目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO...目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO)等数据库检索强直性脊柱炎相关芯片,利用R语言分析得到差异表达基因。借助人类基因数据库(GeneCards)、疾病基因数据库(DisGeNET)、孟德尔遗传综合数据库(online Mendelian inheritance in man,OMIM)、疾病数据库(MalaCards)、遗传药理学和药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)等数据库对强直性脊柱炎已知靶基因进行检索与筛选,与差异表达基因去重取并集,对强直性脊柱炎的疾病靶基因进行预测。运用中药药理学平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库对羌活胜湿汤七味中药的主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的蛋白质互作(protein-protein interaction,PPI)网络,通过基因注释(database for annotation,visualization and integrated discovery,David)数据库对药物-疾病关键靶基因进行生物通路及富集分析。最终将羌活胜湿汤中主要有效成分与关键靶基因进行分子对接。结果:羌活胜湿汤有效成分-靶基因网络图包含176个有效成分,相对应靶点137个;GEO数据库获得差异表达基因704个,通过疾病数据库检索与强直性脊柱炎发生发展相关的已知疾病靶标1323个,合并去重后共获得1950个已知疾病靶基因;最终获得映射靶基因46个,关键靶基因13个。羌活胜湿汤主要通过肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、氯霉素乙酰转移酶基因(chloramphnicol acetyltransferase,CAT)、雌激素受体1(estrogen receptor 1,ESR1)、环加氧酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等作用于脂多糖介导的信号通路、一氧化氮生物合成过程的正调控、血管生成等生物过程及FoxO信号通路、炎症性肠病、各促炎因子相关信号通路等多个信号通路。分子对接结果显示:羌活胜湿汤中主要有效成分在与关键靶基因对接过程中均进入了活性位点,具有很强的结合能力。结论:应用生物信息学和分子对接技术方法可揭示羌活胜湿汤治疗强直性脊柱炎的潜在作用机制,具有较高的置信度和参考价值,为中药组方在治疗强直性脊柱炎方面提供了新的方向与思路。展开更多
During the period of the Japanese occupation,ordinary civil servants were the main force keeping the puppet municipal government of Tianjin functioning.In the first years of the occupation,the puppet municipal governm...During the period of the Japanese occupation,ordinary civil servants were the main force keeping the puppet municipal government of Tianjin functioning.In the first years of the occupation,the puppet municipal government mainly hired former civil servants who had served under the Nanjing National Government.After the situation was stable,the puppet municipal government also recruited civil servants by civil service examinations.The ranks of civil servants and the rules and regulations they observed were basically the same as those of the former National Government.Most ordinary civil servants came from the Beijing-Tianjin-Hebei region,and were relatively young and well educated.They mainly relied on their salaries for their livelihood.For the first three years of the Japanese occupation they lived comfortably,because of their relatively high and stable incomes and the slow rate of inflation.After that,inflation soared,but their salaries did not increase correspondingly,therefore the living conditions of civil servants declined constantly.The Japanese puppet government exercised strict control over civil servants,physically and psychologically,and forced them to receive enslaving education.In short,they were in a distorted and struggling state both in their material life and their spiritual world.展开更多
文摘目的:利用生物信息学及分子对接技术探究羌活胜湿汤治疗强直性脊柱炎的作用机制。方法:通过美国国家生物技术信息中心数据库(national center for biotechnology information,NCBI)、高通量基因表达数据库(gene expression omnibus,GEO)等数据库检索强直性脊柱炎相关芯片,利用R语言分析得到差异表达基因。借助人类基因数据库(GeneCards)、疾病基因数据库(DisGeNET)、孟德尔遗传综合数据库(online Mendelian inheritance in man,OMIM)、疾病数据库(MalaCards)、遗传药理学和药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)等数据库对强直性脊柱炎已知靶基因进行检索与筛选,与差异表达基因去重取并集,对强直性脊柱炎的疾病靶基因进行预测。运用中药药理学平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库对羌活胜湿汤七味中药的主要有效成分及作用靶基因进行筛选和挖掘,构建药物与疾病映射靶基因的蛋白质互作(protein-protein interaction,PPI)网络,通过基因注释(database for annotation,visualization and integrated discovery,David)数据库对药物-疾病关键靶基因进行生物通路及富集分析。最终将羌活胜湿汤中主要有效成分与关键靶基因进行分子对接。结果:羌活胜湿汤有效成分-靶基因网络图包含176个有效成分,相对应靶点137个;GEO数据库获得差异表达基因704个,通过疾病数据库检索与强直性脊柱炎发生发展相关的已知疾病靶标1323个,合并去重后共获得1950个已知疾病靶基因;最终获得映射靶基因46个,关键靶基因13个。羌活胜湿汤主要通过肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素6(interleukin-6,IL-6)、白细胞介素1β(interleukin-1β,IL-1β)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、氯霉素乙酰转移酶基因(chloramphnicol acetyltransferase,CAT)、雌激素受体1(estrogen receptor 1,ESR1)、环加氧酶2(prostaglandin-endoperoxide synthase 2,PTGS2)等作用于脂多糖介导的信号通路、一氧化氮生物合成过程的正调控、血管生成等生物过程及FoxO信号通路、炎症性肠病、各促炎因子相关信号通路等多个信号通路。分子对接结果显示:羌活胜湿汤中主要有效成分在与关键靶基因对接过程中均进入了活性位点,具有很强的结合能力。结论:应用生物信息学和分子对接技术方法可揭示羌活胜湿汤治疗强直性脊柱炎的潜在作用机制,具有较高的置信度和参考价值,为中药组方在治疗强直性脊柱炎方面提供了新的方向与思路。
文摘During the period of the Japanese occupation,ordinary civil servants were the main force keeping the puppet municipal government of Tianjin functioning.In the first years of the occupation,the puppet municipal government mainly hired former civil servants who had served under the Nanjing National Government.After the situation was stable,the puppet municipal government also recruited civil servants by civil service examinations.The ranks of civil servants and the rules and regulations they observed were basically the same as those of the former National Government.Most ordinary civil servants came from the Beijing-Tianjin-Hebei region,and were relatively young and well educated.They mainly relied on their salaries for their livelihood.For the first three years of the Japanese occupation they lived comfortably,because of their relatively high and stable incomes and the slow rate of inflation.After that,inflation soared,but their salaries did not increase correspondingly,therefore the living conditions of civil servants declined constantly.The Japanese puppet government exercised strict control over civil servants,physically and psychologically,and forced them to receive enslaving education.In short,they were in a distorted and struggling state both in their material life and their spiritual world.
