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
目的观察肾病Ⅰ、Ⅱ、Ⅲ号方分阶段治疗难治性肾病综合征的临床疗效。方法将76例难治性肾病综合征患者随机分为2组,对照组给予常规西医治疗,治疗组在对照组治疗基础上分阶段予以肾病Ⅰ、Ⅱ、Ⅲ号方治疗。观察2组治疗前后24h尿蛋白定量...目的观察肾病Ⅰ、Ⅱ、Ⅲ号方分阶段治疗难治性肾病综合征的临床疗效。方法将76例难治性肾病综合征患者随机分为2组,对照组给予常规西医治疗,治疗组在对照组治疗基础上分阶段予以肾病Ⅰ、Ⅱ、Ⅲ号方治疗。观察2组治疗前后24h尿蛋白定量、血清白蛋白(ALB)、血胆固醇(TC)、三酰甘油(TG)、血尿素氮(BUN)、血肌酐(SCr)、血常规及水肿、乏力、腹胀、腰酸证候积分变化情况,统计2组疾病疗效及疾病缓解的时间、中医证候疗效及感染、肝损害情况。结果治疗后24 h 2组尿蛋白定量、ALB、TC、TG、BUN、SCr均较治疗前明显改善(P均<0.05),且治疗组24 h尿蛋白定量、ALB、TC、TG改善情况均明显优于对照组(P均<0.05);治疗后2组BUN、SCr比较差异无统计学意义。治疗后2组各项中医证候积分均较治疗前明显改善(P均<0.05),且治疗组改善情况明显优于对照组(P均<0.05)。治疗组疾病缓解率和中医证候总有效率均明显高于对照组(P均<0.05),感染和肝损害发生率均明显低于对照组(P均<0.05)。结论肾病Ⅰ、Ⅱ、Ⅲ号方联合常规西医治疗难治性肾病综合征疗效好,且可减少感染及肝损害的发生。展开更多
Diabetic kidney disease(DKD)is the most common complication of diabetes mellitus(DM).Qianjin Wenwu decoction(QWD),a well-known traditional Korean medicine,has been used for the treatment of DKD,with satisfactory thera...Diabetic kidney disease(DKD)is the most common complication of diabetes mellitus(DM).Qianjin Wenwu decoction(QWD),a well-known traditional Korean medicine,has been used for the treatment of DKD,with satisfactory therapeutic effects.This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD.The results demonstrated that a total of 13 active components in five types were found in QwD,including flavonoids,flavonoid glycosides,phenylpropionic acids,saponins,coumarins,and lignins.Two key proteins,TGF-β1 and TIMP-1,were identified as the target proteins through molecular docking.Furthermore,QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction(UUO).Hematoxylin&eosin(H&E)and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice.We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF-βl in DKD treatment.These findings explain the underlying mechanism of QWD for the treatment of DKD,and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.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.
文摘目的观察肾病Ⅰ、Ⅱ、Ⅲ号方分阶段治疗难治性肾病综合征的临床疗效。方法将76例难治性肾病综合征患者随机分为2组,对照组给予常规西医治疗,治疗组在对照组治疗基础上分阶段予以肾病Ⅰ、Ⅱ、Ⅲ号方治疗。观察2组治疗前后24h尿蛋白定量、血清白蛋白(ALB)、血胆固醇(TC)、三酰甘油(TG)、血尿素氮(BUN)、血肌酐(SCr)、血常规及水肿、乏力、腹胀、腰酸证候积分变化情况,统计2组疾病疗效及疾病缓解的时间、中医证候疗效及感染、肝损害情况。结果治疗后24 h 2组尿蛋白定量、ALB、TC、TG、BUN、SCr均较治疗前明显改善(P均<0.05),且治疗组24 h尿蛋白定量、ALB、TC、TG改善情况均明显优于对照组(P均<0.05);治疗后2组BUN、SCr比较差异无统计学意义。治疗后2组各项中医证候积分均较治疗前明显改善(P均<0.05),且治疗组改善情况明显优于对照组(P均<0.05)。治疗组疾病缓解率和中医证候总有效率均明显高于对照组(P均<0.05),感染和肝损害发生率均明显低于对照组(P均<0.05)。结论肾病Ⅰ、Ⅱ、Ⅲ号方联合常规西医治疗难治性肾病综合征疗效好,且可减少感染及肝损害的发生。
基金supported by the National Natural Science Foundation of China(No.81660709)Jilin Scientific and Technological Agency Development Program(No.20190304065YY).
文摘Diabetic kidney disease(DKD)is the most common complication of diabetes mellitus(DM).Qianjin Wenwu decoction(QWD),a well-known traditional Korean medicine,has been used for the treatment of DKD,with satisfactory therapeutic effects.This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD.The results demonstrated that a total of 13 active components in five types were found in QwD,including flavonoids,flavonoid glycosides,phenylpropionic acids,saponins,coumarins,and lignins.Two key proteins,TGF-β1 and TIMP-1,were identified as the target proteins through molecular docking.Furthermore,QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction(UUO).Hematoxylin&eosin(H&E)and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice.We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF-βl in DKD treatment.These findings explain the underlying mechanism of QWD for the treatment of DKD,and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
