目的采用网络药理学方法探究中药赤芍的主要活性成分及其治疗IgA肾病(IgA Nephropathy,IgAN)的作用机制。方法以口服生物利用度(Oralbioavailability,OB)≥30%和类药性(Drug like,DL)≥0.18为标准,从中药系统药理学数据库分析平台(Tradi...目的采用网络药理学方法探究中药赤芍的主要活性成分及其治疗IgA肾病(IgA Nephropathy,IgAN)的作用机制。方法以口服生物利用度(Oralbioavailability,OB)≥30%和类药性(Drug like,DL)≥0.18为标准,从中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)中筛选出赤芍的活性成分、作用靶点,采用Cytoscape 3.7.2软件构建活性成分-作用靶点网络图。在GeneCards、DrugBank、DisGeNET、GAD等数据库中寻找与IgAN有关的所有靶点,将赤芍作用靶点与IgAN相关靶点取交集,筛选出赤芍治疗IgAN的活性成分及作用靶点。借助Cytoscape3.7.2软件,构建赤芍治疗IgAN的活性成分-作用靶点网络,选出关键化合物。通过STRING数据库构建靶蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络,并选出核心靶点。在基因表达综合(Gene Expression Omnibus,GEO)数据库,下载基因矩阵与平台数据文件,运用Perl脚本和R语言分析验证关键靶点可行性。使用DAVID数据库分析平台,对靶点基因进行GO富集分析和KEGG信号通路富集分析。结果从赤芍中筛选获得13个有效活性成分,80个作用靶点,与IgAN有关的有效活性成分11个,核心靶点35个。利用GEO数据库中GSE93798芯片与平台数据,分析验证前10个关键靶点,其中FOS、JUN为赤芍治疗IgAN的显著性差异基因。KEGG信号通路主要涉及乙型肝炎(Hepatitis B)通路、IL-17信号通路、TNF信号通路等,这些通路可能是赤芍防治IgAN的作用途径。结论初步研究了赤芍治疗IgAN的药效物质基础及其可能的作用机制,赤芍可以通过多个靶点、多条通路来发挥治疗IgAN。展开更多
目的通过荟萃分析评价火把花根片治疗慢性肾小球肾炎的疗效及安全性。方法计算机检索PubMed、Embase、Web of science、Cochrane library、CNKI、Wan Fang、CBM、VIP等数据库,搜集火把花根片治疗慢性肾小球肾炎的随机对照试验,检索时限...目的通过荟萃分析评价火把花根片治疗慢性肾小球肾炎的疗效及安全性。方法计算机检索PubMed、Embase、Web of science、Cochrane library、CNKI、Wan Fang、CBM、VIP等数据库,搜集火把花根片治疗慢性肾小球肾炎的随机对照试验,检索时限均从建库至2022年9月。按Cochrane协作网质量评价标准评价,提取有效数据,采用Revman 5.4软件进行荟萃分析,分析火把花根片对慢性肾小球肾炎的临床疗效。结果最终共纳入8篇文献,共703例患者。荟萃分析结果显示:与对照组相比,火把花根片治疗组在提高临床有效率(RR=1.24,95%CI:1.04~1.48,P=0.02)、降低24h尿蛋白(MD=-1.51,95%CI:-2.47~-0.55,P=0.002)及血尿素氮(MD=-0.53,95%CI:-0.71~-0.34,P<0.00001)、改善血清白蛋白(MD=3.48,95%CI:2.72~4.25,P<0.00001)、减少尿红细胞(MD=-11.46,95%CI:-18.29~-4.64,P=0.001)等方面均有优势,但在降低血肌酐及不良反应方面与对照组差异均无统计学意义(均P>0.05)。结论火把花根片对慢性肾小球肾炎有良好的疗效,但仍需更多大样本、多中心、高质量的随机对照试验数据支持。展开更多
目的探讨银杏叶提取物EGB761对糖尿病肾病(DKD)小鼠肾小管损伤及内质网应激的影响。方法将50只C57BL/6N小鼠随机分为正常组、DKD模型组、DKD+EGB761组(36 mg·kg-1)以及DKD+4-苯基丁酸(4-PBA)组(1 g·kg-1)。通过高脂饲料联合...目的探讨银杏叶提取物EGB761对糖尿病肾病(DKD)小鼠肾小管损伤及内质网应激的影响。方法将50只C57BL/6N小鼠随机分为正常组、DKD模型组、DKD+EGB761组(36 mg·kg-1)以及DKD+4-苯基丁酸(4-PBA)组(1 g·kg-1)。通过高脂饲料联合腹腔注射链脲佐菌素(STZ)制备糖尿病小鼠模型,糖尿病模型复制成功并继续高脂饲料喂养8周后检测各组尿蛋白,阳性者给药8周,给药期间观察各组小鼠一般情况。给药8周后检测血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白(24 h Pro)、空腹血糖(FBG)、肾脏肥大指数;HE染色、Masson染色、PAS染色观察各组小鼠肾脏病理改变;透射电镜观察肾小球及肾小管超微结构;ELLSA法检测各组小鼠肾小管损伤标志物尿β2-微球蛋白(β2-MG)、视黄醇结合蛋白4(RBP4)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的表达;以免疫组化、蛋白免疫印迹法(Western blot)、实时荧光定量聚合酶链式反应(Realtime-PCR)检测肾组织内质网应激标志物GRP78、ATF6的表达。结果与正常组比,DKD模型组精神状态较差、反应迟钝、多饮多食多尿症状明显,Scr、BUN、24 h Pro、FBG、肾脏肥大指数均明显升高(P<0.01),肾脏病理损伤加重,尿β2-MG、RBP4、NGAL明显升高(P<0.01),肾组织GRP78、ATF6的表达明显升高(P<0.01)。与DKD模型组相比,DKD+EGB761组精神状态、反应情况及多饮多食多尿症状好转,Scr、BUN、24 h Pro、FBG水平均明显降低(P<0.01),肾脏肥大指数明显降低(P<0.05),肾脏病理损伤明显改善,尿β2-MG、RBP4、NGAL表达降低(P<0.05,P<0.01),肾组织GRP78、ATF6蛋白的表达降低(P<0.05,P<0.01)。结论银杏叶提取物EGB761可以改善DKD小鼠肾功能,减少蛋白尿,减轻肾小管损伤,其作用机制可能与抑制内质网应激相关。展开更多
OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:nor...OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:normal,model,Tongluo Digui decoction(high,medium,and low dose)and valsartan.Streptozotocin was injected intraperitoneally to replicate the diabetic animal model.After 8 weeks,proteinuria was evaluated to establish the diabetic nephropathy model.Treatments were administered daily via the intragastric route.At 16 weeks after gavage,we determined 24 h urine protein concentration,and blood glucose,serum creatinine,and urea nitrogen concentrations.Then,rats were sacrificed,and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli,including glomerular podocytes by transmission electron microscopy.Western blot analysis was used to determine the expression of nephrin,podocin,p62,beclin-1,LC3Ⅱ/Ⅰ,and p-m TOR/m TOR protein in kidney tissues.RESULTS:Compared with the model group,Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration,and blood glucose,hemoglobin A1 c,serum creatinine,urea nitrogen concentrations,total serum protein and albumin.Concurrently,mesangial mesenteric broadening and fusion of foot processes were reduced,the glomerular basement membrane was not significantly thickened,and the number of podocytes and the number of autophagosomes in the podocytes was increased.Further,expression of nephrin,podocin,LC3Ⅱ,and beclin-1 protein in kidney tissue was up-regulated,while expression of p62 protein was down-regulated and m TOR phosphorylation was inhibited.CONCLUSION:Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting m TOR phosphorylation,thereby increasing autophagy to protect podocytes and reducing proteinuria.展开更多
文摘目的采用网络药理学方法探究中药赤芍的主要活性成分及其治疗IgA肾病(IgA Nephropathy,IgAN)的作用机制。方法以口服生物利用度(Oralbioavailability,OB)≥30%和类药性(Drug like,DL)≥0.18为标准,从中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)中筛选出赤芍的活性成分、作用靶点,采用Cytoscape 3.7.2软件构建活性成分-作用靶点网络图。在GeneCards、DrugBank、DisGeNET、GAD等数据库中寻找与IgAN有关的所有靶点,将赤芍作用靶点与IgAN相关靶点取交集,筛选出赤芍治疗IgAN的活性成分及作用靶点。借助Cytoscape3.7.2软件,构建赤芍治疗IgAN的活性成分-作用靶点网络,选出关键化合物。通过STRING数据库构建靶蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络,并选出核心靶点。在基因表达综合(Gene Expression Omnibus,GEO)数据库,下载基因矩阵与平台数据文件,运用Perl脚本和R语言分析验证关键靶点可行性。使用DAVID数据库分析平台,对靶点基因进行GO富集分析和KEGG信号通路富集分析。结果从赤芍中筛选获得13个有效活性成分,80个作用靶点,与IgAN有关的有效活性成分11个,核心靶点35个。利用GEO数据库中GSE93798芯片与平台数据,分析验证前10个关键靶点,其中FOS、JUN为赤芍治疗IgAN的显著性差异基因。KEGG信号通路主要涉及乙型肝炎(Hepatitis B)通路、IL-17信号通路、TNF信号通路等,这些通路可能是赤芍防治IgAN的作用途径。结论初步研究了赤芍治疗IgAN的药效物质基础及其可能的作用机制,赤芍可以通过多个靶点、多条通路来发挥治疗IgAN。
文摘目的探讨银杏叶提取物EGB761对糖尿病肾病(DKD)小鼠肾小管损伤及内质网应激的影响。方法将50只C57BL/6N小鼠随机分为正常组、DKD模型组、DKD+EGB761组(36 mg·kg-1)以及DKD+4-苯基丁酸(4-PBA)组(1 g·kg-1)。通过高脂饲料联合腹腔注射链脲佐菌素(STZ)制备糖尿病小鼠模型,糖尿病模型复制成功并继续高脂饲料喂养8周后检测各组尿蛋白,阳性者给药8周,给药期间观察各组小鼠一般情况。给药8周后检测血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白(24 h Pro)、空腹血糖(FBG)、肾脏肥大指数;HE染色、Masson染色、PAS染色观察各组小鼠肾脏病理改变;透射电镜观察肾小球及肾小管超微结构;ELLSA法检测各组小鼠肾小管损伤标志物尿β2-微球蛋白(β2-MG)、视黄醇结合蛋白4(RBP4)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的表达;以免疫组化、蛋白免疫印迹法(Western blot)、实时荧光定量聚合酶链式反应(Realtime-PCR)检测肾组织内质网应激标志物GRP78、ATF6的表达。结果与正常组比,DKD模型组精神状态较差、反应迟钝、多饮多食多尿症状明显,Scr、BUN、24 h Pro、FBG、肾脏肥大指数均明显升高(P<0.01),肾脏病理损伤加重,尿β2-MG、RBP4、NGAL明显升高(P<0.01),肾组织GRP78、ATF6的表达明显升高(P<0.01)。与DKD模型组相比,DKD+EGB761组精神状态、反应情况及多饮多食多尿症状好转,Scr、BUN、24 h Pro、FBG水平均明显降低(P<0.01),肾脏肥大指数明显降低(P<0.05),肾脏病理损伤明显改善,尿β2-MG、RBP4、NGAL表达降低(P<0.05,P<0.01),肾组织GRP78、ATF6蛋白的表达降低(P<0.05,P<0.01)。结论银杏叶提取物EGB761可以改善DKD小鼠肾功能,减少蛋白尿,减轻肾小管损伤,其作用机制可能与抑制内质网应激相关。
基金Supported by the funds of Key Scientific Research Project of Colleges and Universities in Henan Province in 2017(Explore the Mechanism of Huoxue Tongluo Decoction in Preventing and Treating Diabetic Nephropathy from the Regulation of Podocyte Autophagy by Mtor Signal Pathway,No.17A360003)the Research Project of National TCM Clinical Research Base(Project Number:2019jdzx068+9 种基金Project Name:Study on the Effect of Tongluo Digui Decoction on Circadian Rhythm of Diabetic Nephropathy Based on Lncrna-mrna Chip Technology)the Special Research Project of TCM In Henan Province(Project Number:2019zybj17Project Name:Study on the Mechanism of Tongluo Digui Decoction in the Treatment of Diabetic Kidney Disease by Regulating the Pyroptosis of Podocyte through Autophagy-related Molecular Pathways)Henan Province Key R&D and Promotion Special(Science and Technology)Project(Project Number:202102310505Project Name:Study on the Mechanism Of Tongluo Digui Decoction in the Treatment of Diabetic Nephropathy Based on Autophagy Regulating Renal Tubular Epithelial Cell Pyroptosis)Henan Province Key R&D and Promotion Special(Science and Technology)Project(Project Number:202102310171Project Name:to Explore the Mechanism of Tongluo Digui Decoction on Improving Non-dipper Blood Pressure In Diabetic Nephropathy Based on Circadian Rhythm)a Sub-station Project of the Inheritance Studio of Famous Old Chinese Medicine Experts Across the CountryTCM Top Talent Training Project of Henan ProvinceNational TCM Innovational Core Talent Training Project。
文摘OBJECTIVE:To investigate the effects of Tongluo Digui decoction on renal injury and streptozotocin-induced podocyte autophagy in diabetic rats.METHODS:Male Sprague-Dawley rats were randomly divided into six groups:normal,model,Tongluo Digui decoction(high,medium,and low dose)and valsartan.Streptozotocin was injected intraperitoneally to replicate the diabetic animal model.After 8 weeks,proteinuria was evaluated to establish the diabetic nephropathy model.Treatments were administered daily via the intragastric route.At 16 weeks after gavage,we determined 24 h urine protein concentration,and blood glucose,serum creatinine,and urea nitrogen concentrations.Then,rats were sacrificed,and kidneys were harvested and stained with periodic acid-Schiff to evaluate the pathological changes in glomeruli,including glomerular podocytes by transmission electron microscopy.Western blot analysis was used to determine the expression of nephrin,podocin,p62,beclin-1,LC3Ⅱ/Ⅰ,and p-m TOR/m TOR protein in kidney tissues.RESULTS:Compared with the model group,Tongluo Digui decoction was associated with decreases in 24 h urine protein concentration,and blood glucose,hemoglobin A1 c,serum creatinine,urea nitrogen concentrations,total serum protein and albumin.Concurrently,mesangial mesenteric broadening and fusion of foot processes were reduced,the glomerular basement membrane was not significantly thickened,and the number of podocytes and the number of autophagosomes in the podocytes was increased.Further,expression of nephrin,podocin,LC3Ⅱ,and beclin-1 protein in kidney tissue was up-regulated,while expression of p62 protein was down-regulated and m TOR phosphorylation was inhibited.CONCLUSION:Tongluo Digui decoction may inhibit the progression of diabetic nephropathy by inhibiting m TOR phosphorylation,thereby increasing autophagy to protect podocytes and reducing proteinuria.
