Objective:To investigate the cardioprotective effect of Yiqi Huoxue granule(YQHXG)in the regulation of autophagy in rats induced with myocardial infarction(MI).Methods:An acute MI animal model was established by ligat...Objective:To investigate the cardioprotective effect of Yiqi Huoxue granule(YQHXG)in the regulation of autophagy in rats induced with myocardial infarction(MI).Methods:An acute MI animal model was established by ligation of the left anterior descending branch of the coronary artery in Sprague-Dawley rats.Besides,20 rats received sham operation were classified into a control group.The remaining 59 rats were randomly divided into MI model group(n=19),YQHXG group(n=20),and perindopril group(n=20).Relevant indicators on days 7 and 28 were observed in each group.Left ventricular function was determined by echocardiography.The structure and morphology of mitochondria,and the number of autophagic vesicles,were observed by transmission electron microscopy.The mRNA and protein expression levels of LC3,FUNDC1,Beclin-1,and BNIP3 were examined in the tissue of the MI marginal area.Results:Compared with the MI model group,YQHXG showed obvious improvements in cardiac functions.Observing the microscopic morphology of the heart tissue,myocardial tissue damage attenuated,autophagic signs of autophagosomes and autolysosomes reduced,vacuolization in mitochondria mitigated,and mitochondria arranged in order.YQHXG could reduce the degree of tissue lesion after MI and regulate the expression of autophagy-related molecules at different stages.On Day 7,YQHXG significantly downregulated the expression of Fundc1,Becn1,Bnip3 mRNA and reduced the levels of FUNDC1,Beclin-1,BNIP3,and LC3 B proteins expression(all P<.001).On Day 28,YQHXG could upregulate the expression of Becn1,Fundc1 and Bnip3 mRNA and increased the levels of the corresponding proteins expression(all P<.001).Besides,it also increased LC3 B protein expression level(P=.0344).Conclusion:YQHXG regulated the expression of mitochondrial autophagy-related factors in myocardial tissue and mitochondrial autophagic activity at different stages to protect the heart following MI.展开更多
Objective:To investigate the effects of Qishen Yiqi Keli(QSYQ;Astragalus Salvia Granules to Benefit the Qi)on ROS scavenging and inhibition of NADPH oxidase in an effort to identify new natural antioxidants.Methods:A ...Objective:To investigate the effects of Qishen Yiqi Keli(QSYQ;Astragalus Salvia Granules to Benefit the Qi)on ROS scavenging and inhibition of NADPH oxidase in an effort to identify new natural antioxidants.Methods:A total of 23 representative components in QSYQ were investigated,their effects on hydrogen peroxide induced ROS were assayed by dichlorofluorescein assay.Lucigenin chemiluminescence was adopted to test the effect on NADPH oxidase activity in H9C2 cardiomyocyte cells,and pyrogallol autoxidation was adopted to test the superoxide scavenging capacity.Results:Nine compounds in QSYQ could significantly inhibited H2O2-induced ROS increase compared with the model group(P<.05),including tanshinone I,salvianolic acid A,danshinone IIA,and cryptotanshinone from salvia root,luteolin from salvia root,harpagoside,harpagide,and angoroside C from scrophularia root.Nine compounds in QSYQ could significantly inhibited the production ofO2in H9C2 cell.Tanshinone I showed a lowest IC50 value 0.07 mM,the other including salvianolic acid A,cryptotanshinone,and salvianolic acid B,luteolin,isochlorogenic acid C,astragaloside IV,and glycyrrhetinic acid.Licochalcone A inhibited the autoxidation of pyrogallol at a low concentration,and tanshinone I showed no significant inhibitory effect from 2 mM to 20 mM.Conclusion:QSYQ had significant effects on ROS scavenging and inhibition of NADPH oxidase.Tanshinone I and salvianolic acid A are potential NADPH oxidase inhibitors.展开更多
Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the pro...Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.展开更多
Objective: To observe the clinical effect of Yiqi Huoxue (益气活血, YQHX) herbs in treating the patients with chronic cor pulmonale and to explore its mechanism by determining the relationship of oxida-tion/antioxidat...Objective: To observe the clinical effect of Yiqi Huoxue (益气活血, YQHX) herbs in treating the patients with chronic cor pulmonale and to explore its mechanism by determining the relationship of oxida-tion/antioxidation system and how such herbs change on the function of endothelial cells and platelets. Methods: Fifty-eight patients were divided into two groups: conventional therapy group (control group, 28 patients) and convention plus YQHX herbs group (treated group, 30 patients). The control group received conventional management. The treated group were treated with YQHX 150 ml, twice a day, plus the conventional treatment, and the clinical efficacy was recorded. The lipid peroxidation (LPO), superoxide dismutase (SOD), ot-granule membrane protein (GMP140), partial pressure of arterial oxygen (PaO2), partial pressure of carbon dioxide in artery (PaCO2) and circulating endothelial cells (CEC) were measured respectively before and after treatment, and the relationship between various parameters were analyzed. The results were compared with those of 10 healthy subjects got at the same period. Results: (1) The effective rate and PaO2 of the treated group was higher than that of the control group and there were no difference in PaCO2 between the two groups. (2) The levels of LPO, GMP140, CEC in all the patients before therapy were significantly higher than those of the healthy group, and there were marked decrease in the levels of those after treatment (all P<0. 01). On the contrary, the levels of SOD in all the patients before therapy were markedly lower than those in the healthy subjects and increased after treatment, P<0. 01. (3) The increase of SOD in the treated group was significantly more obvious than that of the control group. In the treated group, the decrease of LPO, GMP140, CEC were markedly more obvious than those in the control group (all P<0. 01). (4) The number of CEC, as well as GMP140, was negatively correlated to PaO2(P<0.01) and SOD (P< 0. 01), which was positively correlated to LPO (P<0. 01). There was a positive correlation between CEC and GMP140 (P<0.05). Conclusion: YQHX herbs in treating chronic cor pulmonale proved to be effective by balancing the oxidation and antioxidation, protecting the pulmonary endothelial cells and activated platelets and helpful in treating respiratory failure.展开更多
OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method ...OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.展开更多
基金the National Natural Science Foundation of China(81473552).
文摘Objective:To investigate the cardioprotective effect of Yiqi Huoxue granule(YQHXG)in the regulation of autophagy in rats induced with myocardial infarction(MI).Methods:An acute MI animal model was established by ligation of the left anterior descending branch of the coronary artery in Sprague-Dawley rats.Besides,20 rats received sham operation were classified into a control group.The remaining 59 rats were randomly divided into MI model group(n=19),YQHXG group(n=20),and perindopril group(n=20).Relevant indicators on days 7 and 28 were observed in each group.Left ventricular function was determined by echocardiography.The structure and morphology of mitochondria,and the number of autophagic vesicles,were observed by transmission electron microscopy.The mRNA and protein expression levels of LC3,FUNDC1,Beclin-1,and BNIP3 were examined in the tissue of the MI marginal area.Results:Compared with the MI model group,YQHXG showed obvious improvements in cardiac functions.Observing the microscopic morphology of the heart tissue,myocardial tissue damage attenuated,autophagic signs of autophagosomes and autolysosomes reduced,vacuolization in mitochondria mitigated,and mitochondria arranged in order.YQHXG could reduce the degree of tissue lesion after MI and regulate the expression of autophagy-related molecules at different stages.On Day 7,YQHXG significantly downregulated the expression of Fundc1,Becn1,Bnip3 mRNA and reduced the levels of FUNDC1,Beclin-1,BNIP3,and LC3 B proteins expression(all P<.001).On Day 28,YQHXG could upregulate the expression of Becn1,Fundc1 and Bnip3 mRNA and increased the levels of the corresponding proteins expression(all P<.001).Besides,it also increased LC3 B protein expression level(P=.0344).Conclusion:YQHXG regulated the expression of mitochondrial autophagy-related factors in myocardial tissue and mitochondrial autophagic activity at different stages to protect the heart following MI.
基金a grant from The National Natural Science Fund(No.81403319)Creation for Significant New Drugs Project of China(No.2012ZX09103-201-011)。
文摘Objective:To investigate the effects of Qishen Yiqi Keli(QSYQ;Astragalus Salvia Granules to Benefit the Qi)on ROS scavenging and inhibition of NADPH oxidase in an effort to identify new natural antioxidants.Methods:A total of 23 representative components in QSYQ were investigated,their effects on hydrogen peroxide induced ROS were assayed by dichlorofluorescein assay.Lucigenin chemiluminescence was adopted to test the effect on NADPH oxidase activity in H9C2 cardiomyocyte cells,and pyrogallol autoxidation was adopted to test the superoxide scavenging capacity.Results:Nine compounds in QSYQ could significantly inhibited H2O2-induced ROS increase compared with the model group(P<.05),including tanshinone I,salvianolic acid A,danshinone IIA,and cryptotanshinone from salvia root,luteolin from salvia root,harpagoside,harpagide,and angoroside C from scrophularia root.Nine compounds in QSYQ could significantly inhibited the production ofO2in H9C2 cell.Tanshinone I showed a lowest IC50 value 0.07 mM,the other including salvianolic acid A,cryptotanshinone,and salvianolic acid B,luteolin,isochlorogenic acid C,astragaloside IV,and glycyrrhetinic acid.Licochalcone A inhibited the autoxidation of pyrogallol at a low concentration,and tanshinone I showed no significant inhibitory effect from 2 mM to 20 mM.Conclusion:QSYQ had significant effects on ROS scavenging and inhibition of NADPH oxidase.Tanshinone I and salvianolic acid A are potential NADPH oxidase inhibitors.
基金This research was supported and funded by the National Natural Science Foundation of China(No.81373541).
文摘Objective:To investigate how Yiqi Yangyin and Huatan Quyu granule (YYHO) improves skeletal muscle insulin resistance in a type 2 diabetic rat model and to discover whether the molecular mechanism is related to the promotion of the AMPK/SIRT/PGC-1α signalling pathway.Methods:Rats were randomly divided into 4 groups:the normal group,the model group,the YYHQ granule group,and the pioglitazone group.The type 2 diabetic rat model was established by feeding a high-fat diet for 5 weeks along with a single intraperitoneal injection of 30 mg/kg streptozotocin (STZ).After modelling successfully,the appropriate drug was intragastrically administered to diabetic rats for 2 weeks,once per day.The YYHQ granule group was given a dose of 4.8 g/kg body weight per day,the pioglitazone group was given a dose of 1.35 mg/kg body weight per day.The doses for both groups were equivalent to the clinical equivalent dose based on a previous study.Other groups were gavaged with the same amount of saline water.Body weight,food intake,water intake,urine volume and grip strength were recorded weekly.The fasting blood glucose(FBG) was determined weekly using blood glucose test strips.The related glucose and lipid metabolism indexes,e.g.,fasting insulin (Fins),glycated haemoglobin (GHb),HOMA-IR,ISI,triglycerides (TG),total cholesterol (TC),high-density lipoprotein cholesterol (HDL-C),low-density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA),were determined using biochemical method.The mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK),peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α),carnitine palmitoyl transterase-1 (CPT-1),Sirtuin 1 (SIRT1),and Sirtuin 3 (SIRT3) were assessed using quantitative real-time PCR (qRT-PCR).The protein expression levels of creatine kinase (CK),Ca2+ ATPase,α-Actin,AMPK,PGC-1α and CPT-1 were determined using enzyme-linked immunosorbent assay method (ELISA).Results:Body weight decreased significantly (P <.01),food intake,water intake and urine volume increased significantly (P <.01),and grip strength decreased significantly (P <.01) in the model group compared with the normal group.The levels of FBG,Fins,GHb and HOMA-IR increased significantly (P <.01),and the ISI decreased significantly (P <.01) in the model group.The levels of TG,TC,LDL-C and FFA increased significantly (P <.05 or P <.01),and the level of HDL-C decreased significantly (P <.05) in the model group.These changes were reversed after treatment with YYHQ granule or pioglitazone.Compared with the model group,the YYHQ granule and pioglitazone groups significantly improve body weight,water intake and urine volume (P <.05 or P <.01),however,both treatments had no significant effect on food intake (P >.05).The levels of FBG,Fins,GHb,HOMA-IR and ISI were improved significantly (P <.01) and the levels of TG,TC and LDL-C were improved significantly (P <.05 or P <.01),however,both treatments had no significant effect on the levels of HDL-C and FFA (P >.05).Further results indicated that YYHQ granule significantly decreased the mRNA expression of AMPK,PGC-1α,CPT-1,SIRT1 and SIRT3 in skeletal muscle (P <.01) and the pioglitazone group showed similar effects;moreover,the protein expression levels of CK,Ca2+ATPase,α-Actin,AMPK,PGC-1α and CPT-1 in skeletal muscle significantly decreased (P <.01),however,pioglitazone had no significant effect on CK and α-Actin (P >.05).Conclusion:The possible molecular mechanism of YYHQ granule improving skeletal muscle insulin resistance in a type 2 diabetic rat model may be related to the stimulation of energy metabolism in skeletal muscle via the AMPK/SIRT/PGC-1α signalling pathway.
文摘Objective: To observe the clinical effect of Yiqi Huoxue (益气活血, YQHX) herbs in treating the patients with chronic cor pulmonale and to explore its mechanism by determining the relationship of oxida-tion/antioxidation system and how such herbs change on the function of endothelial cells and platelets. Methods: Fifty-eight patients were divided into two groups: conventional therapy group (control group, 28 patients) and convention plus YQHX herbs group (treated group, 30 patients). The control group received conventional management. The treated group were treated with YQHX 150 ml, twice a day, plus the conventional treatment, and the clinical efficacy was recorded. The lipid peroxidation (LPO), superoxide dismutase (SOD), ot-granule membrane protein (GMP140), partial pressure of arterial oxygen (PaO2), partial pressure of carbon dioxide in artery (PaCO2) and circulating endothelial cells (CEC) were measured respectively before and after treatment, and the relationship between various parameters were analyzed. The results were compared with those of 10 healthy subjects got at the same period. Results: (1) The effective rate and PaO2 of the treated group was higher than that of the control group and there were no difference in PaCO2 between the two groups. (2) The levels of LPO, GMP140, CEC in all the patients before therapy were significantly higher than those of the healthy group, and there were marked decrease in the levels of those after treatment (all P<0. 01). On the contrary, the levels of SOD in all the patients before therapy were markedly lower than those in the healthy subjects and increased after treatment, P<0. 01. (3) The increase of SOD in the treated group was significantly more obvious than that of the control group. In the treated group, the decrease of LPO, GMP140, CEC were markedly more obvious than those in the control group (all P<0. 01). (4) The number of CEC, as well as GMP140, was negatively correlated to PaO2(P<0.01) and SOD (P< 0. 01), which was positively correlated to LPO (P<0. 01). There was a positive correlation between CEC and GMP140 (P<0.05). Conclusion: YQHX herbs in treating chronic cor pulmonale proved to be effective by balancing the oxidation and antioxidation, protecting the pulmonary endothelial cells and activated platelets and helpful in treating respiratory failure.
基金National Natural Science Foundation of China:Action Mechanism of Buzhong Yiqi Decoction in Treating Hashimoto's Thyroiditis based on transforming growth factor β/Smad Signaling Pathway and the Balance between Treg and Th17 Cells(No.81973855)。
文摘OBJECTIVE:To observe the effects of Buzhong Yiqi granule(补中益气颗粒)on thyroid function and ovarian function in rats with experimental autoimmune thyroiditis(EAT).METHODS:EAT model was replicate by using the method of mixing and injecting porcine thyroglobulin with Freund's adjuvant and high iodine.Rats were randomly divided into normal control(NC)group,EAT model(EAT)group,selenium yeast(PC)group,low dose Buzhong Yiqi(BZYQ-L)group,medium dose Buzhong Yiqi(BZYQ-M)group and high dose Buzhong Yiqi(BZYQ-H)group.After two months of drug intervention according to dosage,enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of free triiodothyronine(FT3),free thyroxine(FT4),thyroid-stimulating hormone(TSH),antithyroid peroxidase antibody(TPOAb),thyroglobulin antibody(TGAb)in peripheral blood of rats.The pathological changes of rat thyroid tissues were observed under light microscope with HE staining;ELISA was used to determine estradiol(E2),follicle-stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),antimüllerian hormone(AMH),and the pathological changes of rat ovarian tissues were observed under light microscope with hematoxylin and eosin staining.RESULTS:Compared with the NC group,BZYQ granule improved the thyroid and ovarian tissue morphology,and the levels of TPOAb,TGAb and TSH in the model group rats significantly increased(P<0.05),the thyroid tissue was severely destroyed,the levels of E2,FSH,LH,T,AMH significantly increased(P<0.05),and the ovary exhibited polycystic changes;Compared with the model group,TSH level in the BZYQ-L group rats decreased(P<0.05),FSH,T,AMH levels decreased(P<0.05),in the BZYQ-M group TPOAb,TSH levels decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),BZYQ-H group TPOAb,TGAb,TSH levels significantly decreased(P<0.05),FSH,LH,T,AMH levels significantly decreased(P<0.05),with the greatest improvement and significantly better than selenium yeast group(P<0.05).CONCLUSIONS:BZYQ granule could regulate the thyroid function of EAT rats,reduce thyroid antibody titers,then act on the ovarian function,regulate hormone disorders,and alleviate the pathological damage of rat's ovarian tissues.The effect of high dose Buzhong Yiqi granule is the best.