Study the effects of Salvia miltiorrhiza monomer IH764-3 on the expression of matrix metalloproteinase in lungs of rats exposed to Paraquat (PQ) / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To observe the expression of the matrix metalloproteinase 2 (MMP-2) and membrane-type 1 metalloproteinase (MT1-MMP) in lung of rats exposed to paraquat (PQ) and the effects of Salvia miltiorrhiza monomer IH764-3 on above expression.</p><p><b>METHODS</b>Ninety adult healthy Sprague-Dawley (SD) rats were randomly divided into the control group (group A, 6 rats), the exposure group (group B, 42 rats) and the group treated by Salvia miltiorrhiza monomer IH764-3 (group C, 42 rats). The group B and C were treated intragastrically with 1ml of PQ (50 mg/kg), and the group A was treated intragastrically with normal saline. The group C was treated intraperitoneally with 1 ml Salvia miltiorrhiza monomer IH764-3 at the dose of 40 mg/kg a day. The group A and B were treated intraperitoneally with 1 ml normal saline day. The expression of MMP-2 and MT1-MMP was detected on the 1st, 3rd, 7th, 14th, 21st, 28th and 35th days after exposure for all groups.</p><p><b>RESULTS</b>As compared with the expression level (0.305 ± 0.045) of MMP-2 mRNA in group A, the expression levels of MMP-2 mRNA in Group B significantly increased, which were 0.654 ± 0.077, 0.623 ± 0.051, 0.637 ± 0.024, 0.533 ± 0.043 and 0.552 ± 0.050 on the 1st, 3rd, 7th, 14th, 21st days after exposure, respectively (P < 0.01). As compared with group A, the the expression levels of MMP-2 mRNA on the 1st, 3rd, 7th days in Group C slightly increased, but the expression levels of MMP-2 mRNA on the 1st, 3rd, 7th, 14th, 21st days in Group C were 0.523 ± 0.074, 0.567 ± 0.097, 0.514 ± 0.058, 0.359 ± 0.018 and 0.374 ± 0.020, respectively, which were significantly lower than those in group B (P < 0.01). As compared with the expression level (0.391 ± 0.058) of MT1-MMP mRNA in group A, the expression levels of MT1-MMP mRNA in Group B significantly increased, which were 0.796 ± 0.021, 0.762 ± 0.043, 0.590 ± 0.010, 0.803 ± 0.076 and 0.680 ± 0.034 on the 1st, 3rd, 7th, 14th and 21st days after exposure, respectively (P < 0.01). As compared with group A, the expression levels of MT1-MMP mRNA in Group C significantly increased, which were 0.594 ± 0.010, 0.653 ± 0.044 and 0.564 ± 0.009 on the 1st, 3rd and 21st days after exposure, respectively (P < 0.01). The expression levels of MT1-MMP mRNA in Group C were significantly lower than those in group B (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>The expression changes of MMP-2 and MT1-MMP genes of lungs in rats intragastrically exposed to PQ could result in the unbalance the synthesis and degradation of ECM, which may be a cause of lung fibrosis. The Salvia miltiorrhiza monomer IH764-3 could affect the expression of MMP-2 and MT1-MMP genes to a certain extent, resulting in the reduction of lung fibrosis.</p>

Expression of nuclear factor kappaB and tumor necrosis factor α in lung tissue of paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the expression of nuclear factor kappa B (NF-kgr;B) and tumor necrosis factor α (TNF-α) in lung tissue of acute paraquat poisoned rats.</p><p><b>METHODS</b>68 male Wistar rats were randomly divided into 2 groups: the control group (n = 8), the intoxication group (n = 60). On the 1st, the 3rd, the 7th, the 14th and the 28th day after intoxication, the expression of NF-κB p65 and TNF-α in lung tissue were detected by LSAB immunohistochemistry (IH) staining. Meanwhile, the level of malondialdehyde (MDA) in plasma, and lung homogenate, the content of malondialdehyde (HPY) in lung homogenate were detected.</p><p><b>RESULTS</b>The levels of MDA in plasma on the 1st, the 3rd, the 7th day and in lung homogenate on the 1st, the 3rd day of the intoxication group [in plasma: (10.15 ± 3.15), (6.97 ± 1.65) and (5.44 ± 0.66) nmol/ml; in lung homogenate: (10.20 ± 2.43), (10.71 ± 171) nmol/ml] were significantly higher than that of the control group [in plasma: (3.84 ± 1.04) nmol/ml, in lung homogenate: (7.66 ± 0.66) nmol/ml]. The content of HPY in lung homogenate on the 14th and the 28th day after intoxication [(19.98 ± 2.86), (26.06 ± 4.06) µg/0.1 g lung homogenate] were higher than that of the control group [(8.80 ± 1.26) µg/0.1 g lung homogenate] significantly. The expression of NF-κB p65 and TNF-α in lung tissue were both significantly increased on the first day and the 3rd day of the intoxication group compared with the control group and weakened obviously after the 7th day.</p><p><b>CONCLUSION</b>Acute paraquat poisoning can induce increased expression of both NF-κB p65 and TNF-α in lung tissue; the enhanced activity of NF-κB may take part in the process of pulmonary injury in PQ poisoning.</p>

Pathologic changes and expression of Heme oxygenase-1 in paraquat-induced renal injury / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To study the mechanism of paraquat-induced renal injury in rats.</p><p><b>METHODS</b>Adult healthy Sprague-Dawley (SD) rats (female and male in half) were randomly divided into two groups, the control group and the paraquat poisoned group. The rats in the paraquat poisoned group were treated with PQ (25 mg/kg) intraperitoneally while the rats in the control group were treated with the same dose of normal saline. Its histopathological change was observed and the expression of HO-1 and the mRNA expression of HO-1 were detected by RT-PCR at 3rd h, 6th h, 12th h, on 1st d, 2nd d, 3rd d and 5th d.</p><p><b>RESULTS</b>(1) In the control group, the tissue structure was clear without edema, vacuolar degeneration, cloudy swelling and necrosis. In the paraquat poisoned group, there were obvious lesions in the renal tubule of cortical part, including cellular swelling, the narrow cannula, the mesenchymal congestion and edema. These pathologic changes gradually became more severe, reached the peak on the 1st day, and did not relieve until the end of this study; there was the karyopyknosis and the cyto-architecture disappeared in some severe cases; Some glomerulus and medulla were also involved. (2) In the control group, there was no or weak expression of HO-1 and HO-1 mRNA. At the 3rd hour, the expressions of HO-1 in the paraquat poisoned group were observed in the membrane and cytoplasm of renal tubular epithelial cell of cortical part. Immunohistochemistry score (IHS) in the paraquat poisoned group was higher than that in the control group (P<0.05), except the HIS of the 5th day. At the 3rd hour, the expression of HO-1 mRNA increased, reached the peak on the 1st day, and then decreased. The expression of HO-1 mRNA was (0.53 +/- 0.21), (0.55 +/- 0.31), (0.56 +/- 0.22), (0.64 +/- 0.14) and (0.43 +/- 0.25) at the time point other than on the 3rd and 5th day. It showed statistical difference between the paraquat poisoned group and the control group from the 3rd hour to the 2nd day (P<0.05).</p><p><b>CONCLUSION</b>The mechanism of paraquat induced-renal injury is multiple. The higher expression of HO-1 and HO-1 mRNA were involved in the procedures of paraquat-induced renal injury.</p>

Changes of p38 MAPK and nuclear factor-kappa B in lung tissue of acute paraquat poisoned rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate NF-kappaB activity and the expression of phosphorylated p38 MAPK protein in lung tissue of acute paraquat poisoned rats and the effect of MT.</p><p><b>METHODS</b>One hundred and twenty-eight Sprague-Dawley (SD) rats were randomly divided into three experimental groups: poisoned group, MT group and control group. On the 1st, the 3rd, the 7th and the 14th day after exposure, levels of malondialdehyde (MDA) in serum were detected, NF-kappaB activity in the lung tissues was assessed by electrophoresis mobility shift assay (EMSA), the expression of the phosphorylated p38 MAPK was evaluated by Western blot method, the lung pathological changes of rats were observed.</p><p><b>RESULTS</b>The level of malondialdehyde (MDA) in serum increased significantly in poisoned group on the 1st day (4.45 +/- 1.23), the 3rd day (3.77 +/- 1.12) and the 7th day (2.84 +/- 0.96) nmol/ml compared with that in control group (1.36 +/- 0.52) nmol/ml (P < 0.01). There was a significant decrease in MT group on the 1st day (2.68 +/- 0.85), the 3rd day (1.97 +/- 0.74) and the 7th day (1.53 +/- 0.62) nmol/ml compared with poisoned group (P < 0.05). The expression of the phosphorylated p38 MAPK and NF-kappaB activity in lung tissue of poisoned group significantly increased compared with control group (P < 0.01). There was a significant decrease in NF-kappaB activity and expression of the phosphorylated p38 MAPK in the lung tissues in MT group compared with poisoned group (P < 0.05).</p><p><b>CONCLUSION</b>NF-kappaB and p38 MAPK could play an important role in lung injury of poisoned rats. MT may inhibit the expression of NF-kappaB and phosphorylated p38 MAPK, and therefore might have the therapeutical effect on acute paraquat poisoning.</p>

Effects of high dose ambroxol on lung injury induced by paraquat in rats / 中华劳动卫生职业病杂志

<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>

Effect of baicalin on expression of heme oxygenase-1 in lung injury of rats associated with paraquat poisoning / 中华劳动卫生职业病杂志

<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>

Propofol protecting rats from paraquat induced lung injury / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the protective efficacy of propofol against paraquat induced lung injury.</p><p><b>METHODS</b>One hundred and twenty-eight male Wistar rats were randomizedly divided into three groups: the control group (n = 8), the intoxication group (n = 60) and the propofol group (n = 60). One hundred and twenty rats were once administered with 5 mg/kg paraquat (PQ) by the intragastrical injection to establish the model of PQ induced lung injury. The propofol of 10 mg/kg was administered intraperitoneally in the propofol group (60 rats) twice a day for four consecutive days one hour after the rats were intoxicated while the normal saline of the same amount as propofol in the propofol group was administered in the intoxication group (60 rats) one hour after the rats were intoxicated. The intragastrical injection of 1 mg/kg normal saline was administered once in the control group (8 rats). On the first, the third, the seventh, the 14th and the 28th day after treating, the level of malondialdehyde (MDA) in plasma, bronchoalveolar lavage fluid (BALF) and lung homogenate, and the content of hydroxyproline (HPY) in lung homogenate, the cell count of BALF were detected. Meanwhile, pathological changes of lung were examined under optical microscope.</p><p><b>RESULTS</b>The level of MDA in plasma on the first, the third and the seventh day and in BALF and lung homogenate on the first and the third day in the propofol group [in plasma: (4.31 +/- 0.94), (4.04 +/- 0.87) and (3.24 +/- 1.14) nmol/ml; in BALF: (3.47 +/- 1.09) and (2.79 +/- 1.11) nmol/ml; in lung homogenate: (7.54 +/- 0.63) and (8.41 +/- 1.23) nmol/ml] were significantly lower than those in the intoxication group [in plasma: (10.15 +/- 3.15), (6.97 +/- 1.6 5) and (5.44 +/- 0.66) nmol/ml; in BALF: (5.58 +/- 1.19) and (4.86 +/- 1.89) nmol/ml; in lung homogenate: (10.20 +/- 2.43) and (10.71 +/- 171) nmol/ml, P < 0.05 or P < 0.01]. The total cell count of BALF on the first, the third and the seventh day after intoxication in the propofol group was significantly less than that in the intoxication group respectively (P < 0.05). The histological changes such as alveolar edema, hemorrhage and inflammatory cell infiltration in the propofol group were less than those in the PQ group.</p><p><b>CONCLUSION</b>Propofol could reduce the level of MDA and relieve paraquat induced lung injury.</p>

Influence of ambroxol on paraquat-induced lung tissue injury and change of pulmonary surfactant-associated protein A in the experimental rats / 中华劳动卫生职业病杂志

<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>