AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: no...AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachlodde group (CCh)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCh in olive oil twice a week for 12 wk. The CCh group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (y-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCh group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P〈0.05). QGHXF high dose group was better than XCH group in ALT (615± 190 vs 867± 115),and AST(1972 ± 366 vs 2777 ± 608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4±3.13, 13.79±2.26 and 10.07± 1.14, higher than model group, 6.58±1.04 (P〈 0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.展开更多
AIM: To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction (JHD) on cytokine secretion pathway in rat liver induced by lipopolysaccharide (LPS). METHODS: Twenty-four male ...AIM: To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction (JHD) on cytokine secretion pathway in rat liver induced by lipopolysaccharide (LPS). METHODS: Twenty-four male SD rats were divided into normal group (n = 4), model group (n = 10) and JHD group (n = 10) randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin (H.E.) staining. Tumor necrosis factor alpha (TNF-α) in serum were assayed by enzyme linked immunosorbent assay (ELISA). The protein expression of TNF-α, phosphorylated inhibit-κB (p-κB) and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 (IL-6), CD14, toll-like receptor 2 (TLR2) and TLR4 in liver were assayed by real-time RT-PCR.RESULTS: Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α (31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05), protein expression of CD68 (1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05), p-IκB (0.01 ±0.01 vs 2.07 + 0.83, P 〈 0.01) and TNF-α (0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01) in liver and mRNA expression of TNF-α (1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01), IL-6 (4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01) and TLR2 (1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01) in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA (1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05) was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION: JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.展开更多
Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the interve...Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention. Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegmdampness syndrome and the effect of Wen Dan Decoction. Results (1) There were 3 242 methylation differential loci in dietinduced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that "offactory receptor activity" and others were enriched. The possible signal pathways involved were "Olfactory transduction""Tuberculosis""Systemic lupus erythematosus" and "Ribosome".(2) After the intervention of Wen Dan Decoction in obesity with phlegmdampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as "Metabolic pathways".(3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes. Conclusions The phlegm-dampness syndrome of obesityinduced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.展开更多
The accuracy of hard core attractive Yukawa (HCAY) potential and adhesivehard sphere (AH) potential in representing the structure factor of short range square well potentialand Asakura and Oosawa (AO) depletion potent...The accuracy of hard core attractive Yukawa (HCAY) potential and adhesivehard sphere (AH) potential in representing the structure factor of short range square well potentialand Asakura and Oosawa (AO) depletion potential is examined by comparing theoretical predictionswith the existing simulation data and the present numerical results from the non-linear optimizedrandom phase approximation closure for Ornstein—Zernike equation. For the case of square-well (SW)potential, it is shown that the structure factor of HCAY potential based on a recently proposedsemi-analytical expression for the radial distribution function can describe the structure factor ofSW potential with reduced well width λ ≤ 2 only if the reduced contact potential βε_(sw) ≤0.25, while the analytical expression for the structure factor of AH potential under Percus-Yevick(PY) approximation completely fails for the case of λ 】 1.2. For the case of AO depletionpotential, the domain of validity of both HCAY potential and AH potential is complementary. With theabove analysis and considering the solid-liquid transition of the AH potential with an adhesiveparameter τ below 1.31 cannot be predicted by modified weighted density approximation, the roleplayed by the HCAY potential about the mapping manipulation should not be ignored.展开更多
Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets ...Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets of the TCM were retrieved using the systematic pharmacological analysis platform TCMSP,and the gene name of each target protein was obtained from the UniProtKB network platform.The targets of RA were queried through the CTD database.The protein–protein interaction network was constructed in the STRING database,and the network visualization analysis was performed in Cytoscape.The Gene Ontology and Kyoto Gene and Genomic Encyclopedia pathways enrichment analyses of key target proteins were performed using the DAVID data platform.Results:A total of 472 drug active ingredients were screened from the TCMSP database.Seventy-five disease targets from the CTD database were screened.The compound-target network map contained further screened out 98 components and corresponding 75 targets.The key compounds included quercetin and kaempferol.The key targets were prostaglandin G/H synthase 2 and nitric oxide synthase 2.The protein-protein interaction network consisted of 75 proteins,of which 37 were key proteins,including tumor protein 53,JUN and interleukin-6.There were 260 Gene Ontology entries,of which 246 were biological processes.Fifty-five Kyoto Gene and Genomic Encyclopedia pathways were enriched,mainly the cancer pathway,NOD-like receptor signaling pathway,and Toll-like receptor signaling pathway,which are involved in the action mechanism of FHD.Conclusion:The results of this study preliminarily verified the basic pharmacological action mechanism of FHD in the treatment of RA,laying a foundation for elucidating its mechanism of action.展开更多
Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'phys...Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.展开更多
OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by...OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD(18 g·kg-1 collagen was observ·d-1) for 90 days.Myocardialed by mallory trichrome staining. Capillary density was quantified by using Factor rentially expⅧre immunohistochemical staining.Diffessed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling(DGE)system. Real-time quantitative polymerase chain reaction detecting system(q PCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes.RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2,monocyte chemotactic protein 1, neuropeptide Y,arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment.CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.展开更多
Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebr...Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.展开更多
基金Supported by Shanghai Rising-Star program, No. 03QMH1410
文摘AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism. METHODS: Wistar rats were divided into three groups at random: normal control group (12), micro-amount carbon tetrachlodde group (CCh)(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCh in olive oil twice a week for 12 wk. The CCh group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (y-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCh group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P〈0.05). QGHXF high dose group was better than XCH group in ALT (615± 190 vs 867± 115),and AST(1972 ± 366 vs 2777 ± 608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4±3.13, 13.79±2.26 and 10.07± 1.14, higher than model group, 6.58±1.04 (P〈 0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group. CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.
基金Supported by The National Natural Science Foundation of China, No.30371818Shanghai Rising-Star Program, No. 07QA14052Shanghai Leading Academic Discipline Project, Y0302 and Shanghai Educational Development Foundation, No. 2007CG56
文摘AIM: To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction (JHD) on cytokine secretion pathway in rat liver induced by lipopolysaccharide (LPS). METHODS: Twenty-four male SD rats were divided into normal group (n = 4), model group (n = 10) and JHD group (n = 10) randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 μg/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylineosin (H.E.) staining. Tumor necrosis factor alpha (TNF-α) in serum were assayed by enzyme linked immunosorbent assay (ELISA). The protein expression of TNF-α, phosphorylated inhibit-κB (p-κB) and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-α, interleukin-6 (IL-6), CD14, toll-like receptor 2 (TLR2) and TLR4 in liver were assayed by real-time RT-PCR.RESULTS: Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-α (31.35 ± 6.06 vs 12225.40 ± 9007.03, P 〈 0.05), protein expression of CD68 (1.13 ± 0.49 vs 3.36 ±1.69, P 〈 0.05), p-IκB (0.01 ±0.01 vs 2.07 + 0.83, P 〈 0.01) and TNF-α (0.27 ± 0.13 vs 1.29 ± 0.37, P 〈 0.01) in liver and mRNA expression of TNF-α (1.96 ± 2.23 vs 21.45 ±6.00, P 〈 0.01), IL-6 (4.80 ± 6.42 vs 193.50 ± 36.36, P 〈 0.01) and TLR2 (1.44 ± 0.62 vs 4.16 ± 0.08, P 〈 0.01) in liver were also increased significantly. These pathological changes were all improved in .1HD group. On the other hand, TLR4 mRNA (1.22 ± 0.30 vs 0.50 ± 0.15, P 〈 0.05) was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION: JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IκB and endotoxin receptor TLR2.
基金the funding support from the National Natural Science Youth Foundation of China: Effect of Wen Dan Decoction on gene promoter methylations related to fat metabolism (No. 81302907)
文摘Objective To observe the characteristics of gene methylation in obese rats with phlegm-dampness syndrome induced by the high-fat diet, and to study the effect of Wen Dan Decoction on gene methylation after the intervention. Methods Methylation sites of genes were detected by the MeDIP-seq method. Bioinformatics method was used to analyze the gene methylation characteristics of obesity with phlegmdampness syndrome and the effect of Wen Dan Decoction. Results (1) There were 3 242 methylation differential loci in dietinduced obesity with phlegm-dampness syndrome, of which 1 243 were down-regulated and 1 999 were up-regulated, involving 1 579 differential genes. GO analysis showed that "offactory receptor activity" and others were enriched. The possible signal pathways involved were "Olfactory transduction""Tuberculosis""Systemic lupus erythematosus" and "Ribosome".(2) After the intervention of Wen Dan Decoction in obesity with phlegmdampness syndrome, 4 046 different methylation loci were obtained, including 1 067 down-regulated loci and 2 979 up-regulated loci, involving 2 068 genes. GO analysis showed that "offactory receptor activity" and others were enriched. These genes involved seven signaling pathways, such as "Metabolic pathways".(3) Between diet-induced obesity with phlegm-dampness syndrome and Wen Dan Decoction intervening obesity with the phlegm-dampness syndrome, 582 common genes of methylation differential genes were obtained. After the intervention of Wen Dan Decoction, the number of GO enrichment items was more than that of obesity with phlegm-dampness syndrome, and even the same GO enrichment items involved more genes. Conclusions The phlegm-dampness syndrome of obesityinduced by diet had the characteristics of gene methylation changes, and the intervention of Wen Dan Decoction could also affect the status of gene methylation. The genes affected by Wen Dan Decoction were closely related to the methylation gene of phlegm-dampness syndrome of obesity-induced by diet but covered a wider range.
文摘The accuracy of hard core attractive Yukawa (HCAY) potential and adhesivehard sphere (AH) potential in representing the structure factor of short range square well potentialand Asakura and Oosawa (AO) depletion potential is examined by comparing theoretical predictionswith the existing simulation data and the present numerical results from the non-linear optimizedrandom phase approximation closure for Ornstein—Zernike equation. For the case of square-well (SW)potential, it is shown that the structure factor of HCAY potential based on a recently proposedsemi-analytical expression for the radial distribution function can describe the structure factor ofSW potential with reduced well width λ ≤ 2 only if the reduced contact potential βε_(sw) ≤0.25, while the analytical expression for the structure factor of AH potential under Percus-Yevick(PY) approximation completely fails for the case of λ 】 1.2. For the case of AO depletionpotential, the domain of validity of both HCAY potential and AH potential is complementary. With theabove analysis and considering the solid-liquid transition of the AH potential with an adhesiveparameter τ below 1.31 cannot be predicted by modified weighted density approximation, the roleplayed by the HCAY potential about the mapping manipulation should not be ignored.
文摘Objective:To explore the pharmacological action mechanism of Fang Ji Huang Qi decoction(FHD)in the treatment of rheumatoid arthritis(RA)by network pharmacology.Methods:The chemical compositions and functional targets of the TCM were retrieved using the systematic pharmacological analysis platform TCMSP,and the gene name of each target protein was obtained from the UniProtKB network platform.The targets of RA were queried through the CTD database.The protein–protein interaction network was constructed in the STRING database,and the network visualization analysis was performed in Cytoscape.The Gene Ontology and Kyoto Gene and Genomic Encyclopedia pathways enrichment analyses of key target proteins were performed using the DAVID data platform.Results:A total of 472 drug active ingredients were screened from the TCMSP database.Seventy-five disease targets from the CTD database were screened.The compound-target network map contained further screened out 98 components and corresponding 75 targets.The key compounds included quercetin and kaempferol.The key targets were prostaglandin G/H synthase 2 and nitric oxide synthase 2.The protein-protein interaction network consisted of 75 proteins,of which 37 were key proteins,including tumor protein 53,JUN and interleukin-6.There were 260 Gene Ontology entries,of which 246 were biological processes.Fifty-five Kyoto Gene and Genomic Encyclopedia pathways were enriched,mainly the cancer pathway,NOD-like receptor signaling pathway,and Toll-like receptor signaling pathway,which are involved in the action mechanism of FHD.Conclusion:The results of this study preliminarily verified the basic pharmacological action mechanism of FHD in the treatment of RA,laying a foundation for elucidating its mechanism of action.
基金supported by the Scientific Research Project of Guangdong Province Traditional Chinese Medicine Bureau(20201229)and China Postdoctoral Science Foundation Project(2021M701438).
文摘Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.
基金Supported by National Natural Science Foundation of China Project:Studies of Qi-Supplementing Therapy Promoting Angiogenesis after Myocardial Infarction by Simulation of Angptl6 Pathway in NK Cells(No.81302892)Effects of Polyamine-derived Aldehyde Load Injury in Long-term Prognosis after Myocardial Infarction Ventricular Remodeling,and the Modulation Mechanism of Buyanghuanwu Decoction(No.81173459)+4 种基金Studies of the Role of 5-LOX/Cys LT2R in Left Ventricular Remodeling after Myocardial Infarction and the Pharmacological Mechanisms of BYHWD(No.81373575)Effects of Hsp20 on Ventricular Remodeling after Myocardial Infarction,and the Modulation Mechanism of Buyanghuanwu decoction(No.81202841)Guangdong Natural Science Foundation Project:Studies of Qi-Supplementing Therapy Promoting Angiogenesis after Myocardial Infarction by Simulation of Angptl6 Pathway in NK Cells(No.S2013040016226)Studies of the role of 5-LOX/Cys LT2R in Left Ventricular Remodeling after Myocardial Infarction and the Pharmacological Mechanisms of BYHWD(No.S2013010014777)Specialized Research Fund for the Doctoral Program of Higher Education Project:Effects of Polyamine-derived Aldehyde Load Injury in Long-term Prognosis after Myocardial Infarction Ventricular Remodeling,and the Modulation Mechanism of Buyanghuanwu decoction(No.20124433110019)
文摘OBJECTIVE: To investigate the effect of Buyanghuanwu decoction(BYHWD) on gene expression in ventricular remodeling post-myocardial infarction in rats.METHODS: Animal models of myocardial infarction were established by permanent ligation of the left anterior descending coronary artery. Echocardiography measurements were performed after the treatment of BYHWD(18 g·kg-1 collagen was observ·d-1) for 90 days.Myocardialed by mallory trichrome staining. Capillary density was quantified by using Factor rentially expⅧre immunohistochemical staining.Diffessed genes were explored by a short-read sequencing technology combined with a tag-based digital gene expression profiling(DGE)system. Real-time quantitative polymerase chain reaction detecting system(q PCR) was used to validate the sequencing results. After assembling the gene information from Sham, model and BYHWD groups, we constructed three DGE libraries based on each group. The sequencing of three libraries generated 66 000-73 000 unique tags, which were mapped to reference sequences for annotation of expressed genes.RESULTS: Among them, 511 and 352 differentially expressed genes were found in comparison with sham/model and model/BYHWD, respectively. Fifty-five genes exhibited reversed direction of gene expression differences between Sham/Model and Model/BYHWD groups. We found that transforming growth factor beta receptor-1, junctophilin-2,monocyte chemotactic protein 1, neuropeptide Y,arachidonate 5-Lipoxygenase, arachidonate 15-Lipoxygenase were significantly modulated, which suggested the involvement of these genes in BYHWD treatment.CONCLUSION: The DGE profiling data provide comprehensive gene expression information at the transcriptional level that could facilitate our understanding of the pharmacological mechanisms of BYHWD in ventricular remodeling post-myocardial infarction.
基金supported by Henan Province Higher Learning Institution Outstanding Scientific Research Talent Innovation Engineering Project (2007KYCX007)Henan Province Outstanding Youth Project (08100510015)
文摘Objective:To explore the mechanism of Buyang Huanwu Tang (补阳还五汤 Decoction Invigorating Yang for Recuperation) combined with bone marrow mesenchymal stem cells (MSCs) transplantation in protecting nerves of cerebral ischemic injury. Methods: Local cerebral ischemia-reperfusion rat model was established with modified Zea-Longa thread-occlusion method, and MSCs were injected into the caudal vein, and Buyang Huanwu Tang(补阳还五汤)was administrated. Vascular endothelial growth factor (VEGF) and Ki-67 expression in the ischemic side of the brain in the cerebral ischemic-reperfusion rat were detected with immuno-histochemical staining method. Results: VEGF and Ki-67 expressions were significantly up-regulated in the MSCs group and the combination group, with significant differences as compared with the model group and the sham operation group (P<0.05), and with the most strongest effect in the combination group. Conclusion: Buyang Huanwu Tang(补阳还五汤)combined with MSCs transplantation repairs the injured blood vessels and lesion tissues possibly by up-regulation of VEGF and Ki-67 expression.