Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in rece...Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.展开更多
目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生...目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生理盐水与治疗剂量的连梅汤(LMD) 21天。第22天,PBS注入对照组腹腔,另两组LPS注入5 mg/kg腹腔,建立脓毒症模型小鼠。腹腔注射24小时后进行回肠和肝、肺组织的收集。用HE染色组织病理鉴定;通过RT-qPCR检测回肠屏障因子水平(ZO-1, Occludin)和肝肺组织炎性因子(IL-1α, IL-8, TNF-α)。结果LPS组与CON相比,体重下降明显(n = 6;P β、IL-8、TNF-α)水平(n = 6;P Objective: The protective effect of Lianmei Decoction on the intestine was studied to the intestinal barrier, liver, and lung damage caused by lipopolysaccharide (LPS) in septic mice. Methods: C57/6J male mice were randomly assigned to the control group (CON group), LPS model group (LPS group), and Lianmei Decoction treatment group (LMD group), with 6 mice in each group. After 7 days of adaptive feeding, normal saline and a therapeutic dose of LMD were given orally for 21 days. In the 22 days of the study, PBS was injected intraperitoneally into the CON group, and 5 mg/kg LPS was administered intraperitoneally to the remaining two groups to create a sepsis mouse model. Ileum, liver, and lung tissues were gathered 24 hours after intraperitoneal injection. Histopathological examination was done using HE staining;the amounts of ileal barrier factors (ZO-1, Occludin) and inflammatory factors (IL-1β, IL-8, TNF-α) in liver and lung tissues were detected by RT-qPCR. Results: Compared with the CON group, the body weight of the LPS group decreased dramatically (n = 6;P β, IL-8, TNF-a) in liver and lung tissues (n = 6;P < 0.05), reduce the pathological damage of liver and pulmonary tissue. Conclusion: Lianmei Decoction can effectively improve ileal barrier damage, liver and lung injury, and inflammatory imbalance in LPS-induced sepsis mice.展开更多
目的:探讨胎盘间充质干细胞(PMSCs)对脂多糖(LPS)处理后星形胶质细胞的作用机制。方法:从新生大鼠脑皮质分离、培养星形胶质细胞,采用免疫荧光染色鉴定纯化培养的星形胶质细胞神经胶质纤维酸性蛋白(GFAP)表达。将PMSCs与经LPS处理的P3...目的:探讨胎盘间充质干细胞(PMSCs)对脂多糖(LPS)处理后星形胶质细胞的作用机制。方法:从新生大鼠脑皮质分离、培养星形胶质细胞,采用免疫荧光染色鉴定纯化培养的星形胶质细胞神经胶质纤维酸性蛋白(GFAP)表达。将PMSCs与经LPS处理的P3代星形胶质细胞共培养后,通过real time RT-PCR或Western blot技术检测各组星形胶质细胞炎症相关因子白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、精氨酸酶-1(Arg-1)、S100钙结合蛋白A10(S100A10)以及TGF-β/Smad信号通路相关蛋白的表达水平。结果:80%的P3代星形胶质细胞GFAP表达阳性。星形胶质细胞经10μg/ml LPS处理后,其GFAP、IL-1β、iNOS、TNF-α及IL-6的表达水平明显升高(P<0.05),抗炎因子Arg-1、S100A10表达水平下降(P<0.05);同时其TGF-β/Smad信号通路相关蛋白转化生长因子-β1(TGF-β1)、转化生长因子-βI型受体(TβRI)、转化生长因子-βⅡ型受体(TβRⅡ)、磷酸化Smad2和磷酸化Smad3(p-Smad2,p-Smad3)表达水平上调(P<0.05)。将PMSCs与经LPS处理的星形胶质细胞共培养后,星形胶质细胞GFAP、IL-1β、iNOS、TNF-α及IL-6表达水平明显下降(P<0.05),抗炎因子Arg-1、S100A10表达水平升高(P<0.05);同时其TGF-β/Smad信号通路相关蛋白TGF-β1、TβRI、TβRⅡ、p-Smad2和p-Smad3表达水平下调(P<0.05)。结论:胎盘间充质干细胞能够通过TGF-β/Smad信号通路抑制A1型星形胶质细胞的活化。展开更多
文摘Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.
文摘目的:由连梅汤(LMD)对脂多糖(LPS)诱导的脓毒症小鼠回肠屏障及肝肺损伤的保护作用的研究。方法:采用随机方式,将C57/6J雄性小鼠分为对照组(CON组)、LPS模型组(LPS组)和连梅汤治疗组(LMD组),每组各6只。适应性喂养7天后,分别经口给予生理盐水与治疗剂量的连梅汤(LMD) 21天。第22天,PBS注入对照组腹腔,另两组LPS注入5 mg/kg腹腔,建立脓毒症模型小鼠。腹腔注射24小时后进行回肠和肝、肺组织的收集。用HE染色组织病理鉴定;通过RT-qPCR检测回肠屏障因子水平(ZO-1, Occludin)和肝肺组织炎性因子(IL-1α, IL-8, TNF-α)。结果LPS组与CON相比,体重下降明显(n = 6;P β、IL-8、TNF-α)水平(n = 6;P Objective: The protective effect of Lianmei Decoction on the intestine was studied to the intestinal barrier, liver, and lung damage caused by lipopolysaccharide (LPS) in septic mice. Methods: C57/6J male mice were randomly assigned to the control group (CON group), LPS model group (LPS group), and Lianmei Decoction treatment group (LMD group), with 6 mice in each group. After 7 days of adaptive feeding, normal saline and a therapeutic dose of LMD were given orally for 21 days. In the 22 days of the study, PBS was injected intraperitoneally into the CON group, and 5 mg/kg LPS was administered intraperitoneally to the remaining two groups to create a sepsis mouse model. Ileum, liver, and lung tissues were gathered 24 hours after intraperitoneal injection. Histopathological examination was done using HE staining;the amounts of ileal barrier factors (ZO-1, Occludin) and inflammatory factors (IL-1β, IL-8, TNF-α) in liver and lung tissues were detected by RT-qPCR. Results: Compared with the CON group, the body weight of the LPS group decreased dramatically (n = 6;P β, IL-8, TNF-a) in liver and lung tissues (n = 6;P < 0.05), reduce the pathological damage of liver and pulmonary tissue. Conclusion: Lianmei Decoction can effectively improve ileal barrier damage, liver and lung injury, and inflammatory imbalance in LPS-induced sepsis mice.
文摘目的:探讨胎盘间充质干细胞(PMSCs)对脂多糖(LPS)处理后星形胶质细胞的作用机制。方法:从新生大鼠脑皮质分离、培养星形胶质细胞,采用免疫荧光染色鉴定纯化培养的星形胶质细胞神经胶质纤维酸性蛋白(GFAP)表达。将PMSCs与经LPS处理的P3代星形胶质细胞共培养后,通过real time RT-PCR或Western blot技术检测各组星形胶质细胞炎症相关因子白细胞介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、精氨酸酶-1(Arg-1)、S100钙结合蛋白A10(S100A10)以及TGF-β/Smad信号通路相关蛋白的表达水平。结果:80%的P3代星形胶质细胞GFAP表达阳性。星形胶质细胞经10μg/ml LPS处理后,其GFAP、IL-1β、iNOS、TNF-α及IL-6的表达水平明显升高(P<0.05),抗炎因子Arg-1、S100A10表达水平下降(P<0.05);同时其TGF-β/Smad信号通路相关蛋白转化生长因子-β1(TGF-β1)、转化生长因子-βI型受体(TβRI)、转化生长因子-βⅡ型受体(TβRⅡ)、磷酸化Smad2和磷酸化Smad3(p-Smad2,p-Smad3)表达水平上调(P<0.05)。将PMSCs与经LPS处理的星形胶质细胞共培养后,星形胶质细胞GFAP、IL-1β、iNOS、TNF-α及IL-6表达水平明显下降(P<0.05),抗炎因子Arg-1、S100A10表达水平升高(P<0.05);同时其TGF-β/Smad信号通路相关蛋白TGF-β1、TβRI、TβRⅡ、p-Smad2和p-Smad3表达水平下调(P<0.05)。结论:胎盘间充质干细胞能够通过TGF-β/Smad信号通路抑制A1型星形胶质细胞的活化。
