ABSTRACT
Objective@#To investigate the effects of astragalus polysaccharides (APS) on insulin resistance and nuclear factor-related factor 2 (Nrf2) -antioxidant response element (ARE) pathway in gestational diabetic rats.@*Methods@#Pregnant Sprague Dawley (SD) rats were divided into normal pregnancy group (control group), model group [gestational diabetes mellitus (GDM) group], low-dose astragalus polysaccharide group (APS-L group), middle-dose astragalus polysaccharide group (APS-M group), high-dose astragalus polysaccharide group (APS-H group), pioglitazone group (Pio group). GDM rat model was established by intraperitoneal injection of streptozotocin (STZ). The levels of fasting blood glucose (FBG), fasting insulin (FINS), adiponectin (APN), tumor necrosis factor-α (TNF-α), Leptin, malondialdehyde (MDA), and superoxde dismutase (SOD) were measured before delivery and 20 days after pregnancy, then the insulin resistance index was calculated; histopathological changes of pancreas were observed by hematoxylin-eosin(HE) staining; the expressions of Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl cysteine synthase (γ-GCS)mRNAs were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); Western blot was used to detect the expressions of Nrf2, HO-1, and γ-GCS proteins in pancreatic tissues.@*Results@#Compared with the control group, the levels of APN and SOD in GDM group were significantly lower (P<0.05); the levels of APN and SOD increased significantly after APS treatment, but there was no significant difference between APS-H group and Pio group; compared with the control group, the levels of TNF-α, Leptin, and MDA in the GDM group increased significantly (P<0.05); after APS treatment, the levels of TNF-α, Leptin, and MDA were significantly decreased (P<0.05), and with the increase of APS concentration, the effect of reduction was obvious, but there was no significant difference between APS-H group and Pio group; compared with the control group, the levels of FBG, FINS, insulin secretion index (IS), and insulin resistance index (IRI) in GDM group were significantly higher (P<0.05); compared with the GDM group, the levels of FBG, FINS, IS, and IRI in APS group were significantly lower, and with the increase of APS concentration, the effect of reduction was obvious, but there was no significant difference between APS-H group and Pio group; compared with the control group, the insulin sensitivity index (ISI) level in GDM group was significantly lower (P<0.05), while the level of ISI in APS group was significantly higher when treated with APS (P<0.05); the results of HE staining showed that the islet cells in the control group were regular round or oval with clear boundary; in the GDM group, the number of islets decreased significantly, while the islets atrophied without obvious boundary; after APS treatment, the number of islets increased, and the pathological damage was significantly reduced, the islet cells in Pio group showed a clear boundary after treatment; qRT-PCR showed that the expressions of Nrf2, HO-1, and γ-GCS in GDM group were significantly higher than those in control group (P<0.05), after APS treatment, the expression levels of Nrf2, HO-1, and γ-GCS decreased significantly (P<0.05), but there was no significant difference between APS-H group with Pio group; Western Blot results showed that the expressions of Nrf2, HO-1, and γ-GCS in GDM group were significantly higher than those in control group (P<0.05), after APS treatment, the levels of Nrf2, HO-1, and γ-GCS in APS group and Pio group were significantly lower than those in GDM group, but there was no significant difference between APS-H group with Pio group.@*Conclusions@#Astragalus polysaccharide can reduce insulin resistance in diabetic rats, which may play the role through Nrf2-ARE pathway.
ABSTRACT
Objective To investigate the effects of astragalus polysaccharides (APS) on insulin resistance and nuclear factor-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in gestational diabetic rats.Methods Pregnant Sprague Dawley (SD) rats were divided into normal pregnancy group (control group),model group [gestational diabetes mellitus (GDM) group],low-dose astragalus polysaccharide group (APS-L group),middle-dose astragalus polysaccharide group (APS-M group),high-dose astragalus polysaccharide group (APS-H group),pioglitazone group (Pio group).GDM rat model was established by intraperitoneal injection of streptozotocin (STZ).The levels of fasting blood glucose (FBG),fasting insulin (FINS),adiponectin (APN),tumor necrosis factor-α (TNF-α),Leptin,malondialdehyde (MDA),and superoxde dismutase (SOD) were measured before delivery and 20 days after pregnancy,then the insulin resistance index was calculated;histopathological changes of pancreas were observed by hematoxylin-eosin(HE) staining;the expressions of Nrf2,heme oxygenase-1 (HO-1),and γ-glutamyl cysteine synthase (γ-GCS)mRNAs were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR);Western blot was used to detect the expressions of Nrf2,HO-1,and γ-GCS proteins in pancreatic tissues.Results Compared with the control group,the levels of APN and SOD in GDM group were significantly lower (P ＜ 0.05);the levels of APN and SOD increased significantly after APS treatment,but there was no significant difference between APS-H group and Pio group;compared with the control group,the levels of TNF-α,Leptin,and MDA in the GDM group increased significantly (P ＜ 0.05);after APS treatment,the levels of TNF-α,Leptin,and MDA were significantly decreased (P ＜ 0.05),and with the increase of APS concentration,the effect of reduction was obvious,but there was no significant difference between APS-H group and Pio group;compared with the control group,the levels of FBG,FINS,insulin secretion index (IS),and insulin resistance index (IRI) in GDM group were significantly higher (P ＜ 0.05);compared with the GDM group,the levels of FBG,FINS,IS,and IRI in APS group were significantly lower,and with the increase of APS concentration,the effect of reduction was obvious,but there was no significant difference between APS-H group and Pio group;compared with the control group,the insulin sensitivity index (ISI) level in GDM group was significantly lower (P ＜0.05),while the level of ISI in APS group was significantly higher when treated with APS (P ＜ 0.05);the results of HE staining showed that the islet cells in the control group were regular round or oval with clear boundary;in the GDM group,the number of islets decreased significantly,while the islets atrophied without obvious boundary;after APS treatment,the number of islets increased,and the pathological damage was significantly reduced,the islet cells in Pio group showed a clear boundary after treatment;qRT-PCR showed that the expressions of Nrf2,HO-1,and γ-GCS in GDM group were significantly higher than those in control group (P ＜ 0.05),after APS treatment,the expression levels of Nrf2,HO-1,and γ-GCS decreased significantly (P ＜ 0.05),but there was no significant difference between APS-H group with Pio group;Western Blot results showed that the expressions of Nrf2,HO-1,and γ-GCS in GDM group were significantly higher than those in control group (P ＜ 0.05),after APS treatment,the levels of Nrf2,HO-1,and γ-GCS in APS group and Pio group were significantly lower than those in GDM group,but there was no significant difference between APS-H group with Pio group.Conclusions Astragalus polysaccharide can reduce insulin resistance in diabetic rats,which may play the role through Nrf2-ARE pathway.
ABSTRACT
Objective To observe the improvement effect of grape seed proanthocyanidin extract (GSPE) on myocardial function in rats with myocardial infarction and to explore its mechanism.Methods Myocardial infarction model rats were randomly divided into five groups:model group,GSPE low,middle and high group,poly ADP-ribose polymerase-1 (PARP-1) inhibitor BSI-201 group,with 15 rats in each group,and another 15 rats were as the sham operation control group.Rats in GSPE low,medium and high dose groups were administrated with 100 mg/ml GSPE,200 mg/ml GSPE and 400 mg/ml GSPE respectively;BSI-201 group was given 120 μmol/L BSI-201 of gavage,and the control group and model group were treated with equal volume of normal saline of gavage,1 times a day for 4 weeks.Doppler echocardiography was used to evaluate cardiac function in rats;myocardial infarction volume was detected by three-phenyl tetrazolium chloride (TTC) staining;hematoxylin and eosin (HE) staining was used to detect histopathological changes of myocardial tissue;terminal dexynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptosis of myocardial cells;Western blot was used to analyze the expressions of Bax,cleaved-caspase3,Bcl-2 and PAR in myocardial tissue.Results Compared with the control group,the heart rate,left ventricular end diastolic pressure,myocardial infarction area and cell apoptosis rate were significantly increased in the model group,and the mean arterial pressure and left ventricular systolic pressure were decreased significantly (P ＜ 0.05);Myocardial cells were broken and necrotic,irregular fibers arranged in the myocardium,and a large number of inflammatory cells were infiltrated;the protein expressions of Bax,cleaved-caspase3 and PAR in myocardial tissues were increased significantly (P ＜ 0.05),and the protein expression of Bcl-2 was significantly decreased (P ＜ 0.05).Compared with the model group,the heart rate,the left ventricular end diastolic pressure,myocardial infarction area and cell apoptosis rate in the GSPE low,middle and high dose groups and the BSI-201 group were significantly decreased,and the mean arterial pressure and the left ventricular systolic pressure were increased significantly (P ＜ 0.05);the degree of histopathological damage was alleviated;the expressions protein of Bax,cleaved-caspase3 and PAR in myocardial tissues were decreased significantly (P ＜ 0.05),and the protein expression of Bcl-2 was increased significantly (P ＜ 0.05).Conclusions Grape seed proanthocyanidin extract may inhibit cardiomyocyte apoptosis and improve myocardial function of rats with myocardial infarction by inhibiting PARP-1 activation.