Effects of specimen preservation and transportation on blood paraquat concentration in rats / 中华劳动卫生职业病杂志

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

Early predictive value of high density lipoprotein cholesterol for secondary acute kidney injury in sepsis patients / 中华烧伤杂志

Objective: To investigate the changes of high density lipoprotein cholesterol (HDL-C) in sepsis patients and its early predictive value for secondary acute kidney injury (AKI) in such patients. Methods: A retrospective case series study was conducted. From June 2019 to June 2021, 232 sepsis patients who met the inclusion criteria were admitted to the Second Hospital of Hebei Medical University, including 126 males and 106 females, aged 24 to 71 years. According to whether complicating secondary AKI, the patients were divided into non-AKI group (n=158) and AKI group (n=74). Data of patients between the two groups were compared and statistically analyzed with independent sample t test or chi-square test, including the sex, age, body mass index (BMI), body temperature, heart rate, primary infection site, combined underlying diseases, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score at admission, and the serum levels of C-reactive protein (CRP), procalcitonin, creatinine, cystatin C, and HDL-C measured at diagnosis of sepsis. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups to screen the independent risk factors for developing secondary AKI in 232 sepsis patients, and the joint prediction model was established based on the independent risk factors. The receiver operating characteristic (ROC) curve of the independent risk factors and the joint prediction model predicting secondary AKI in 232 sepsis patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of the above-mentioned AUC was compared by Delong test, and the sensitivity and specificity under the optimal threshold were compared using chi-square test. Results: The sex, age, BMI, body temperature, heart rate, primary infection site, combined underlying diseases, and CRP level of patients between the two groups were similar (P>0.05). The procalcitonin, creatinine, cystatin C, and scores of APACHE Ⅱ and SOFA of patients in AKI group were all significantly higher than those in non-AKI group (with t values of -3.21, -16.14, -12.75, -11.13, and -12.88 respectively, P<0.01), while the HDL-C level of patients in AKI group was significantly lower than that in non-AKI group (t=6.33, P<0.01). Multivariate logistic regression analysis showed that creatinine, cystatin C, and HDL-C were the independent risk factors for secondary AKI in 232 sepsis patients (with odds ratios of 2.45, 1.68, and 2.12, respectively, 95% confidence intervals of 1.38-15.35, 1.06-3.86, and 0.86-2.56, respectively, P<0.01). The AUCs of ROC curves of creatinine, cystatin C, HDL-C, and the joint prediction model for predicting secondary AKI in 232 sepsis patients were 0.69, 0.79, 0.89, and 0.93, respectively (with 95% confidence intervals of 0.61-0.76, 0.72-0.85, 0.84-0.92, and 0.89-0.96, respectively, P values all below 0.01); the optimal threshold were 389.53 μmol/L, 1.56 mg/L, 0.63 mmol/L, and 0.48, respectively; the sensitivity under the optimal threshold were 76.6%, 81.4%, 89.7%, and 95.5%, respectively; the specificity under the optimal threshold values were 78.6%, 86.7%, 88.6%, and 96.6%, respectively. The AUC quality of cystatin C was significantly better than that of creatinine (z=2.34, P<0.05), the AUC quality and sensitivity and specificity under the optimal threshold of HDL-C were all significantly better than those of cystatin C (z=3.33, with χ2 values of 6.43 and 7.87, respectively, P<0.01) and creatinine (z=5.34, with χ2 values of 6.32 and 6.41, respectively, P<0.01); the AUC quality and sensitivity and specificity under the optimal threshold of the joint prediction model were all significantly better than those of creatinine, cystatin C, and HDL-C (with z values of 6.18, 4.50, and 2.06, respectively, χ2 values of 5.31, 7.23, 3.99, 6.56, 7.34, and 4.00, respectively, P<0.05 or P<0.01). Conclusions: HDL-C level in sepsis patients with secondary AKI is significantly lower than that in patients without secondary AKI. This is an independent risk factor for secondary AKI in sepsis patients with a diagnostic value being superior to that of creatinine and cystatin C. The combination of the aforementioned three indicators would have higher predicative valuable for secondary AKI in sepsis patients.

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>

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>