS mRNAs was observed 30 to 90 min after stress, and the expression of all of these genes was increased consistently until the end of stress.</p><p><b>CONCLUSION</b>NF-kappaB activation is an early event and may play an important role in proinflammatory gene over-expression in rat gastric mucosa during WIR stress.</p>

Role of p38 mitogen-activated protein kinase in the pathogenesis of stress ulcer / 中华外科杂志

<p><b>OBJECTIVE</b>To determine whether the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of stress ulcer.</p><p><b>METHODS</b>Model of stress ulcer was established with the treatment of rats with water-immersion restraint (WIR) stress. Ulcer index (UI) was macroscopically evaluated as a parameter of gastric mucosal lesions. Expression of phospho- and pan-p38 in gastric mucosa was detected using Western blot analysis. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin 1beta (IL-1beta) gene expressions were analyzed by Northern blot analysis. As indicated in some experiments, rats were pretreated with intravenous injection of the specific p38 MAPK inhibitor CNI-1493 prior to WIR stress and then the changes of UI and TNF-alpha and IL-1beta mRNA expression were examined.</p><p><b>RESULTS</b>The p38 MAPK was persistently activated in the gastric mucosa of rats with WIR stress, with maximal activation after 1 h of stress [(6.8 +/- 3.2) fold of baseline levels, P < 0.01]. Inhibition of p38 MAPK activation with CNI-1493 led to a marked decrease in UI in WIR stress rats. Similarly, the increased gene expression of proinflammatory cytokines TNF-alpha and IL-1beta in gastric mucosa induced by WIR stress were significantly diminished by p38 MAPK inhibition.</p><p><b>CONCLUSION</b>p38 MAPK might have an important role in the pathogenesis of stress ulcer.</p>