The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphoc...The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphocyte suspension 1×106 cells/mouse through caudal vein.Grouping of testing animals:Normal control mice were healthy C57BL/6 mice without AA modeling.AA control group mice were exposed to radiation and cell transfusion and had no treatment with either CSA or XDD.CSA group mice received daily lavage with 0.027g/kg(0.1ml/10g)of CSA whereas XDD group mice received daily lavage with 19.5g/kg of XDD.The experimental result indicated CSA and XDD lavage mice had significantly higher platelet count andΔΨm than AA mice(P<0.05).Levels of Cyt C,PS and Ca2+were significantly lower in CSA and XDD groups compare with AA group.More specifically,compared to CSA group,XDD group also had lower level ofΔΨm and higher level of Cyt C and Ca2+(both P<0.05).Both CSA and XDD treatment reduced Bak and Bax levels significantly compared to AA mice.However,XDD treatment still showed higher expressions than CSA(P<0.05).CSA and XDD treatment increased the levels of Pro-apoptotic protein expressions(caspase-8,caspase-3,caspase-9).XDD showed less potent effect than CSA in increasing these protein expressions(all P<0.05).Therefore,we hypothesized XDD was possible to increase platelet number and prevent its apoptosis in immune-induced AA via the mitochondrial pathway.展开更多
Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganiza...Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.展开更多
Objective: To investigate the hepatoprotective effect of Xijiao Dihuang Decoction(犀角地黄汤,XJDHD) on lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNF-α)-induced acute liver failure(ALF)as well as the und...Objective: To investigate the hepatoprotective effect of Xijiao Dihuang Decoction(犀角地黄汤,XJDHD) on lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNF-α)-induced acute liver failure(ALF)as well as the underlying mechanism of action, and to clarify the key herbs and components of XJDHD. Methods:LPS/D-galactosamine(D-GalN) or TNF-α/D-GalN were intraperitoneally injected into C57BL/6J mice to induce ALF. Simultaneously, XJDHD or its individual herbs and components were orally administered. Survival rates, transaminase levels in serum, and hepatic histology were examined to evaluate the effects of XJDHD.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and real-time polymerase chain reaction were additionally performed to expound the mechanism underlying the anti-apoptotic activity of XJDHD. Results: Oral administration of XJDHD protected mice from lethal liver failure induced by LPS and TNF-α, with notable amelioration of liver injury in histology and a significant decrease in transaminase levels in serum. XJDHD signi?cantly inhibited apoptosis of hepatocytes and enhanced expression of the antiapoptosis genes, c-Flip, Iap1, Gadd45 b and A20(all P<0.05). In addition, Rehmannia glutinosa Libosch. was identi?ed as the key herb of XJDHD and galactose as the effective component of Rehmannia glutinosa Libosch.that protects against ALF. Conclusions: XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κB-regulated anti-apoptotic genes. Rehmannia glutinosa Libosch. may be the most effective herb of XJDHD and galactose is an active component in this protection.展开更多
Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into th...Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into the control,model,dexamethasone(DXM),golden bifid(GB)and MXDD groups using random number table,6 rats in each group.Except the control group,the other rats were developed into radiation enteritis model by exposing to a single 60Co-γray at a dose of 11 Gy.The rats in the DXM,GB and MXDD groups were treated with DXM(1.425 mg/kg),GB(0.8 g/kg)and MXDD(36.0 g/kg)for 3 days,respectively.Body weight and diarrhea condition of rats were evaluated daily.On day 3,the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected.Bacterial species annotation,alpha and beta diversities as well as composition of intestinal flora were detected and compared.The protein and mRNA expressions of interleukin 17(IL-17),retinoid-related orphan nuclear receptor gamma t(ROR-γt)and forkhead/winged helix transcription factor p3(FoxP3)were determined by Western blot and polymerase chain reaction,respectively.The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing.Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method.Results On day 1 to 3 after radiation,compared with the control group,the body weight in model group was decreased(P<0.05 or P<0.01).Compared with the model group,MXDD could alleviate weight loss and diarrhea caused by irradiation.At the phylum level,MXDD cause a significant increase in Firmicutes,and a decrease in Proteobacteria(P<0.05 or P<0.01).At the genus level,MXDD reduced the proportion of Escherichia Shigella(P<0.01).In addition,IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment(P<0.05).Besides,Firmicutes and Lactobacillus were positively correlated with FoxP3(r=0.73,0.79,respectively;P<0.01),negatively correlated with IL-17(r=0.66,0.64,respectively;P<0.01 or P<0.05)and ROR-γt(r0.73,0.81,respectively;P<0.01).Proteobacteria and Escherichia Shigella both had positive correlation with IL-17(r 0.77,0.57,respectively;P<0.01 or P<0.05)and ROR-γt(r=0.94,0.79,respectively;P<0.01)and negative correlation with FoxP3(r0.74,0.65;P<0.01).Conclusion MXDD could improve the survival status of irradiated rats by regulating the richness,diversity and composition of intestinal flora,and restoring the balance of Th17/Treg.展开更多
目的:探讨麻防犀角地黄汤对寻常性银屑病寒包火证患者皮损情况、炎症因子及中医症状评分的影响。方法:选取符合纳入标准的寻常性银屑病寒包火证患者90例,依据随机数字表随机分为麻防犀角地黄汤组、犀角地黄汤组、维A酸乳膏组,每组各30...目的:探讨麻防犀角地黄汤对寻常性银屑病寒包火证患者皮损情况、炎症因子及中医症状评分的影响。方法:选取符合纳入标准的寻常性银屑病寒包火证患者90例,依据随机数字表随机分为麻防犀角地黄汤组、犀角地黄汤组、维A酸乳膏组,每组各30例。维A酸乳膏组给予维A酸乳膏外用,犀角地黄汤组给予犀角地黄汤口服+维A酸乳膏外用,麻防犀角地黄汤组给予麻防犀角地黄汤口服+维A酸乳膏外用,均治疗30 d。观察3组患者治疗前后银屑病面积和严重程度指数(psoriasis area and severity index,PASI)评分、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)及鳞屑干燥、脱屑、瘙痒、口干中医症状评分变化情况。结果:治疗后,3组患者PASI评分,中医各症状评分及炎症因子水平均较治疗前降低(P<0.05);与维A酸乳膏组比较,麻防犀角地黄汤组和犀角地黄汤组PASI评分,中医各症状评分及炎症因子水平均降低(P<0.05);与犀角地黄汤组比较,麻防犀角地黄汤组PASI评分,中医各症状评分及炎症因子水平均降低(P<0.05)。结论:麻防犀角地黄汤治疗寻常性银屑病寒包火证疗效显著,患者皮损面积及炎症指标得到明显控制,中医临床症状明显改善。展开更多
文摘The aplastic anemia mice model was established in this study.BALB/c mice shall be treated with whole body irradiation with 60 Co-γradiation(5.5Gy,1.1Gy/min×5 min).then within 4 h,DBA/2 mice were injected lymphocyte suspension 1×106 cells/mouse through caudal vein.Grouping of testing animals:Normal control mice were healthy C57BL/6 mice without AA modeling.AA control group mice were exposed to radiation and cell transfusion and had no treatment with either CSA or XDD.CSA group mice received daily lavage with 0.027g/kg(0.1ml/10g)of CSA whereas XDD group mice received daily lavage with 19.5g/kg of XDD.The experimental result indicated CSA and XDD lavage mice had significantly higher platelet count andΔΨm than AA mice(P<0.05).Levels of Cyt C,PS and Ca2+were significantly lower in CSA and XDD groups compare with AA group.More specifically,compared to CSA group,XDD group also had lower level ofΔΨm and higher level of Cyt C and Ca2+(both P<0.05).Both CSA and XDD treatment reduced Bak and Bax levels significantly compared to AA mice.However,XDD treatment still showed higher expressions than CSA(P<0.05).CSA and XDD treatment increased the levels of Pro-apoptotic protein expressions(caspase-8,caspase-3,caspase-9).XDD showed less potent effect than CSA in increasing these protein expressions(all P<0.05).Therefore,we hypothesized XDD was possible to increase platelet number and prevent its apoptosis in immune-induced AA via the mitochondrial pathway.
基金This work was supported by funding from the National Natural Science Foundation of China(Grant Nos.81473520 and 81102697).
文摘Objective:It has been documented that ezrin/radixin/moesin(ERM)phosphorylation by the p38 mitogen-activated protein kinase(MAPK),Rho/ROCK,and protein kinase C(PKC)pathways leads to filamentous actin(F-actin)reorganization and microvascular endothelial cell hyperpermeability.In this study,we investigated the effects of Xijiao Dihuang Decoction combined with Yinqiao Powder(XDY)on influenza virus(IV)-induced F-actin restructuring and ERM phosphorylation regulated by the Rho/Rho kinase 1(ROCK),p38 MAPK,and PKC signaling pathways in pulmonary microvascular endothelial cells(PMVECs).Methods:Serum containing XDY(XDY-CS;13.8 g/kg)was acquired using standard protocols for serum pharmacology.Primary PMVECs were obtained from male Wistar rats and cultured.After adsorption of IV A(multiplicity of infection,0.01)for 1 h,medium with 20%XDY-CS was added to the PMVECs.The distributions of F-actin and phosphorylated ERM were determined by confocal microscopy,and F-actin expression was measured by flow cytometry.The expression levels of ROCK1,phosphorylated myosin phosphatase target-subunit(p-MYPT),phosphorylated MAPK kinase,phosphorylated p38(p-p38),phosphorylated PKC(p-PKC),and phosphorylated ERM(p-ERM)were determined by western blotting.Results:F-actin reorganization in IV-infected PMVECs was reversed by XDY-CS treatment,which was accompanied by reduced p-ERM production.The p-ERM protein accumulated at plasma membrane of PMVECs infected with IV,which was also inhibited by XDY-CS treatment.
基金Supported by the National Natural Science Foundation of China(No.81072766)Beijing Natural Science Foundation(No.7112066)215 Program from Beijing Public Health Bureau(No.2013-2-11)
文摘Objective: To investigate the hepatoprotective effect of Xijiao Dihuang Decoction(犀角地黄汤,XJDHD) on lipopolysaccharide(LPS)-and tumor necrosis factor alpha(TNF-α)-induced acute liver failure(ALF)as well as the underlying mechanism of action, and to clarify the key herbs and components of XJDHD. Methods:LPS/D-galactosamine(D-GalN) or TNF-α/D-GalN were intraperitoneally injected into C57BL/6J mice to induce ALF. Simultaneously, XJDHD or its individual herbs and components were orally administered. Survival rates, transaminase levels in serum, and hepatic histology were examined to evaluate the effects of XJDHD.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay and real-time polymerase chain reaction were additionally performed to expound the mechanism underlying the anti-apoptotic activity of XJDHD. Results: Oral administration of XJDHD protected mice from lethal liver failure induced by LPS and TNF-α, with notable amelioration of liver injury in histology and a significant decrease in transaminase levels in serum. XJDHD signi?cantly inhibited apoptosis of hepatocytes and enhanced expression of the antiapoptosis genes, c-Flip, Iap1, Gadd45 b and A20(all P<0.05). In addition, Rehmannia glutinosa Libosch. was identi?ed as the key herb of XJDHD and galactose as the effective component of Rehmannia glutinosa Libosch.that protects against ALF. Conclusions: XJDHD inhibits TNF-α-induced apoptosis of hepatocytes by promoting the expression of nuclear factor κB-regulated anti-apoptotic genes. Rehmannia glutinosa Libosch. may be the most effective herb of XJDHD and galactose is an active component in this protection.
文摘Objective To observe the effect of Modified Xijiao Dihuang Decoction(加味犀角地黄汤,MXDD)on rats with radiation enteritis,and explore its action mechanism.Methods Thirty female Sprague Dawley rats were divided into the control,model,dexamethasone(DXM),golden bifid(GB)and MXDD groups using random number table,6 rats in each group.Except the control group,the other rats were developed into radiation enteritis model by exposing to a single 60Co-γray at a dose of 11 Gy.The rats in the DXM,GB and MXDD groups were treated with DXM(1.425 mg/kg),GB(0.8 g/kg)and MXDD(36.0 g/kg)for 3 days,respectively.Body weight and diarrhea condition of rats were evaluated daily.On day 3,the feces of rats were collected for intestinal flora detection and the small intestinal tissues were also collected.Bacterial species annotation,alpha and beta diversities as well as composition of intestinal flora were detected and compared.The protein and mRNA expressions of interleukin 17(IL-17),retinoid-related orphan nuclear receptor gamma t(ROR-γt)and forkhead/winged helix transcription factor p3(FoxP3)were determined by Western blot and polymerase chain reaction,respectively.The abundance and diversity of intestinal flora as well as the proportion at the phylum and genus levels were assayed by 16S rRNA metagenome sequencing.Correlation between intestinal flora and Th17/Treg was analyzed by heatmap method.Results On day 1 to 3 after radiation,compared with the control group,the body weight in model group was decreased(P<0.05 or P<0.01).Compared with the model group,MXDD could alleviate weight loss and diarrhea caused by irradiation.At the phylum level,MXDD cause a significant increase in Firmicutes,and a decrease in Proteobacteria(P<0.05 or P<0.01).At the genus level,MXDD reduced the proportion of Escherichia Shigella(P<0.01).In addition,IL-17 and FoxP3 mRNA and protein expression levels were down-regulated and ROR-γt was up-regulated by MXDD treatment(P<0.05).Besides,Firmicutes and Lactobacillus were positively correlated with FoxP3(r=0.73,0.79,respectively;P<0.01),negatively correlated with IL-17(r=0.66,0.64,respectively;P<0.01 or P<0.05)and ROR-γt(r0.73,0.81,respectively;P<0.01).Proteobacteria and Escherichia Shigella both had positive correlation with IL-17(r 0.77,0.57,respectively;P<0.01 or P<0.05)and ROR-γt(r=0.94,0.79,respectively;P<0.01)and negative correlation with FoxP3(r0.74,0.65;P<0.01).Conclusion MXDD could improve the survival status of irradiated rats by regulating the richness,diversity and composition of intestinal flora,and restoring the balance of Th17/Treg.
文摘目的:探讨麻防犀角地黄汤对寻常性银屑病寒包火证患者皮损情况、炎症因子及中医症状评分的影响。方法:选取符合纳入标准的寻常性银屑病寒包火证患者90例,依据随机数字表随机分为麻防犀角地黄汤组、犀角地黄汤组、维A酸乳膏组,每组各30例。维A酸乳膏组给予维A酸乳膏外用,犀角地黄汤组给予犀角地黄汤口服+维A酸乳膏外用,麻防犀角地黄汤组给予麻防犀角地黄汤口服+维A酸乳膏外用,均治疗30 d。观察3组患者治疗前后银屑病面积和严重程度指数(psoriasis area and severity index,PASI)评分、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)及鳞屑干燥、脱屑、瘙痒、口干中医症状评分变化情况。结果:治疗后,3组患者PASI评分,中医各症状评分及炎症因子水平均较治疗前降低(P<0.05);与维A酸乳膏组比较,麻防犀角地黄汤组和犀角地黄汤组PASI评分,中医各症状评分及炎症因子水平均降低(P<0.05);与犀角地黄汤组比较,麻防犀角地黄汤组PASI评分,中医各症状评分及炎症因子水平均降低(P<0.05)。结论:麻防犀角地黄汤治疗寻常性银屑病寒包火证疗效显著,患者皮损面积及炎症指标得到明显控制,中医临床症状明显改善。
