BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-...BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.展开更多
BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects ...BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects,but its specific mechanism is not clear.In this study,a rat model of type 2 diabetes was established by administration of a high-sugar,high-fat diet combined with low-dose streptozotocin(STZ)to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms.AIM To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms.METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into a control group,model group,low-dose liraglutide group,and high-dose liraglutide group.Control rats were fed a standard diet,while model group and intervention group rats were fed high-sugar,high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes.The low-dose and highdose intervention groups received 100μg/kg and 200μg/kg liraglutide,respectively,once daily by subcutaneous injection.The control and model groups were given an equivalent volume of physiological saline for 8 wk.Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining,and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lowerin the liraglutide-treated groups than in the model group,with a more significant decrease being observed in the high-dose group than in the low-dose group.RTPCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group,with the high-dose group exhibiting a more significant decrease than the low-dose group.CONCLUSION Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.展开更多
This paper presents model tests(macro aspect)and microstructure tests(micro aspect)for investigating the consolidation behavior of Tianjin dredged clay using the prefabricated vertical drain air-booster vacuum preload...This paper presents model tests(macro aspect)and microstructure tests(micro aspect)for investigating the consolidation behavior of Tianjin dredged clay using the prefabricated vertical drain air-booster vacuum preloading(PAVP)and tube air-booster vacuum preloading(TAVP)methods.The mechanism of air-booster vacuum preloading(AVP)using a spring-like system is explained.The main difference between these two methods is the air-boosting equipment.A new anticlogging air-booster prefabricated vertical drain(PVD)is used in the PAVP technique and a self-designed air-booster tube is used in the TAVP technique.In the model tests,a comparison of the variables that are monitored during reinforcement(vacuum pressure,surface settlement,water discharge,and pore-water pressure)and after reinforcement(water content,dry density,and vane shear strength)is conducted.The results indicate that the consolidation behavior of Tianjin dredged clay using the PAVP method is better than that using the TAVP method.PAVP more efficiently mitigates the issue of water-draining PVD clogging and significantly accelerates drainage consolidation.In addition,in the microstructure tests,a comparison of the variables that are monitored after reinforcement(via scanning electron microscopy(SEM)and mercury intrusion porosimetry(MIP))is conducted,and the results further explain the model test results.展开更多
基金Supported by Shanxi Provincial Natural Science Foundation,No.201701D121159Shanxi Provincial Health and Family Planning Commission,No.2014016Health Commission of Shanxi Province,No.2019020.
文摘BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.
文摘BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects,but its specific mechanism is not clear.In this study,a rat model of type 2 diabetes was established by administration of a high-sugar,high-fat diet combined with low-dose streptozotocin(STZ)to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms.AIM To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms.METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into a control group,model group,low-dose liraglutide group,and high-dose liraglutide group.Control rats were fed a standard diet,while model group and intervention group rats were fed high-sugar,high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes.The low-dose and highdose intervention groups received 100μg/kg and 200μg/kg liraglutide,respectively,once daily by subcutaneous injection.The control and model groups were given an equivalent volume of physiological saline for 8 wk.Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining,and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lowerin the liraglutide-treated groups than in the model group,with a more significant decrease being observed in the high-dose group than in the low-dose group.RTPCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group,with the high-dose group exhibiting a more significant decrease than the low-dose group.CONCLUSION Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.
基金Project supported by the National Key Research and Development Program of China(No.2017YFC0805402)the Open Project of the State Key Laboratory of Disaster Reduction in Civil Engineering(No.SLDRCE17-01),Chinathe National Natural Science Foundation of China(No.51908406)。
文摘This paper presents model tests(macro aspect)and microstructure tests(micro aspect)for investigating the consolidation behavior of Tianjin dredged clay using the prefabricated vertical drain air-booster vacuum preloading(PAVP)and tube air-booster vacuum preloading(TAVP)methods.The mechanism of air-booster vacuum preloading(AVP)using a spring-like system is explained.The main difference between these two methods is the air-boosting equipment.A new anticlogging air-booster prefabricated vertical drain(PVD)is used in the PAVP technique and a self-designed air-booster tube is used in the TAVP technique.In the model tests,a comparison of the variables that are monitored during reinforcement(vacuum pressure,surface settlement,water discharge,and pore-water pressure)and after reinforcement(water content,dry density,and vane shear strength)is conducted.The results indicate that the consolidation behavior of Tianjin dredged clay using the PAVP method is better than that using the TAVP method.PAVP more efficiently mitigates the issue of water-draining PVD clogging and significantly accelerates drainage consolidation.In addition,in the microstructure tests,a comparison of the variables that are monitored after reinforcement(via scanning electron microscopy(SEM)and mercury intrusion porosimetry(MIP))is conducted,and the results further explain the model test results.
