Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic an...Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.展开更多
Objective:To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.Methods:Ma...Objective:To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.Methods:Male Sprague-Dawley rats (n =22) were divided into IBS-D (n =12) and normal control (n =10) groups.SKYD was then modeled in IBS-D rats by a combination of acetic acid enema,bondage,rectal dilation,tail stimulation,and Senna gavage.Colon tissue samples were subsequently collected and examined by Q Exactive mass spectrometry to identify differentially expressed proteins between the two groups.Results:The occurrence of SKYD/IBS-D was associated with ribosomal protein S23 (Rps23),protein phosphatase 2 catalytic subunit alpha (Pp2a),and growth factor receptor-bound protein 2 (Grb2),which are involved in the ribosome,neurotrophin signaling,and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways.Conclusion:These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation,cell growth,apoptosis,stress granule formation,immune activation,loss of epithelial cell integrity,and visceral hypersensitivity.展开更多
目的:探究温阳平喘方对脾阳虚证哮喘小鼠磷脂酰肌醇3羟激酶(phosphatidylinositol 3kinase,PI3K)、p38丝裂素活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)蛋白表达的影响。方法:将60只BALB/c雌性小鼠随机分为6组,即空...目的:探究温阳平喘方对脾阳虚证哮喘小鼠磷脂酰肌醇3羟激酶(phosphatidylinositol 3kinase,PI3K)、p38丝裂素活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)蛋白表达的影响。方法:将60只BALB/c雌性小鼠随机分为6组,即空白对照组,脾阳虚证哮喘模型组,温阳平喘方低、中、高剂量组,地塞米松组。除空白组外,其余各组小鼠连续10天制备脾阳虚证模型,之后在此基础上使用卵蛋白致敏和雾化吸入激发的方法复制哮喘模型,于激发前开始给药,两周后激发结束后取材。ELISA法检测小鼠血清中胃泌素(gastrin,GAS)浓度来判定小鼠造模结果;采用Western Blot法检测肺组织PI3K、p38MAPK蛋白表达。结果:造模结束后,模型组小鼠出现体质量减轻、呼吸频率增快、大便稀溏质软、饮食减少、活动减少、毛发欠泽,GAS浓度明显低于空白组等情况,提示造模成功。与空白组比较,模型组PI3K、p38MAPK蛋白表达水平显著升高(P<0.05);与模型组比较,温阳平喘方高剂量组PI3K、p38MAPK蛋白水平下调最为显著,且优于其他药物治疗组(P<0.05)。结论:温阳平喘方能够抑制相关的炎症因子的释放,其中以温阳平喘方高剂量组效果最优,其机制可能与升高PI3K、p38MAPK蛋白表达相关。展开更多
基金This study was supported by the National Key Research and Development Program of the Ministry of Science and Technology of the People's Republic of China(2018YFC1704304).
文摘Objective:To explore the kidney yang deficiency pattern(KYDP)in a chronic kidney disease(CKD)rat model and the mechanisms underlying the effects of Zhenwu decoction(ZWD)by conducting tran-scriptomic and metabolomic analyses.Methods:Adriamycin(ADR)combined with hydrocortisone(HC)was used to induce CKD with KYDP in rats.ADR was injected into the tail vein twice.HC was injected intramuscularly for 8 weeks.ZWD was administered by gavage for 8 weeks.The general condition was observed,24-h urine protein was detected,serum corticosterone,triiodothyronine,thyroxine,TSH,testosterone,cAMP,and cGMP levels were determined,and pathological analysis was conducted.Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes(DEGs),differentially expressed metabolites(DEMs),and differentially expressed pathways(DEPs).The core DEMs and DEGs were input to Metab-oanalyst 5.0 to identify the pathways affected by ZWD.Results:In the HC group,KYDP symptoms were observed.Compared with control group,the levels of 24-h urine protein,TSH,and cGMP significantly increased(all P<0.01),and corticosterone,triiodothyronine,thyroxine,and cAMP significantly decreased(all P<0.01)in the HC group.After ZWD intervention,the levels of above-mentioned indicators could be reversed to some extent.Pathological analysis in the HC group revealed kidney lesions.DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways.In the ZWD group,differences in biosynthesis of unsat-urated fatty acids and butanoate metabolism were observed.The following pathways were significantly affected by ZWD:arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.Conclusion:ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism,valine,leucine,and isoleucine biosynthesis,linoleic acid metabolism,and alpha-linolenic acid metabolism.
基金grants from the National Natural Science Foundation of China(no.81403389)the Beijing Key Laboratory of Functional Gastrointestinal Disorders Diagnosis and Treatment of Traditional Chinese Medicine(no.BZ0374).
文摘Objective:To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.Methods:Male Sprague-Dawley rats (n =22) were divided into IBS-D (n =12) and normal control (n =10) groups.SKYD was then modeled in IBS-D rats by a combination of acetic acid enema,bondage,rectal dilation,tail stimulation,and Senna gavage.Colon tissue samples were subsequently collected and examined by Q Exactive mass spectrometry to identify differentially expressed proteins between the two groups.Results:The occurrence of SKYD/IBS-D was associated with ribosomal protein S23 (Rps23),protein phosphatase 2 catalytic subunit alpha (Pp2a),and growth factor receptor-bound protein 2 (Grb2),which are involved in the ribosome,neurotrophin signaling,and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways.Conclusion:These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation,cell growth,apoptosis,stress granule formation,immune activation,loss of epithelial cell integrity,and visceral hypersensitivity.
基金This work was supported by the Project of Hunan Provincial Natural Science Foundation of China(湖南省自然科学基金项目,No.2022JJ40301)Fund Project of Hunan Province Education Office(湖南省教育厅科学研究项目,No.21B0369)Scientific Fund Project of Hunan University of Chinese Medicine(湖南中医药大学科研基金项目,No.2021XJJJ013).
