Cistanoside compounds were studied as the scavengers of hydroxyl and superoxide anion free radicals with spin trapping ESR method in vitro. Low-temperature ESR technique, experimental technique of immunotoxicology and...Cistanoside compounds were studied as the scavengers of hydroxyl and superoxide anion free radicals with spin trapping ESR method in vitro. Low-temperature ESR technique, experimental technique of immunotoxicology and biochemical method were used to detect the level of reactive oxygen radicals in kidney tissue of rats and SOD level and GSH-Px activity in rat serum. The results indicated that cistanoside compounds could inhibit reactive oxygen free radicals in vitro and prevent and repair the free radical damages for diabetic nephropathy. The experimental data of 揷arbon-particle detection in mouse serum?showed that cistanoside compounds could improve the phagocytotis index of macrophages (Mj) in mice blood and increase the weights of immune organs of mice.展开更多
Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium(Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride(...Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium(Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride(NaCl) and Cd are poorly understood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species(ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase(SOD), catalase(CAT), and peroxidase(POD) of Z. rouxii were significantly enhanced by 2%–6% NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory effect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.展开更多
AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by ...AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.展开更多
Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB t...Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB transcription factor family includes several subunits （p50, p52, p65, c-Rel, and Rel B） that respond to myocardial ischemia. It has been proved that persistent myocyte NF-κB p65 activation in heart failure exacerbates cardiac remodeling. Mechods A recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent protein and anti-NF-κB p65 ribozyme （AAV9-R65-CMV-eGFP） was constructed. The cells were assessed by MTT assay, Annexin V–propidium iodide dual staining to study apoptosis. The expression of P65 and P50 were assessed by Western blot to investigate the under-lying molecular mechanisms. Results After stimulation with H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP decreased H2O2-induced P65 expression. Conclusions AAV9-R65-CMV-eGFP protects H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65 expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential to exert cardioprotective effects against oxidative stress, which might be of great importance to clinical efficacy for cardiovascular disease.展开更多
Microsomal glutathione transferase (MGST1, EC 2.5.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediate...Microsomal glutathione transferase (MGST1, EC 2.5.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.展开更多
Mud crab （Scylla serrata） is an important commercial crustacean in China. An experiment was designed to study the effect of cold stress on S. serrata. After a one-week adaptation at 28℃, the temperature is suddenly...Mud crab （Scylla serrata） is an important commercial crustacean in China. An experiment was designed to study the effect of cold stress on S. serrata. After a one-week adaptation at 28℃, the temperature is suddenly reduced to 4℃. The crabs were sampled every 2 h for 10 h and dissected immediately to measure the enzyme activity. The crabs at room temperature （28℃） were used as the control group. The activity of superoxide dismutase （SOD）, catalase （CAT） and gkttathione peroxidase （GPX）, the content of malondialdehyde （MDA） and the activity of 4 ATPases （Na^＋, K^＋-ATPase, Mg^2＋-ATPase; Ca^2＋-ATPase; Ca^2＋, Mg^2＋-ATPase） were measured biochemically. In contrast to the control group, the SOD activity increased significantly from 2 to 6 h after the cold stress, and then decreased. The CAT and GPX activities increased in 2 h, and then decreased gradually. The content of MDA increased gradually in 4 h. The activity of Na^＋, K^＋-ATPase decreased in 2 h, increased up to the top value at Hour 6, then decreased again. The activities of Mg^2＋-ATPase, Ca^2＋-ATPase and Ca^2＋, Mg^2＋-ATPase increased significantly in 6 h, insignificantly in any other hours. Under cold stress, the activity of antioxidative enzymes in S, serrata was reduced at first then stabilized, ROS-scavenging weakened, and MDA accumulated gradually in the gill after 6 h. The activity of the 4 ATPases in the crab decreased after 6 h, suggesting that the ability to regulate ion concentration has been paralyzed. Therefore, the maximum period to sustain healthy meat in the crab under cold stress is 6 hours.展开更多
This study investigated the inductive effect ofAlexandrium tamarense, a toxic dinoflagellate producing paralytic shell- fish poison, on oxidative stress and apoptosis in hepatopancreas of Chinese shrimp, Fenneropenaeu...This study investigated the inductive effect ofAlexandrium tamarense, a toxic dinoflagellate producing paralytic shell- fish poison, on oxidative stress and apoptosis in hepatopancreas of Chinese shrimp, Fenneropenaeus chinensis. The individuals of E chinensis were exposed to 200 and 1000 cells mL-1 of A. tamarense with their superoxide dismutase （SOD）, glutathione S-transferase （GST） activities, malonyldialdehyde （MDA） concentration, and caspase gene （FcCasp） expression in hepatopancreas determined at 12, 24, 48, 72 and 96 h. In addition, apoptosis in hepatopancreas of E chinensis at 96 h after exposure was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. The hepatopancreatic SOD and GST activities of F. chinensis exposed to 1000 cells mL-1 ofA. tamarense showed a bell-shaped response to exposure time. The hepatopancreatic MDA concentration ofF. chinensis exposed to 1000 cellsmL-1 ofA. tamarense increased gradually from 48 to 96h, and such a trend corresponded to the decrease of GST activity. The hepatopancreatic FcCasp transcript abundance of F. chinensis exposed to 1000 cells mL-1 ofA. tamarense was positively and linearly correlated to MDA concentration. Results of TUNEL assay showed that exposure to 1000 cells mL-1 of A. tamarense induced apoptosis in the hepatopancreas of E chinensis. Our study revealed that A. tamarense exposure influenced the antioxidative status ofF. chinensis and caused lipid peroxidation and apoptosis in the hepatopancreas of shrimp.展开更多
Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a h...Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.展开更多
Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plas...Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plasmids with different genes(wild and mutant QDPR) were constructed. After gene sequencing, they were transfected into human kidney cells(HEK293T). Then, the intracellular production of reactive oxygen species(ROS) and tetrahydrobiopterin(BH4) was detected after cells were harvested. Activations of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4), glutathione peroxidase 3(GPX3), and superoxide dismutase 1(SOD1) were analyzed to observe the oxidative stress after transfection. The expression of the neuronal nitric oxide synthase(n NOS) gene was analyzed by semiquantitative reverse-transcription polymerase chain reaction(RT-PCR). We also detected the activation of transforming growth factor β1(TGF-β1) by enzyme-linked immunosorbent assay(ELISA) to observe the connection of TGF-β1 and oxidative stress. Results: The exogenous wild-type QDPR significantly decreased the expression of n NOS, NOX4, and TGF-β1 and induced the expression of SOD1 and GPX3, but the mutated QDPR lost this function and resulted in excessive ROS production. Our data also suggested that the influence on the level of BH4 had no significant difference between mutated and the wild-type QDPR transfection. Conclusions: Wild-type QDPR played an important role in protecting against oxidative stress, but mutant QDPR failed to have these beneficial effects.展开更多
文摘Cistanoside compounds were studied as the scavengers of hydroxyl and superoxide anion free radicals with spin trapping ESR method in vitro. Low-temperature ESR technique, experimental technique of immunotoxicology and biochemical method were used to detect the level of reactive oxygen radicals in kidney tissue of rats and SOD level and GSH-Px activity in rat serum. The results indicated that cistanoside compounds could inhibit reactive oxygen free radicals in vitro and prevent and repair the free radical damages for diabetic nephropathy. The experimental data of 揷arbon-particle detection in mouse serum?showed that cistanoside compounds could improve the phagocytotis index of macrophages (Mj) in mice blood and increase the weights of immune organs of mice.
基金the financial support of the National Natural Science Foundation of China (Grant Nos. 31101330 and 30972289)the Natural Science Foundation of Shandong Province in China (Grant No. ZR2010CM043)+1 种基金the International Joint Research Program (Grant No. 2010DFA31330)the Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT1188)
文摘Zygosaccharomyces rouxii is a salt-tolerant yeast species capable of removing cadmium(Cd) pollutant from aqueous solution. Presently, the physiological characteristics of Z. rouxii under the stress of sodium chloride(NaCl) and Cd are poorly understood. This study investigated the effects of NaCl and Cd on the growth, oxidative stress and antioxidant enzyme activities of Z. rouxii after stress treatment for 24 h. Results showed that NaCl or Cd alone negatively affected the growth of Z. rouxii, but the growth-inhibiting effect of Cd on Z. rouxii was reduced in the presence of NaCl. Flow cytometry assay showed that under Cd stress, NaCl significantly reduced the production of reactive oxygen species(ROS) and cell death of Z. rouxii compared with those in the absence of NaCl. The activities of superoxide dismutase(SOD), catalase(CAT), and peroxidase(POD) of Z. rouxii were significantly enhanced by 2%–6% NaCl, which likely contributed to the high salt tolerance of Z. rouxii. The POD activity was inhibited by 20 mg L-1Cd while the SOD and CAT activities were enhanced by 8 mg L-1 Cd and inhibited by 20 mg L-1 or 50 mg L-1 Cd. The inhibitory effect of high-level Cd on the antioxidant enzyme activities of Z. rouxii was counteracted by the combined use of NaCl, especially at 6%. This probably accounted for the decrease in Cd-induced ROS production and cell death of Z. rouxii after incubation with NaCl and Cd. Our work provided physiological clues as to the use of Z. rouxii as a biosorbent for Cd removal from seawater and liquid highly salty food.
基金Supported by Research Fellowship from Council of Scientific and Industrial Research,New Delhi,No.NBA2007 of DBT,IAP001 and CLP 261 of NTRF
文摘AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.
基金the National Natural Sci-ence Foundation of China，China Post-doctoral Science Foundation
文摘Background Oxidative stress is a major mechanism underlying the pathogenesis of cardiovascular disease. It can trigger inflammatory cascades which are primarily mediated via nuclear factor-κB （NF-κB）. The NF-κB transcription factor family includes several subunits （p50, p52, p65, c-Rel, and Rel B） that respond to myocardial ischemia. It has been proved that persistent myocyte NF-κB p65 activation in heart failure exacerbates cardiac remodeling. Mechods A recombinant adeno-associated virus serotype 9 carrying enhanced green fluorescent protein and anti-NF-κB p65 ribozyme （AAV9-R65-CMV-eGFP） was constructed. The cells were assessed by MTT assay, Annexin V–propidium iodide dual staining to study apoptosis. The expression of P65 and P50 were assessed by Western blot to investigate the under-lying molecular mechanisms. Results After stimulation with H2O2 for 6 h, H9c2 cells viability decreased significantly, a large fraction of cells underwent apoptosis. We observed a rescue of H9c2 cells from H2O2-induced apoptosis in pretreatment with AAV9-R65-CMV-eGFP. Moreover, AAV9-R65-CMV-eGFP decreased H2O2-induced P65 expression. Conclusions AAV9-R65-CMV-eGFP protects H9c2 cells from oxidative stress induced apoptosis through down-regulation of P65 expression. These observations indicate that AAV9-R65-CMV-eGFP has the potential to exert cardioprotective effects against oxidative stress, which might be of great importance to clinical efficacy for cardiovascular disease.
文摘Microsomal glutathione transferase (MGST1, EC 2.5.1.18) is a membrane bound glutathione transferase extensively studied for its ability to detoxify reactive intermediates, including metabolic electrophile intermediates and lipophilic hydroperoxides through its glutathione dependent transferase and peroxidase activities. It is expressed in high amounts in the liver, located both in the endoplasmic reticulum and the inner and outer mitochondrial membranes. This enzyme is activated by oxidative stress. Binding of GSH and modification of cysteine 49 (the oxidative stress sensor) has been shown to increase activation and induce conformational changes in the enzyme. These changes have either been shown to enhance the protective effect ascribed to this enzyme or have been shown to contribute to cell death through mitochondrial permeability transition pore formation. The purpose of this review is to elucidate how one enzyme found in two places in the cell subjected to the same conditions of oxidative stress could both help protect against and contribute to reactive oxygen species-induced liver injury.
基金the National High-Tech Research and Development Program of China (863 Program) (No. 2002AA603013)
文摘Mud crab （Scylla serrata） is an important commercial crustacean in China. An experiment was designed to study the effect of cold stress on S. serrata. After a one-week adaptation at 28℃, the temperature is suddenly reduced to 4℃. The crabs were sampled every 2 h for 10 h and dissected immediately to measure the enzyme activity. The crabs at room temperature （28℃） were used as the control group. The activity of superoxide dismutase （SOD）, catalase （CAT） and gkttathione peroxidase （GPX）, the content of malondialdehyde （MDA） and the activity of 4 ATPases （Na^＋, K^＋-ATPase, Mg^2＋-ATPase; Ca^2＋-ATPase; Ca^2＋, Mg^2＋-ATPase） were measured biochemically. In contrast to the control group, the SOD activity increased significantly from 2 to 6 h after the cold stress, and then decreased. The CAT and GPX activities increased in 2 h, and then decreased gradually. The content of MDA increased gradually in 4 h. The activity of Na^＋, K^＋-ATPase decreased in 2 h, increased up to the top value at Hour 6, then decreased again. The activities of Mg^2＋-ATPase, Ca^2＋-ATPase and Ca^2＋, Mg^2＋-ATPase increased significantly in 6 h, insignificantly in any other hours. Under cold stress, the activity of antioxidative enzymes in S, serrata was reduced at first then stabilized, ROS-scavenging weakened, and MDA accumulated gradually in the gill after 6 h. The activity of the 4 ATPases in the crab decreased after 6 h, suggesting that the ability to regulate ion concentration has been paralyzed. Therefore, the maximum period to sustain healthy meat in the crab under cold stress is 6 hours.
基金supported by Earmarked Fund for Modern Agro-industry Technology Research System of China (Grant No. CARS-47)Special Fund for Agroscientific Research in the Public Interest of China (Grant No. 201103034)the National ‘863’ Project of China (Grant No. 2012AA10A409)
文摘This study investigated the inductive effect ofAlexandrium tamarense, a toxic dinoflagellate producing paralytic shell- fish poison, on oxidative stress and apoptosis in hepatopancreas of Chinese shrimp, Fenneropenaeus chinensis. The individuals of E chinensis were exposed to 200 and 1000 cells mL-1 of A. tamarense with their superoxide dismutase （SOD）, glutathione S-transferase （GST） activities, malonyldialdehyde （MDA） concentration, and caspase gene （FcCasp） expression in hepatopancreas determined at 12, 24, 48, 72 and 96 h. In addition, apoptosis in hepatopancreas of E chinensis at 96 h after exposure was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. The hepatopancreatic SOD and GST activities of F. chinensis exposed to 1000 cells mL-1 ofA. tamarense showed a bell-shaped response to exposure time. The hepatopancreatic MDA concentration ofF. chinensis exposed to 1000 cellsmL-1 ofA. tamarense increased gradually from 48 to 96h, and such a trend corresponded to the decrease of GST activity. The hepatopancreatic FcCasp transcript abundance of F. chinensis exposed to 1000 cells mL-1 ofA. tamarense was positively and linearly correlated to MDA concentration. Results of TUNEL assay showed that exposure to 1000 cells mL-1 of A. tamarense induced apoptosis in the hepatopancreas of E chinensis. Our study revealed that A. tamarense exposure influenced the antioxidative status ofF. chinensis and caused lipid peroxidation and apoptosis in the hepatopancreas of shrimp.
文摘Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.
基金supported by the National Natural Science Foundation of China(No.81130066)the International Cooperation and Exchanges of the National Natural Science Foundation of China(No.81620108031)
文摘Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plasmids with different genes(wild and mutant QDPR) were constructed. After gene sequencing, they were transfected into human kidney cells(HEK293T). Then, the intracellular production of reactive oxygen species(ROS) and tetrahydrobiopterin(BH4) was detected after cells were harvested. Activations of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4), glutathione peroxidase 3(GPX3), and superoxide dismutase 1(SOD1) were analyzed to observe the oxidative stress after transfection. The expression of the neuronal nitric oxide synthase(n NOS) gene was analyzed by semiquantitative reverse-transcription polymerase chain reaction(RT-PCR). We also detected the activation of transforming growth factor β1(TGF-β1) by enzyme-linked immunosorbent assay(ELISA) to observe the connection of TGF-β1 and oxidative stress. Results: The exogenous wild-type QDPR significantly decreased the expression of n NOS, NOX4, and TGF-β1 and induced the expression of SOD1 and GPX3, but the mutated QDPR lost this function and resulted in excessive ROS production. Our data also suggested that the influence on the level of BH4 had no significant difference between mutated and the wild-type QDPR transfection. Conclusions: Wild-type QDPR played an important role in protecting against oxidative stress, but mutant QDPR failed to have these beneficial effects.
