AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five gr...AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosupp展开更多
目的:系统评价雷公藤多苷联合来氟米特治疗类风湿关节炎的疗效和安全性。方法:计算机检索Cochrane library、Web of Science、Pubmed、国家知识基础设施数据库(CNKI)、中国生物医学文献数据库(CBM)、中国学术期刊数据库(CSPD)和中文科...目的:系统评价雷公藤多苷联合来氟米特治疗类风湿关节炎的疗效和安全性。方法:计算机检索Cochrane library、Web of Science、Pubmed、国家知识基础设施数据库(CNKI)、中国生物医学文献数据库(CBM)、中国学术期刊数据库(CSPD)和中文科技期刊数据库(CCD),检索时限为建库起至2020年8月14日,收集雷公藤多苷联合来氟米特治疗类风湿关节炎的临床试验资料,采用Cochrane5.1.0系统评价手册进行质量评估,采用RevMan5.3软件进行数据分析。结果:共纳入随机对照试验13项,含类风湿关节炎患者1004例,其中观察组503例,对照组501例。Meta分析结果显示,晨僵时间(SMD=-1.55,95%CI为-1.87~-1.23)、(SMD=-2.29,95%CI为-3.46~-1.12)、关节疼痛数(SMD=-0.94,95%CI为-1.40~-0.49)、关节肿胀数(SMD=-0.78,95%CI为-1.52~-0.04)、红细胞沉降率(SMD=-1.75,95%CI为-2.38~-1.13)、C反应蛋白(SMD=-2.23,95%CI为-2.96~-1.51)、类风湿因子(SMD=-2.97,95%CI为-4.22~-1.72)、免疫球蛋白G(SMD=-0.58,95%CI为-1.10~-0.06)、白细胞介素-1(SMD=-0.84,95%CI为-1.20~-0.49)、白细胞介素-6(SMD=-4.08,95%CI为-4.86~-3.30)、肿瘤坏死因子-α(SMD=-3.24,95%CI为-3.92~-2.56)、(SMD=-0.94,95%CI为-1.30~-0.57)和可溶性细胞间黏附分子-1(SMD=-0.53,95%CI为-0.96~-0.10),观察组均显著低于对照组;临床总有效率观察组明显优于对照组(OR=4.12,95%CI为2.74~6.18);休息痛、免疫球蛋白A、免疫球蛋白M、白细胞介素-10和不良反应发生率观察组与对照组差异无统计学意义。结论:雷公藤多苷联合来氟米特治疗类风湿关节炎可提高患者的临床总有效率,改善类风湿关节炎患者相关的各项体征及症状,并且具有良好的安全性,值得临床推广应用;但由于受收录文献质量的限制和临床异质性的影响,研究结果尚需临床实践验证。展开更多
基金Supported by the National Natural Science Foundation of China,No.81672422,No.81600506,and No.81702757Open Project in State Key Laboratory for Diagnosis and Treatment of Infectious Disease,No.2015KF03+4 种基金National S&T Major Project of China,No.2018ZX10301201Natural Science Foundation of Zhejiang Province,No.LY15H160033China Postdoctoral Science Foundation,No.2017464Zhejiang Province Health Department Program,No.2014KYB081,and No.2017KY322Academician Jieshou Li Mucosal Barrier Fund,No.201208
文摘AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosupp
文摘目的:系统评价雷公藤多苷联合来氟米特治疗类风湿关节炎的疗效和安全性。方法:计算机检索Cochrane library、Web of Science、Pubmed、国家知识基础设施数据库(CNKI)、中国生物医学文献数据库(CBM)、中国学术期刊数据库(CSPD)和中文科技期刊数据库(CCD),检索时限为建库起至2020年8月14日,收集雷公藤多苷联合来氟米特治疗类风湿关节炎的临床试验资料,采用Cochrane5.1.0系统评价手册进行质量评估,采用RevMan5.3软件进行数据分析。结果:共纳入随机对照试验13项,含类风湿关节炎患者1004例,其中观察组503例,对照组501例。Meta分析结果显示,晨僵时间(SMD=-1.55,95%CI为-1.87~-1.23)、(SMD=-2.29,95%CI为-3.46~-1.12)、关节疼痛数(SMD=-0.94,95%CI为-1.40~-0.49)、关节肿胀数(SMD=-0.78,95%CI为-1.52~-0.04)、红细胞沉降率(SMD=-1.75,95%CI为-2.38~-1.13)、C反应蛋白(SMD=-2.23,95%CI为-2.96~-1.51)、类风湿因子(SMD=-2.97,95%CI为-4.22~-1.72)、免疫球蛋白G(SMD=-0.58,95%CI为-1.10~-0.06)、白细胞介素-1(SMD=-0.84,95%CI为-1.20~-0.49)、白细胞介素-6(SMD=-4.08,95%CI为-4.86~-3.30)、肿瘤坏死因子-α(SMD=-3.24,95%CI为-3.92~-2.56)、(SMD=-0.94,95%CI为-1.30~-0.57)和可溶性细胞间黏附分子-1(SMD=-0.53,95%CI为-0.96~-0.10),观察组均显著低于对照组;临床总有效率观察组明显优于对照组(OR=4.12,95%CI为2.74~6.18);休息痛、免疫球蛋白A、免疫球蛋白M、白细胞介素-10和不良反应发生率观察组与对照组差异无统计学意义。结论:雷公藤多苷联合来氟米特治疗类风湿关节炎可提高患者的临床总有效率,改善类风湿关节炎患者相关的各项体征及症状,并且具有良好的安全性,值得临床推广应用;但由于受收录文献质量的限制和临床异质性的影响,研究结果尚需临床实践验证。
