Objective： To observe the effect of Safflor Yellow （SY） Injection on acute lung injury （ALl） induced by lipopolysaccharide （LPS） in mice. Methods： Seventy-two mice were divided into six groups： control （sali...Objective： To observe the effect of Safflor Yellow （SY） Injection on acute lung injury （ALl） induced by lipopolysaccharide （LPS） in mice. Methods： Seventy-two mice were divided into six groups： control （saline ＋ saline）; LPS （LPS ＋ saline）; SY Injection [LPS ＋ SY （10, 20 or 40 mg/kg, intravenously）] and anisodamine （AD） （LPS ＋ AD）. Thirty minutes after SY or AD administration, 15 mg/kg LPS was given intraperitoneally. All animals were sacrificed 4 h after LPS injection. Arterial blood gas and lung water content index （LWCI） were measured. Lung tissue myeloperoxidase （MPO） activity was assayed, mRNA expression of inflammatory cytokines was assayed by reverse-transcription polymerase chain reaction. Lung morphological and nuclear factor （NF）- K B p65-positive cell changes were observed by HE and immunohistochemical staining, p38 mitogen-activated protein kinase （MAPK） phosphorylation was observed by Western blotting. Results： After LPS administration, all animals displayed increased arterial carbon dioxide partial pressure （PaCO2） and decreased arterial oxygen partial pressure （PaO2）, arterial oxygen saturation （SO2）, HCOs concentration and pH, and increased LWCI, MPO activity, interleukin （IL）-I β, IL-6 and tumor necrosis factor （TNF）-ot mRNA expression, NF-K B p65 positive staining and p38 MAPK activation compared with normal controls （all P〈0.01）. SY Injection significantly mitigated the LPS-induced increase in arterial PaCO2 and the decreases in arterial PaO2, SO2 and pH, and attenuated increases in LWCI and lung tissue MPO activity （all P〈0.01）. Moreover, SY Injection inhibited the increases in NF- K B p65 staining and in TNF-α, IL-1 β and IL-6 mRNA expression （all P〈0.01）, and promoted the expression of the antiinflammatory cytokine IL-10 （P〈0.05） following LPS injection. LPS-induced pulmonary p38 MAPK phosphorylation was suppressed by pretreatment with SY Injection （P〈0.01）. Conclusion： SY Injection ameliorates inflammatory ALl induced by LPS in mice.展开更多
目的:通过网络药理学和分子对接技术探讨红花黄色素注射液治疗心肌缺血的作用机制。方法:使用Targetnet、CTD、STITCH、ChEMBL等数据库获取红花黄色素注射液相关靶点;利用人类基因数据库和在线孟德尔人类遗传数据库搜集疾病靶点,找出红...目的:通过网络药理学和分子对接技术探讨红花黄色素注射液治疗心肌缺血的作用机制。方法:使用Targetnet、CTD、STITCH、ChEMBL等数据库获取红花黄色素注射液相关靶点;利用人类基因数据库和在线孟德尔人类遗传数据库搜集疾病靶点,找出红花黄色素注射液与疾病的共有交集靶点;利用STRING数据库和Cytoscape软件绘制靶点蛋白互作网络,利用DAVID数据库对靶点进行基因本体论功能富集分析(gene ontology,GO)和KEGG富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用Cytoscape软件构建成分-靶点-信号通路网络;在RyRx中调用AutoDock Vina算法进行模拟对接。结果:共获得红花黄色素注射液靶点90个,包括治疗心肌缺血靶点54个;白细胞介素6、肿瘤坏死因子、热休克蛋白90α家族A类成员1、淀粉样前体蛋白、基质金属蛋白酶9、半胱天冬氨酸蛋白酶8、雌激素受体1、过氧化物酶体增生激活受体γ、诱导型一氧化氮合酶2、细胞间黏附分子1为核心靶点。GO功能富集得到392个GO条目(P<0.05),KEGG通路富集得到17条信号通路(P<0.05),主要涉及肿瘤、病毒性心肌炎、凋亡、NOD样受体、Toll样受体(Toll like receptor,TLR)等信号通路。分子对接结果显示,主要活性成分与靶点亲和作用较好。结论:红花黄色素注射液治疗心肌缺血具有多基因多通路参与的特点,可能与调控炎性反应、氧化应激、细胞凋亡等有关。展开更多
基金Supported by National Natural Science Foundation of China(No.30572344)Natural Science Foundation of Beijing(No.7102025)Science and Technology Personnel ServeEnterprise Action(No.2009GJA30001)
文摘Objective： To observe the effect of Safflor Yellow （SY） Injection on acute lung injury （ALl） induced by lipopolysaccharide （LPS） in mice. Methods： Seventy-two mice were divided into six groups： control （saline ＋ saline）; LPS （LPS ＋ saline）; SY Injection [LPS ＋ SY （10, 20 or 40 mg/kg, intravenously）] and anisodamine （AD） （LPS ＋ AD）. Thirty minutes after SY or AD administration, 15 mg/kg LPS was given intraperitoneally. All animals were sacrificed 4 h after LPS injection. Arterial blood gas and lung water content index （LWCI） were measured. Lung tissue myeloperoxidase （MPO） activity was assayed, mRNA expression of inflammatory cytokines was assayed by reverse-transcription polymerase chain reaction. Lung morphological and nuclear factor （NF）- K B p65-positive cell changes were observed by HE and immunohistochemical staining, p38 mitogen-activated protein kinase （MAPK） phosphorylation was observed by Western blotting. Results： After LPS administration, all animals displayed increased arterial carbon dioxide partial pressure （PaCO2） and decreased arterial oxygen partial pressure （PaO2）, arterial oxygen saturation （SO2）, HCOs concentration and pH, and increased LWCI, MPO activity, interleukin （IL）-I β, IL-6 and tumor necrosis factor （TNF）-ot mRNA expression, NF-K B p65 positive staining and p38 MAPK activation compared with normal controls （all P〈0.01）. SY Injection significantly mitigated the LPS-induced increase in arterial PaCO2 and the decreases in arterial PaO2, SO2 and pH, and attenuated increases in LWCI and lung tissue MPO activity （all P〈0.01）. Moreover, SY Injection inhibited the increases in NF- K B p65 staining and in TNF-α, IL-1 β and IL-6 mRNA expression （all P〈0.01）, and promoted the expression of the antiinflammatory cytokine IL-10 （P〈0.05） following LPS injection. LPS-induced pulmonary p38 MAPK phosphorylation was suppressed by pretreatment with SY Injection （P〈0.01）. Conclusion： SY Injection ameliorates inflammatory ALl induced by LPS in mice.
文摘目的:通过网络药理学和分子对接技术探讨红花黄色素注射液治疗心肌缺血的作用机制。方法:使用Targetnet、CTD、STITCH、ChEMBL等数据库获取红花黄色素注射液相关靶点;利用人类基因数据库和在线孟德尔人类遗传数据库搜集疾病靶点,找出红花黄色素注射液与疾病的共有交集靶点;利用STRING数据库和Cytoscape软件绘制靶点蛋白互作网络,利用DAVID数据库对靶点进行基因本体论功能富集分析(gene ontology,GO)和KEGG富集分析(kyoto encyclopedia of genes and genomes,KEGG);利用Cytoscape软件构建成分-靶点-信号通路网络;在RyRx中调用AutoDock Vina算法进行模拟对接。结果:共获得红花黄色素注射液靶点90个,包括治疗心肌缺血靶点54个;白细胞介素6、肿瘤坏死因子、热休克蛋白90α家族A类成员1、淀粉样前体蛋白、基质金属蛋白酶9、半胱天冬氨酸蛋白酶8、雌激素受体1、过氧化物酶体增生激活受体γ、诱导型一氧化氮合酶2、细胞间黏附分子1为核心靶点。GO功能富集得到392个GO条目(P<0.05),KEGG通路富集得到17条信号通路(P<0.05),主要涉及肿瘤、病毒性心肌炎、凋亡、NOD样受体、Toll样受体(Toll like receptor,TLR)等信号通路。分子对接结果显示,主要活性成分与靶点亲和作用较好。结论:红花黄色素注射液治疗心肌缺血具有多基因多通路参与的特点,可能与调控炎性反应、氧化应激、细胞凋亡等有关。
