[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided i...[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.展开更多
BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-z...BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.展开更多
文摘[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.
基金Supported by Natural Science Foundation of Sichuan Province,No.2022NSFSC0738Basic Research Funds for Central Universities,No.2682022ZTPY038Tibet Autonomous Region Science and Technology Planning Project,No.XZ2022RH001.
文摘BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.
