A rapid and sensitive liquid chromatography-tandem mass spectrometric（LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of pravastatin and aspirin in human plasma.Furo...A rapid and sensitive liquid chromatography-tandem mass spectrometric（LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of pravastatin and aspirin in human plasma.Furosemide was used as an internal standard.Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using methyl tertiary butyl ether.The reconstituted samples were chromatographed on a Zorbax SB-C;8 column by using a mixture of 5 mM ammonium acetate buffer and acetonitrile（20:80,v/v） as the mobile phase at a flow rate of 0.8 mL/min.The calibration curve obtained was linear（r≥0.99） over the concentration range of 0.50-600.29 ng/mL for pravastatin and 20.07-2012.00 ng/mL for aspirin.Method validation was performed as per FDA guidelines and the results met the acceptance criteria.A run time of 2.0 min for each sample made it possible to analyze more than 400 human plasma samples per day.The proposed method was found to be applicable to clinical studies.展开更多
Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been s...Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been suggested as potential prevention or treatment of preeclampsia,although evidence remains inadequate.Herewith,we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide（LPS）-induced rat preeclampsia model,through targeting the TLR4/NF-κB pathway.The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day（GD） 12,（101.33±2.49） mmHg vs.（118.3±1.37） mmHg,P〈0.05] and urine protein level [maximum decline on GD9,（3,726.23± 1,572.86） μg vs.（1,991.03 ±609.37）μg,P〈 0.05],which were elevated following LPS administration.Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats（34.10% vs.8.99%,P〈0.05）.Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment.These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum.Additionally,no obvious abnormalities in fetal liver,brain,and kidney were found after administration of pravastatin.These results provide supportive evidence for use of pravastatin in preventing preeclampsia.展开更多
Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case re...Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AR If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.展开更多
BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-i...BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-inflmmatory cytokines.The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγexpression in the liver and gallbladder epithelium,and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. METHODS:A total of 40 Golden Syrian male hamsters(4 weeks old)were randomly assigned to four groups(basal diet control; basal diet+pavastatin;high cholesterol diet;high cholesterol diet+pravastatin).All hamsters were 11 weeks old at the end of the experiment.The liver,gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARαand PPARγwere performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. RESULTS:In the gallbladder and liver of the hamsters, pravastatin activated the PPARαand PPARγexpression of gallbladder epithelial cells and hepatocytes,and particularly the response of PPARγwas much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. CONCLUSION:Pravastatin is an effective medication to activate PPARs(especially PPARγ)in the liver and the gallbladder epithelium of hamsters,and contributes to the prevention of gallstone formation.展开更多
BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among t...BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor(PPAR)α, PPARγ, liver X receptor α(LXRα), farnesoid X receptor(FXR), ABCG5, ABCG8, and 7α-hydroxylase(CYP7A1) which are directly involved in the cholesterol saturation index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently. CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRαand CYP7A1 in human hepatocytes.展开更多
Indoxyl sulfate (IS) is a typical uremic toxin that extensively accumulates in the plasma of patients with seriously impaired renal function. This study seeks to clarify whether IS exerts a potent modulating effect on...Indoxyl sulfate (IS) is a typical uremic toxin that extensively accumulates in the plasma of patients with seriously impaired renal function. This study seeks to clarify whether IS exerts a potent modulating effect on the hepatic transport of pravastatin, which is a substrate of both organic anion transporting peptides (OATPs) and multidrug resistance-associated protein (Mrp) 2 in rats. When IS is administered intravenously to the normal rats at a dose of 120 μmol/kg;plasma IS levels are approximately 600 μM after 2 min and 100 μM after 120 min. In rats with acute renal failure (ARF) induced by cisplatin, the area under the curve (AUC) was more than 2.5-fold greater compared with that in the normal rats, indicating that IS accumulates in ARF rats. Intravenously administered pravastatin almost disappeared from the plasma by 60 min post-administration and approximately 55% of dose was excreted in the bile within 60 min. This result suggested that pravastatin was efficiently taken up from the sinusoid into hepatocytes via rat OATPs on the sinusoidal membrane and preferentially transported in the bile mediated by Mrp2 on the canalicular membrane. IS administered intravenously at a dose of 120 μmol/kg caused neither an increase in plasma pravastatin levels nor a decrease in its biliary excretion. In conclusion, the present results demonstrate that single intravenous administration of IS does not interfere with the hepatic transport of pravastatin directly in vivo, which is at variance with the results of previous in vitro studies.展开更多
Lung cancer is one of the serious threats to human health and life of malignant diseases, on a global scale; it has become one of the major lung cancer deaths. Due to the growth of the tumor and the main reason is tha...Lung cancer is one of the serious threats to human health and life of malignant diseases, on a global scale; it has become one of the major lung cancer deaths. Due to the growth of the tumor and the main reason is that apoptosis is inhibited, therefore, it can induce apoptosis in lung cancer cells that is an important measure for the treatment of lung cancer, which is one of the effective means to reduce lung cancer mortality. In this paper, A549 human lung adenocarcinoma cell line, for example, has the use of chemical genetics of these emerging technological platforms, research pravastatin on apoptosis in human lung adenocarcinoma A549 intervention, while providing a theoretical basis for the development of new lung cancer therapy.展开更多
Objective To determine whether pravastatin exerts anti-oxidative effects on preventing aortic＂ atherosclerosis via modulating p38 MAPK pathway. Methods Male 8-week-old apoE^-/- mice fed a diet containing 1.25% choles...Objective To determine whether pravastatin exerts anti-oxidative effects on preventing aortic＂ atherosclerosis via modulating p38 MAPK pathway. Methods Male 8-week-old apoE^-/- mice fed a diet containing 1.25% cholesterol （wt/wt） were divided into pravastatin group administered with pravastatin （80 mg. kg ^-1· d^-1 ） and atherosclerosis group administered with PBS; and male 8-week-old C57BL/6J mice fed a normal diet were as control group （ n = 12 ）. In thoracoabdominal aortas of mice, levels of Malondialdehyde （ MDA ） and activities of superoxide dismutase （ SOD ） were measured and expression of phosphorylated p38 MAPK （ p-p38 MAPK） and phosphorylated signal transducer and activator of transcr（ption 1 （pSTAT1） were examined by Western blotting. Results After eight weeks, atherosclerosis in aortic root was significantly prevented by pravastatin. In aortic atherosclerosis lesion, the level of MDA was significantly reduced; adversely the activity, of SOD was increased. Expressions of p-p38 MAPK and pSTAT1 were significantly decreased in aortic atherosclerosis lesion. Conclusion Our results suggests that anti-oxidative mechanisms of pravastatin preventing aortic atherosclerosis may partially depend on modulating p38 MAPK signal pathway.展开更多
Background： Pravastatin （Pra） exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of...Background： Pravastatin （Pra） exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways. Methods： Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester （L-NAME） and used lipopolysaccharide （LPS） from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group （L-NAME ＋ Pra, LPS ＋ Pra, and Control ＋ Pra, n = 8） or normal saline （NS） for the control group （L-NAME ＋ NS, LPS ＋ NS, and Control ＋ NS, n = 8）. Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student＇s t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test. Results： The mean arterial pressure （MAP） and 24-h urinary protein in the L-NAME ＋ NS and LPS ＋ NS groups were significantly higher than the Control ＋ NS group （F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P 〈 0.05） and reduced in the L-NAME ＋ Pra group as compared to the L-NAME ＋ NS group （F = 208.60 for MAP, t = 6.77 for urinary protein; both P 〈 0.05）. Urinary protein was decreased in the LPS ＋ Pra group as compared to the LPS ＋ NS group （t = 5.33; P 〈 0.05）, whereas MAP had no statistical significance （F = 3.37; P 〉 0.05）. Compared to the Control ＋ NS group, the placental efficiency in the L-NAME ＋ NS and LPS ＋ NS groups decreased significantly （t = 3.09 and 2.89, respectively; both P 〈 0.05）; however, no significant difference was observed in L-NAME ＋ Pra and LPS ＋ Pra groups （t = 1.37 and 0.58, respectively; both P 〉 0.05）. Free fatty acid was elevated in the L-NAME ＋ NS group as compared to the Control ＋ NS group （t = 3.99; P 〈 0.05） at day 18 of pregnancy and decreased in the L-NAME ＋ Pra group as compared to the L-NAME ＋ NS group （t = 3.28; P 〈 0.05）; however, no significant change was observed in the LPS model （F = 0.32; P 〉 0.05）. Conclusion： This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.展开更多
Background: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastat...Background: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nio-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. Methods: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n= 8) or normal saline (NS;L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). Results: Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74±0.08 vs. 0.85± 0.06, t=2.95, P<0.05;placenta: 0.63±0.06 vs.0.77±0.06, t=4.64, P<0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r=—0.745, P<0.05;placenta: r=-0.833, P< 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r=—0.733, P<0.05) and serum FFA levels positively with the (r=0.841, P< 0.05) in the L-NAME+ Pra group. Conclusion: The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.展开更多
Objective:To investigate the impacts of Xuezhikang(血脂康,XZK)or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells(CEPCs)in essential hypertensive (EH)patients.Methods:Eighty...Objective:To investigate the impacts of Xuezhikang(血脂康,XZK)or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells(CEPCs)in essential hypertensive (EH)patients.Methods:Eighty-eight EH patients were enrolled into the study and randomly assigned to the antihypertensive drug treatment group(ATH group,29 cases),the pravastatin treatment group(PRA group,29 cases)and the Xuezhikang treatment group(XZK group,30 cases).Patients in the 3 groups were treated with routine antihy...展开更多
文摘A rapid and sensitive liquid chromatography-tandem mass spectrometric（LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of pravastatin and aspirin in human plasma.Furosemide was used as an internal standard.Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using methyl tertiary butyl ether.The reconstituted samples were chromatographed on a Zorbax SB-C;8 column by using a mixture of 5 mM ammonium acetate buffer and acetonitrile（20:80,v/v） as the mobile phase at a flow rate of 0.8 mL/min.The calibration curve obtained was linear（r≥0.99） over the concentration range of 0.50-600.29 ng/mL for pravastatin and 20.07-2012.00 ng/mL for aspirin.Method validation was performed as per FDA guidelines and the results met the acceptance criteria.A run time of 2.0 min for each sample made it possible to analyze more than 400 human plasma samples per day.The proposed method was found to be applicable to clinical studies.
基金funded by the following Grants:National Natural Science Foundation of China,Grant/Award Number:81370724,81571463 and 81401225Innovative Research Program for Postgraduate in Higher Education Institutions of Jiangsu Province for the year 2016,Grant/Award Number:KYLX16_1111
文摘Preeclampsia is associated with over-activation of the innate immune system in the placenta,in which toll-like receptor 4（TLR4） plays an essential part.With their potent anti-inflammatory effects,statins have been suggested as potential prevention or treatment of preeclampsia,although evidence remains inadequate.Herewith,we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide（LPS）-induced rat preeclampsia model,through targeting the TLR4/NF-κB pathway.The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day（GD） 12,（101.33±2.49） mmHg vs.（118.3±1.37） mmHg,P〈0.05] and urine protein level [maximum decline on GD9,（3,726.23± 1,572.86） μg vs.（1,991.03 ±609.37）μg,P〈 0.05],which were elevated following LPS administration.Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats（34.10% vs.8.99%,P〈0.05）.Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment.These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum.Additionally,no obvious abnormalities in fetal liver,brain,and kidney were found after administration of pravastatin.These results provide supportive evidence for use of pravastatin in preventing preeclampsia.
文摘Acute pancreatitis （AP） secondary to drugs is uncommon, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AR If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.
基金supported by a grant from Kyung Hee University Research(20071618)
文摘BACKGROUND:Our earlier study with cultured gallbladder epithelial cells demonstrated that statins(HMG-CoA reductase inhibitors)activate the expression of PPARαand PPARγ, consequently blocking the production of pro-inflmmatory cytokines.The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγexpression in the liver and gallbladder epithelium,and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder. METHODS:A total of 40 Golden Syrian male hamsters(4 weeks old)were randomly assigned to four groups(basal diet control; basal diet+pavastatin;high cholesterol diet;high cholesterol diet+pravastatin).All hamsters were 11 weeks old at the end of the experiment.The liver,gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARαand PPARγwere performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope. RESULTS:In the gallbladder and liver of the hamsters, pravastatin activated the PPARαand PPARγexpression of gallbladder epithelial cells and hepatocytes,and particularly the response of PPARγwas much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder. CONCLUSION:Pravastatin is an effective medication to activate PPARs(especially PPARγ)in the liver and the gallbladder epithelium of hamsters,and contributes to the prevention of gallstone formation.
文摘BACKGROUND: Statins are suggested to preserve gallbladder function by suppressing pro-inflammatory cytokines and preventing cholesterol accumulation in gallbladder epithelial cells. They also affect cross-talk among the nuclear hormone receptors that regulate cholesterol-bile acid metabolism in the nuclei of hepatocytes. However, there is controversy over whether or how statins change the expression of peroxisome proliferator-activated receptor(PPAR)α, PPARγ, liver X receptor α(LXRα), farnesoid X receptor(FXR), ABCG5, ABCG8, and 7α-hydroxylase(CYP7A1) which are directly involved in the cholesterol saturation index in bile. METHODS: Human Hep3B cells were cultured on dishes. MTT assays were performed to determine the appropriate concentrations of reagents to be used. The protein expression of PPARα and PPARγ was measured by Western blotting analysis, and the mRNA expression of LXRα, FXR, ABCG5, ABCG8 and CYP7A1 was estimated by RT-PCR. RESULTS: In cultured Hep3B cells, pravastatin activated PPARα and PPARγ protein expression, induced stronger expression of PPARγ than that of PPARα, increased LXRα mRNA expression, activated ABCG5 and ABCG8 mRNA expression mediated by FXR as well as LXRα, enhanced FXR mRNA expression, and increased CYP7A1 mRNA expression mediated by the PPARγ and LXRα pathways, together or independently. CONCLUSION: Our data suggested that pravastatin prevents cholesterol gallstone diseases via the increase of FXR, LXRαand CYP7A1 in human hepatocytes.
文摘Indoxyl sulfate (IS) is a typical uremic toxin that extensively accumulates in the plasma of patients with seriously impaired renal function. This study seeks to clarify whether IS exerts a potent modulating effect on the hepatic transport of pravastatin, which is a substrate of both organic anion transporting peptides (OATPs) and multidrug resistance-associated protein (Mrp) 2 in rats. When IS is administered intravenously to the normal rats at a dose of 120 μmol/kg;plasma IS levels are approximately 600 μM after 2 min and 100 μM after 120 min. In rats with acute renal failure (ARF) induced by cisplatin, the area under the curve (AUC) was more than 2.5-fold greater compared with that in the normal rats, indicating that IS accumulates in ARF rats. Intravenously administered pravastatin almost disappeared from the plasma by 60 min post-administration and approximately 55% of dose was excreted in the bile within 60 min. This result suggested that pravastatin was efficiently taken up from the sinusoid into hepatocytes via rat OATPs on the sinusoidal membrane and preferentially transported in the bile mediated by Mrp2 on the canalicular membrane. IS administered intravenously at a dose of 120 μmol/kg caused neither an increase in plasma pravastatin levels nor a decrease in its biliary excretion. In conclusion, the present results demonstrate that single intravenous administration of IS does not interfere with the hepatic transport of pravastatin directly in vivo, which is at variance with the results of previous in vitro studies.
文摘Lung cancer is one of the serious threats to human health and life of malignant diseases, on a global scale; it has become one of the major lung cancer deaths. Due to the growth of the tumor and the main reason is that apoptosis is inhibited, therefore, it can induce apoptosis in lung cancer cells that is an important measure for the treatment of lung cancer, which is one of the effective means to reduce lung cancer mortality. In this paper, A549 human lung adenocarcinoma cell line, for example, has the use of chemical genetics of these emerging technological platforms, research pravastatin on apoptosis in human lung adenocarcinoma A549 intervention, while providing a theoretical basis for the development of new lung cancer therapy.
文摘Objective To determine whether pravastatin exerts anti-oxidative effects on preventing aortic＂ atherosclerosis via modulating p38 MAPK pathway. Methods Male 8-week-old apoE^-/- mice fed a diet containing 1.25% cholesterol （wt/wt） were divided into pravastatin group administered with pravastatin （80 mg. kg ^-1· d^-1 ） and atherosclerosis group administered with PBS; and male 8-week-old C57BL/6J mice fed a normal diet were as control group （ n = 12 ）. In thoracoabdominal aortas of mice, levels of Malondialdehyde （ MDA ） and activities of superoxide dismutase （ SOD ） were measured and expression of phosphorylated p38 MAPK （ p-p38 MAPK） and phosphorylated signal transducer and activator of transcr（ption 1 （pSTAT1） were examined by Western blotting. Results After eight weeks, atherosclerosis in aortic root was significantly prevented by pravastatin. In aortic atherosclerosis lesion, the level of MDA was significantly reduced; adversely the activity, of SOD was increased. Expressions of p-p38 MAPK and pSTAT1 were significantly decreased in aortic atherosclerosis lesion. Conclusion Our results suggests that anti-oxidative mechanisms of pravastatin preventing aortic atherosclerosis may partially depend on modulating p38 MAPK signal pathway.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81370723）, and Beijing Municipal Natural Science Foundation （No. 7132215）.
文摘Background： Pravastatin （Pra） exerts protective effects on preeclampsia. Preeclampsia is a multifactorial and pathogenic pathway syndrome. The present study compared the effects of Pra on clinical manifestations of preeclampsia in different pathogenic pathways. Methods： Two different preeclampsia-like mouse models used in this study were generated with Nω-nitro-L-arginine methyl ester （L-NAME） and used lipopolysaccharide （LPS） from day 7 of gestation, respectively. Pra treatment was administered on day 2 after the models were established in each group （L-NAME ＋ Pra, LPS ＋ Pra, and Control ＋ Pra, n = 8） or normal saline （NS） for the control group （L-NAME ＋ NS, LPS ＋ NS, and Control ＋ NS, n = 8）. Maternal weight, serum lipids, the histopathological changes, and lipid deposition in the liver and placenta were observed. The pregnancy outcomes were compared. The blood pressure analysis was carried out on repeated measurements of variance. Student＇s t-test was used for comparing the two groups. The enumeration data were compared by Chi-square test. Results： The mean arterial pressure （MAP） and 24-h urinary protein in the L-NAME ＋ NS and LPS ＋ NS groups were significantly higher than the Control ＋ NS group （F = 211.05 and 309.92 for MAP, t = 6.63 and 8.63 for 24-h urinary protein; all P 〈 0.05） and reduced in the L-NAME ＋ Pra group as compared to the L-NAME ＋ NS group （F = 208.60 for MAP, t = 6.77 for urinary protein; both P 〈 0.05）. Urinary protein was decreased in the LPS ＋ Pra group as compared to the LPS ＋ NS group （t = 5.33; P 〈 0.05）, whereas MAP had no statistical significance （F = 3.37; P 〉 0.05）. Compared to the Control ＋ NS group, the placental efficiency in the L-NAME ＋ NS and LPS ＋ NS groups decreased significantly （t = 3.09 and 2.89, respectively; both P 〈 0.05）; however, no significant difference was observed in L-NAME ＋ Pra and LPS ＋ Pra groups （t = 1.37 and 0.58, respectively; both P 〉 0.05）. Free fatty acid was elevated in the L-NAME ＋ NS group as compared to the Control ＋ NS group （t = 3.99; P 〈 0.05） at day 18 of pregnancy and decreased in the L-NAME ＋ Pra group as compared to the L-NAME ＋ NS group （t = 3.28; P 〈 0.05）; however, no significant change was observed in the LPS model （F = 0.32; P 〉 0.05）. Conclusion： This study suggested that Pra affected the clinical manifestations differently in preeclampsia-like mouse models generated in various pathogenic pathways.
基金grants from the National Natural Science Foundation of China (No. 81370723)Beijing Municipal Natural Science Foundation (No. 7132215).
文摘Background: Fatty acid oxidation (FAO) disorder is involved in the pathogenesis of some cases of preeclampsia (PE). Several show that mammalian target of rapamycin (mTOR) signaling pathway is related to FAO. Pravastatin (Pra) can promote FAO in Nio-nitro-L-arginine methyl ester (L-NAME) PE-like mouse model in our previous study. This study aimed to investigate the effect of mTOR signaling pathway in PE-like model treated with Pra. Methods: Pregnant mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from gestational 7th to 18th day. Giving Pra (L-NAME + Pra, Control + Pra, n= 8) or normal saline (NS;L-NAME + NS, Control + NS, n = 8) from gestational 8th to 18th day, the mice were sacrificed on day 18 and their liver and placental tissues were collected. Then the activation of mTOR and its substrates in the liver and placenta were detected. And the association between mTOR activation and mice were randomly injected with L-NAME as PE-like model group or saline as control group respectively, from serum free fatty acid (FFA) levels and the expression of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) were evaluated using Pearson correlation test. Differences between groups were analyzed using independent t-test or one-way analysis of variance (ANOVA). Results: Both in the maternal liver and placenta, the activation of mTOR protein and its effect on substrates increased significantly in the L-NAME + NS group and decreased significantly in the L-NAME + Pra group. The p-mTOR/mTOR protein ratio decreased in the L-NAME + Pra group significantly than that in the L-NAME + NS group both in liver and placenta (liver: 0.74±0.08 vs. 0.85± 0.06, t=2.95, P<0.05;placenta: 0.63±0.06 vs.0.77±0.06, t=4.64, P<0.05). The activation of mTOR protein in the liver and placenta negatively correlated with the expression of LCHAD in the L-NAME + NS group (liver: r=—0.745, P<0.05;placenta: r=-0.833, P< 0.05) and that in the maternal liver negatively correlated with the expression of LCHAD (r=—0.733, P<0.05) and serum FFA levels positively with the (r=0.841, P< 0.05) in the L-NAME+ Pra group. Conclusion: The inhibition of mTOR signaling pathway might be involved in the regulation of FAO in mouse model treated with Pra.
文摘Objective:To investigate the impacts of Xuezhikang(血脂康,XZK)or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells(CEPCs)in essential hypertensive (EH)patients.Methods:Eighty-eight EH patients were enrolled into the study and randomly assigned to the antihypertensive drug treatment group(ATH group,29 cases),the pravastatin treatment group(PRA group,29 cases)and the Xuezhikang treatment group(XZK group,30 cases).Patients in the 3 groups were treated with routine antihy...
