الملخص
<p><b>OBJECTIVE</b>To investigate the change of JNK and c-Jun in lung injury associated with paraquat poisoning of rats.</p><p><b>METHODS</b>46 Rats were randomly divided into four groups: PQ group (n = 12), control group (n = 10), PQ + ZnPP group (n = 12) and PQ + Hm group (n = 12). The rats were injected with 2% PQ (25 mg/kg, ip) in PQ group. ZnPP and Hemin (10 mg/kg, 10 mg/ml) were injected through inguinal vein before intraperitoneal administration of 2% paraquat in PQ + ZnPP group and PQ + Hm group respectively. The rats were injected NS (1 ml/kg, ip) in control group. HE dyeing of lung tissue and MDA content of plasma were used for estimating the injury of lung tissue. The content of CO in the lung tissue was determined. The expression of HO-1 mRNA of the lung tissue was detected by the reverse transcription-polymerase chain reaction. The phosphorylation of JNK and c-Jun was evaluated by Western blot analysis.</p><p><b>RESULTS</b>The degree of lung injury in PQ group and PQ + ZnPP group was higher than that in control group and PQ + Hm group. But in PQ + Hm group the degree of lung injury was lower. The content of MDA in PQ group and PQ + ZnPP group was higher than that in control group and PQ + Hm group (P < 0.01). The content of MDA in PQ + Hm group was higher than that in control group (P < 0.05). The content of CO in lung tissue in PQ group, PQ + ZnPP group and PQ + Hm group was and (1.08 +/- 0.15 mg/L) respectively, and higher than that in control group (P < 0.01). The content of CO in lung tissue in PQ + Hm group was significantly higher than that in PQ + ZnPP group (P < 0.01). The expression of HO-1 and the phosphorylation of JNK (55.24 +/- 9.34, 38.15 +/- 10.71, 128.55 +/- 19.43) and c-Jun (23.16 +/- 4.85, 15.49 +/- 3.13, 44.89 +/- 10.37) were increased remarkably in PQ group, PQ + ZnPP group and PQ + Hm group. Those in PQ + Hm group were higher significantly than PQ group and PQ + ZnPP group (P < 0.01). Those in PQ + ZnPP group were lower than PQ group (P < 0.05).</p><p><b>CONCLUSION</b>The increase of CO of lung tissue in rats at the lung injury associated with paraquat poisoning reduces the acute lung injury of rats. The level of JNK and c-Jun phosphorylation increases obviously, especially after Hemin is utilized.</p>
الموضوعات
Animals , Male , Rats , Acute Lung Injury , Metabolism , Disease Models, Animal , JNK Mitogen-Activated Protein Kinases , Metabolism , Lung , Metabolism , Paraquat , Poisoning , Proto-Oncogene Proteins c-jun , Metabolism , Rats, Sprague-Dawleyالملخص
<p><b>OBJECTIVE</b>To evaluate the protective effect of high dose ambroxol, a mucoactive drug, on acute lung injury caused by paraquat in rats.</p><p><b>METHODS</b>One hundred and thirty-six healthy male Sprague-Dawley rats were randomly divided into three groups: control group (n = 24) injected with normal saline intraperitoneally, PQ group (n = 56) [(2% paraquat (25 mg/kg) injected into peritoneal cavity on the first day)] and AT group (n = 56) ambroxol 35 mg/kg was injected into peritoneum daily after paraquat intoxication once daily for 7 consecutive days. The arterial gas was determined and the extent of lung injury was assessed by measuring the ratio of wet to dry weight (W/D) and protein content in BALF, the WBC count, the percentage of PMN, the content of malondialdehyde (MDA) and the levels of superoxide dismutase (SOD) in the blood and BALF respectively. Left lung tissue was observed through both light microscope and electron microscope (TEM).</p><p><b>RESULTS</b>The white cell count and the content of protein in the blood and the BALF of PQ group were significantly higher than those of the control group (P < 0.05 or P < 0.01). On the 7th day, the content of MDA 9 [(8.12 +/- 1.12) nmol/ml] in the serum of PQ group was significantly higher than the control group and the GSH-Px activity [(1256.8 +/- 133.2) U/ml] was significantly lower than the control group (P < 0.01). The white cell count and the content of protein in the blood and the BALF of AT group were significantly lower than the PQ group (P < 0.05 or P < 0.01). On the 7th day, the content of MDA in the serum of the AT group [(4.86 +/- 0.75) nmol/ml] was significantly lower than the PQ group and the GSH-Px activity [(1509.5 +/- 183.0) U/ml] and the SOD activity [(3903.2 +/- 374.7) U/ml] were significantly higher than the PQ group (P < 0.01). Under optical and electronic microscopes, the injury of lung tissue was reduced after large dose of ambroxol was administered.</p><p><b>CONCLUSION</b>Treatment with ambroxol (35 mg/kg) could influence the status of oxidative stress in lung and alleviate lung injury induced by paraquat. Ambroxol has obviously therapeutic effect on paraquat poisoning.</p>
الموضوعات
Animals , Male , Rats , Acute Lung Injury , Drug Therapy , Metabolism , Pathology , Ambroxol , Pharmacology , Therapeutic Uses , Disease Models, Animal , Lung , Metabolism , Pathology , Oxidative Stress , Paraquat , Poisoning , Rats, Sprague-Dawleyالملخص
<p><b>OBJECTIVE</b>To investigate the influence of ambroxol on paraquat poisoning induced acute lung tissue injury and the change of pulmonary surfactant associated protein A in the experimental rats.</p><p><b>METHODS</b>One hundred and twenty healthy adult male Sprague-Dawley rats were randomizedly assigned into normal saline (NS) group (n = 24), paraquat poisoning induced lung tissue injury model (PQ) group (n = 48) and ambroxol treatment (AT) group (n = 48). The indexes were observed among the three groups comprising the mortality rate, the change of arterial blood PaCO(2) and PaO(2), the ratio of wet to dry lung tissue (W/D), the change of the lung tissue under light and electric microscope respectively, and the expression of pulmonary surfactant associated protein A.</p><p><b>RESULTS</b>The mortality rate of rats in the PQ group was 50.0% on the seventh day while the mortality rate in the AT group was 25.0%. The level of arterial blood PaCO(2) in the PQ group (6.94 +/- 0.8) kPa was significantly higher than that in the AT group (6.12 +/- 0.5) kPa and the NS group (4.6 +/- 0.4) kPa. The level of arterial blood PaO(2) in the PQ group (6.98 +/- 1.1) kPa was significantly lower than that in the AT group (8.25 +/- 0.7) kPa and the NS group (12.7 +/- 0.8) kPa. There were significant differences among the groups (P < 0.05). The degree of lung tissue injury was severe in PQ group and relieved in AT group. The expression of pulmonary surfactant associated protein A was significantly decreased in PQ group 13.22% +/- 2.21% on the seventh day, compared with that in the AT group (21.82% +/- 3.67%) (P < 0.05). The expression of pulmonary surfactant associated protein A in AT group was significantly higher in the AT group (18.97% +/- 0.91%) than that in the PQ group on the seventh day (P < 0.05).</p><p><b>CONCLUSION</b>Ambroxol plays a role in facilitating synthesis and secretion of pulmonary surfactant protein A and relieves the lung tissue injury induced by paraquat poisoning.</p>
الموضوعات
Animals , Male , Rats , Ambroxol , Pharmacology , Immunohistochemistry , Lung , Metabolism , Pathology , Paraquat , Poisoning , Pulmonary Surfactant-Associated Protein A , Random Allocation , Rats, Sprague-Dawley , Respiratory Distress Syndrome , Metabolism , Pathologyالملخص
<p><b>OBJECTIVE</b>To investigate the effect of baicalin (Bai) on lung injury, the level of TNF-alpha in cultured liquid of pulmonary interstitial macrophage and the expression of heme oxygenase-1 (HO-1) in lung injury associated with paraquat poisoning.</p><p><b>METHODS</b>Rats were randomizedly divided into four groups: control group, PQ group, Bai group (Bai, 300 mg.kg(-1).d(-1)) and simple Bai group (Bai, 300 mg. kg(-1).d(-1)) (n = 10 in each group). The 2% PQ was injected (25 mg/kg) in PQ group. Bai was injected in the rats (300 mg.kg(-1).d(-1) x 3 d) through caudal vein after paraquat poisoning in Bai group. In simple Bai group, Bai was injected in the healthy rats (300 mg.kg(-1).d(-1) x 3 d). The samples were obtained three days after intraperitoneal administration of 2% paraquat (25 mg/kg). The injury of lung was estimated with HE dyeing and electron microscope. Pulmonary interstitial macrophage (PIM) were obtained, and then cultured for 24 hours. The content of TNF-alpha was evaluated. The expression of HO-1 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). The expression of HO-1 protein was evaluated by Western blot analysis.</p><p><b>RESULTS</b>The lung tissue was normal in control group and simple Bai group. The degree of lung injury in PQ group was higher than that in control group by HE dyeing and electron microscope observation. The level of TNF-alpha expression in cultured PIM in Bai group [(484.2 +/- 39.5) microg/L] was lower than that in PQ group [(790.2 +/- 35.0) microg/L], but higher than that in the control group [(121.6 +/- 19.2) microg/L] (P < 0.05). The expression of HO-1 mRNA and protein [(59.8 +/- 5.40) and (122.0 +/- 31.98)] in Bai group were higher than those in PQ group [(45.9 +/- 5.82) and (77.92 +/- 10.23)] (P < 0.05).</p><p><b>CONCLUSION</b>The lung injury associated with paraquat poisoning was alleviated by baicalin, which was possibly related to the decrease of level of TNF-alpha in cultured PIM and the increase of the expression of HO-1 mRNA and protein.</p>