BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therap...BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.展开更多
Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided ...Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.展开更多
目的:探究芪黄固肾通络方对糖尿病肾病(DKD)小鼠的治疗效果,及其通过过氧化酶增殖激活受体γ(PPAR-γ)调控脂代谢和自噬对肾脏纤维化和足细胞的影响。方法:将C57BL6/J小鼠分为正常组、模型组和芪黄固肾通络方低、中、高剂量组,用链脲佐...目的:探究芪黄固肾通络方对糖尿病肾病(DKD)小鼠的治疗效果,及其通过过氧化酶增殖激活受体γ(PPAR-γ)调控脂代谢和自噬对肾脏纤维化和足细胞的影响。方法:将C57BL6/J小鼠分为正常组、模型组和芪黄固肾通络方低、中、高剂量组,用链脲佐菌素(STZ)诱导DKD模型。检测血糖、血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白(24 h pro)等指标,观察肾脏超微结构和病理变化,检测PPAR-γ、微管相关蛋白1A/1B-轻链3(LC-3)、p62蛋白(SQSTM-1/p62)等蛋白表达。体外培养小鼠肾足细胞(MPC-5),用含药血清干预,检测相关蛋白表达和脂质积累。结果:模型组小鼠表现出明显的肾脏损伤,足突蛋白(Podocin)、肾病蛋白(Nephrin)表达下降,血糖、尿蛋白、Scr、BUN上升,PPAR-γ、p62等蛋白表达增加,LC3、苄氯素1(Beclin-1)下降,脂质沉积增多。芪黄固肾通络方能显著改善上述指标,降低PPAR-γ、p62表达,增加LC-3、Beclin-1表达,减少脂质沉积。体外实验显示,芪黄固肾通络方含药血清上调Beclin-1、LC3表达,下调p62、PPAR-γ表达,减轻脂质积累。结论:芪黄固肾通络方可能通过下调PPAR-γ,增强自噬,减轻DKD小鼠肾脏纤维化,保护足细胞,对DKD具有治疗作用。展开更多
基金Supported by the Scientific Foundation of Administration of Traditional Chinese Medicine of Hebei Province,China,No.2023257.
文摘BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.
基金Construction Project for Famous Doctors of Traditional Chinese Medicine of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine(No.[2019]18)。
文摘Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.
文摘目的:探究芪黄固肾通络方对糖尿病肾病(DKD)小鼠的治疗效果,及其通过过氧化酶增殖激活受体γ(PPAR-γ)调控脂代谢和自噬对肾脏纤维化和足细胞的影响。方法:将C57BL6/J小鼠分为正常组、模型组和芪黄固肾通络方低、中、高剂量组,用链脲佐菌素(STZ)诱导DKD模型。检测血糖、血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白(24 h pro)等指标,观察肾脏超微结构和病理变化,检测PPAR-γ、微管相关蛋白1A/1B-轻链3(LC-3)、p62蛋白(SQSTM-1/p62)等蛋白表达。体外培养小鼠肾足细胞(MPC-5),用含药血清干预,检测相关蛋白表达和脂质积累。结果:模型组小鼠表现出明显的肾脏损伤,足突蛋白(Podocin)、肾病蛋白(Nephrin)表达下降,血糖、尿蛋白、Scr、BUN上升,PPAR-γ、p62等蛋白表达增加,LC3、苄氯素1(Beclin-1)下降,脂质沉积增多。芪黄固肾通络方能显著改善上述指标,降低PPAR-γ、p62表达,增加LC-3、Beclin-1表达,减少脂质沉积。体外实验显示,芪黄固肾通络方含药血清上调Beclin-1、LC3表达,下调p62、PPAR-γ表达,减轻脂质积累。结论:芪黄固肾通络方可能通过下调PPAR-γ,增强自噬,减轻DKD小鼠肾脏纤维化,保护足细胞,对DKD具有治疗作用。
