细胞因子信号转导异常可引起多种疾病,包括血液病、过敏性疾病及自身免疫性疾病等。细胞因子信号传导抑制蛋白（suppressor of cytokine signaling,SOCS）家族是一类由细胞因子诱导产生并反馈性阻断细胞因子信号转导过程的负性调节因子...细胞因子信号转导异常可引起多种疾病,包括血液病、过敏性疾病及自身免疫性疾病等。细胞因子信号传导抑制蛋白（suppressor of cytokine signaling,SOCS）家族是一类由细胞因子诱导产生并反馈性阻断细胞因子信号转导过程的负性调节因子。其中SOCS-1和SOCS-3是SOCS家族的重要分子,大量研究表明其可被多种炎症因子和抗炎因子诱导表达,并抑制多种免疫分子的信号传导。T细胞亚群在免疫应答和免疫调节方面发挥了关键作用。研究发现,SOCS-1、SOCS-3通过调节T细胞亚群的分化使其产生不同的免疫应答类型。展开更多
目的:探讨芡实对糖尿病肾病(diebetic nephrothy,DN)大鼠肾组织中细胞因子信号抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)及胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)表达的影响及可能机制。方法:采用单剂...目的:探讨芡实对糖尿病肾病(diebetic nephrothy,DN)大鼠肾组织中细胞因子信号抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)及胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)表达的影响及可能机制。方法:采用单剂量腹腔注射链脲佐菌素(STZ,45 mg/kg)建立大鼠DN模型,将DN模型大鼠随机分为5组:DN组(DN组)、小剂量芡实组(EL,1.5 g·kg-1·d-1)、中剂量芡实组(EM,3.0 g·kg·-1d-1)、大剂量芡实组(EH,6.0 g·kg-1·d-1)及氯沙坦钾组(LP,30 mg·kg-1·d-1);另设正常对照组(NC组),每组10只。分别治疗12周后测定各组大鼠生化指标;HE、Masson、PAS染色及电镜观察肾组织病理变化;免疫组化、Western blot法检测肾组织中SOCS-3与IGF-1表达情况。结果:12周末,与NC组相比,DN组大鼠24 h尿蛋白定量(24 h Upr)、尿素氮(BUN)及血肌酐(Scr)均明显升高(P<0.05),肾小球体积增大、系膜细胞增生、基质增多,肾小管扩张,肾组织中SOCS-3表达增加、IGF-1表达明显增加(P<0.05);与DN组相比,LP组与EM组大鼠24 h Upr、BUN及Scr明显降低(P<0.05),病理改变减轻,肾组织SOCS-3表达明显增加、IGF-1表达明显下降(P<0.05);LP组与EM组间降尿蛋白作用差异无统计学意义。结论:芡实可能通过上调SOCS-3表达,抑制IGF-1过表达进而减少蛋白尿,发挥肾脏保护作用。展开更多
Background: Interferon α(IFN-α) activated cellular sign- aling is negatively regulated by inhibitory factors, including the suppressor of cytokine signaling (SOCS) family. The effects of host factors such as obesity...Background: Interferon α(IFN-α) activated cellular sign- aling is negatively regulated by inhibitory factors, including the suppressor of cytokine signaling (SOCS) family. The effects of host factors such as obesity on hepatic expression of these inhibitory factors in subjects with chronic hepatitis C virus (HCV) are unknown. Objectives: To assess the independent effects of obesity, insulin resistance, and steatosis on response to IFN-αtherapy and to determine hepatic expression of factors inhibiting IFN-αsignaling in obese and non-obese subjects with chronic HCV. Methods: A total of 145 subjects were analysed to determine host factors associated with non-response to antiviral therapy. Treatment comprised IFN-αor peginterferon alpha, either alone or in combination with ribavirin. In a separate cohort of 73 patients, real time-polymerase chain reaction was performed to analyse hepatic mRNA expression. Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38 patients with viral genotype 1 who had received antiviral treatment. Results: Non-response (NR) to treatment occurred in 55%of patients with HCV genotypes 1 or 4 and 22%with genotypes 2 or 3. Factors independently associated with NR were viral genotype 1/4 (p < 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and body mass index ≥30 kg/m2 (p = 0.010). Obese subjects with viral genotype 1 had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p = 0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following multivariate analysis, SOCS-3 mRNA expression remained independently associated with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (p = 0.013) and in non-responders compared with responders (p = 0.014). Conclusions: In patients with chronic HCV viral genotype 1, increased expression of factors that inhibit interferon signaling may be one mechanism by which obesity reduces the biological response to IFN-α.展开更多
文摘细胞因子信号转导异常可引起多种疾病,包括血液病、过敏性疾病及自身免疫性疾病等。细胞因子信号传导抑制蛋白（suppressor of cytokine signaling,SOCS）家族是一类由细胞因子诱导产生并反馈性阻断细胞因子信号转导过程的负性调节因子。其中SOCS-1和SOCS-3是SOCS家族的重要分子,大量研究表明其可被多种炎症因子和抗炎因子诱导表达,并抑制多种免疫分子的信号传导。T细胞亚群在免疫应答和免疫调节方面发挥了关键作用。研究发现,SOCS-1、SOCS-3通过调节T细胞亚群的分化使其产生不同的免疫应答类型。
文摘目的:探讨芡实对糖尿病肾病(diebetic nephrothy,DN)大鼠肾组织中细胞因子信号抑制因子-3(suppressor of cytokine signaling-3,SOCS-3)及胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)表达的影响及可能机制。方法:采用单剂量腹腔注射链脲佐菌素(STZ,45 mg/kg)建立大鼠DN模型,将DN模型大鼠随机分为5组:DN组(DN组)、小剂量芡实组(EL,1.5 g·kg-1·d-1)、中剂量芡实组(EM,3.0 g·kg·-1d-1)、大剂量芡实组(EH,6.0 g·kg-1·d-1)及氯沙坦钾组(LP,30 mg·kg-1·d-1);另设正常对照组(NC组),每组10只。分别治疗12周后测定各组大鼠生化指标;HE、Masson、PAS染色及电镜观察肾组织病理变化;免疫组化、Western blot法检测肾组织中SOCS-3与IGF-1表达情况。结果:12周末,与NC组相比,DN组大鼠24 h尿蛋白定量(24 h Upr)、尿素氮(BUN)及血肌酐(Scr)均明显升高(P<0.05),肾小球体积增大、系膜细胞增生、基质增多,肾小管扩张,肾组织中SOCS-3表达增加、IGF-1表达明显增加(P<0.05);与DN组相比,LP组与EM组大鼠24 h Upr、BUN及Scr明显降低(P<0.05),病理改变减轻,肾组织SOCS-3表达明显增加、IGF-1表达明显下降(P<0.05);LP组与EM组间降尿蛋白作用差异无统计学意义。结论:芡实可能通过上调SOCS-3表达,抑制IGF-1过表达进而减少蛋白尿,发挥肾脏保护作用。
文摘Background: Interferon α(IFN-α) activated cellular sign- aling is negatively regulated by inhibitory factors, including the suppressor of cytokine signaling (SOCS) family. The effects of host factors such as obesity on hepatic expression of these inhibitory factors in subjects with chronic hepatitis C virus (HCV) are unknown. Objectives: To assess the independent effects of obesity, insulin resistance, and steatosis on response to IFN-αtherapy and to determine hepatic expression of factors inhibiting IFN-αsignaling in obese and non-obese subjects with chronic HCV. Methods: A total of 145 subjects were analysed to determine host factors associated with non-response to antiviral therapy. Treatment comprised IFN-αor peginterferon alpha, either alone or in combination with ribavirin. In a separate cohort of 73 patients, real time-polymerase chain reaction was performed to analyse hepatic mRNA expression. Immunohistochemistry for SOCS-3 was performed on liver biopsy samples from 38 patients with viral genotype 1 who had received antiviral treatment. Results: Non-response (NR) to treatment occurred in 55%of patients with HCV genotypes 1 or 4 and 22%with genotypes 2 or 3. Factors independently associated with NR were viral genotype 1/4 (p < 0.001), cirrhosis on pretreatment biopsy (p = 0.025), and body mass index ≥30 kg/m2 (p = 0.010). Obese subjects with viral genotype 1 had increased hepatic mRNA expression of phosphoenolpyruvate carboxy kinase (p = 0.01) and SOCS-3 (p = 0.047), in comparison with lean subjects. Following multivariate analysis, SOCS-3 mRNA expression remained independently associated with obesity (p = 0.023). SOCS-3 immunoreactivity was significantly increased in obesity (p = 0.013) and in non-responders compared with responders (p = 0.014). Conclusions: In patients with chronic HCV viral genotype 1, increased expression of factors that inhibit interferon signaling may be one mechanism by which obesity reduces the biological response to IFN-α.
