目的探讨血清补体C1q/肿瘤坏死因子相关蛋白13(CTRP13)与妊娠期糖尿病(GDM)的相关性.方法选取GDM患者为GDM组(n=55),正常妊娠者为NGT组(n=50).对比两组基线资料及血清CTRP13水平.Logistic回归分析GDM影响因素,Pearson相关性分析血清CTR...目的探讨血清补体C1q/肿瘤坏死因子相关蛋白13(CTRP13)与妊娠期糖尿病(GDM)的相关性.方法选取GDM患者为GDM组(n=55),正常妊娠者为NGT组(n=50).对比两组基线资料及血清CTRP13水平.Logistic回归分析GDM影响因素,Pearson相关性分析血清CTRP13与临床指标的相关性,多元线性回归分析血清CTRP13的影响因素.结果相较于NGT组,GDM组FPG、1hPG、2hPG、FIns、HOMA-IR、HbA1c、IL-6、TNF-α增高,血清CTRP13水平降低(56.90±10.73 ng/mL vs 75.98±15.20 ng/mL)(P<0.05).两组年龄、孕周、BMI、SBP、DBP、TG、TC、LDL-C、HDL-C比较差异无统计学意义(P>0.05).血清CTRP13与FPG、1hPG、2hPG、HOMA-IR、IL-6及TNF-α呈负相关(P<0.05).FPG、IL-6是CTRP13的影响因素.HOMA-IR及CTRP13是GDM的影响因素.结论GDM患者血清CTRP13低表达,是GDM的独立危险因素,CTRP13可能参与GDM病程进展.展开更多
Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle ce...Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.展开更多
目的探讨胰高血糖素样肽-1(GLP-1)激动剂利拉鲁肽对2型糖尿病(T2DM)合并动脉粥样硬化患者血管重构、肠道菌群代谢物及血清C1q/肿瘤坏死因子相关蛋白13(CTRP13)的影响。方法选择2021年6月至2024年6月于该院接受治疗的214例T2DM合并动脉...目的探讨胰高血糖素样肽-1(GLP-1)激动剂利拉鲁肽对2型糖尿病(T2DM)合并动脉粥样硬化患者血管重构、肠道菌群代谢物及血清C1q/肿瘤坏死因子相关蛋白13(CTRP13)的影响。方法选择2021年6月至2024年6月于该院接受治疗的214例T2DM合并动脉粥样硬化患者,采用随机数字表法分为观察组与对照组,每组107例。对照组在常规治疗基础上给予二甲双胍治疗,观察组在对照组基础上给予利拉鲁肽治疗。比较2组患者治疗前后血糖[餐后2小时血糖(2 h PG)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)]、血脂[高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)]、血压[舒张压(DBP)、收缩压(SBP)]、血管重构指标、肠道菌群代谢物[三甲胺氧化物(TMAO)]、炎症因子[C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]及CTRP13水平,以及临床疗效和不良反应情况。结果观察组总有效率为87.9%,高于对照组的65.4%(P<0.05)。治疗后2组血糖、血压、LDL-C、TG、TC水平明显下降,且观察组低于对照组,治疗后2组HDL-C水平明显升高,且观察组HDL-C水平高于对照组,差异均有统计学意义(P<0.05)。与治疗前相比,2组患者CTRP13水平均升高,而TMAO水平均降低,且观察组CTRP13水平高于对照组,TMAO水平低于对照组,差异均有统计学意义(P<0.05)。与治疗前相比,2组患者治疗后CRP、IL-6、TNF-α水平降低(P<0.05),且观察组低于对照组(P<0.05)。治疗后观察组颈内动脉内膜中层厚度(IMT)、不稳定斑块检出率低于对照组(P<0.05)。观察组治疗前后血管正性重构发生率及负性重塑发生率比较,差异均无统计学意义(P>0.05)。对照组、观察组不良反应发生率分别为14.0%、16.8%,差异无统计学意义(χ^(2)=0.322,P=0.570)。结论利拉鲁肽有利于控制T2DM合并动脉粥样硬化患者血糖、血脂、血压水平,减少TMAO释放,提升CTRP13水平,减轻机体炎症反应,改善血管重构,降低IMT,稳定斑块,且安全性较好。展开更多
文摘目的探讨血清补体C1q/肿瘤坏死因子相关蛋白13(CTRP13)与妊娠期糖尿病(GDM)的相关性.方法选取GDM患者为GDM组(n=55),正常妊娠者为NGT组(n=50).对比两组基线资料及血清CTRP13水平.Logistic回归分析GDM影响因素,Pearson相关性分析血清CTRP13与临床指标的相关性,多元线性回归分析血清CTRP13的影响因素.结果相较于NGT组,GDM组FPG、1hPG、2hPG、FIns、HOMA-IR、HbA1c、IL-6、TNF-α增高,血清CTRP13水平降低(56.90±10.73 ng/mL vs 75.98±15.20 ng/mL)(P<0.05).两组年龄、孕周、BMI、SBP、DBP、TG、TC、LDL-C、HDL-C比较差异无统计学意义(P>0.05).血清CTRP13与FPG、1hPG、2hPG、HOMA-IR、IL-6及TNF-α呈负相关(P<0.05).FPG、IL-6是CTRP13的影响因素.HOMA-IR及CTRP13是GDM的影响因素.结论GDM患者血清CTRP13低表达,是GDM的独立危险因素,CTRP13可能参与GDM病程进展.
文摘Background The present study aimed to investigate the detailed mode and specific sites for their binding as well as the functional relevance of this binding in the phenotypic proliferation of vascular smooth muscle cells(SMCs). Methods CREG knocked-down SMCs were employed to evaluate the biological activity of wtCREG and mCREG.Expressions of SMC differentiation markers SM myosin heavy chain(SM-MHC),SM-actin,heavy caldesmon and myocardin were determined by Western blotting using specific antibodies. Cellular growth of SMCs was assessed by bromide dewuridine (BrdU) incorporation and cell cycle analysis on fluorescence-activated cell sorting(FACS).A solid-phase binding assay was used to study the binding of CREG to extracellular domains of M6P/IGF2R.The cellular co-localization of the two recombinant CREGs with M6P/IGF2R was detected on SMC surface by immunoprecipitation and immunofluorescence analysis.Results The molecular weight of wtCREG was around 30 kD while that of the mCREG was～25 kD.Treatment of wtCREG with PNGase F reduced its molecular weight from～30 kD to～25 kD,whereas PNGase F treatment had no effect on the molecular weight of mCREG.Both wtCREG and mCREG proteins enhanced SMC differentiation,inhibited BrdU incorporation,and arrested cell cycle progression when added to the culture medium.In CREG knocked-down SMCs,the amount of CREG detected by immunoblotting in M6P/IGF2R immunoprecipitates was significantly reduced when compared to normal cells.Both recombinant CREGs co-immunoprecipitated with M6P/IGF2R, although slightly reduced amount of the mutant CREG was detected in M6P/IGF2R immunoprecipitates.Immunostaining revealed that His-tagged CREGs co-localized with IGF2R on the cell surface in a glycosylation-independent manner.In vitro binding assay showed that CREGs bound to M6P/ IGF2R extracellular domains 7-10 and 11-13 in a glycosylation -dependent and -independent manner,respectively.Further blocking experiments using soluble M6P/IGF2R fragments and M6P/IGF2R neutralizing antibody indicated that the biological activities of recombinant CREGs in SMC growth and the up-regulation of SMC differentiation markers were all abolished by treatment with the M6P/IGF2R neutralizing antibody. However,although the growth inhibitory effect of wtCREG was nearly abolished by D7-10 or D11-13,the effect of mCREG was only reversed by Dll-13,indicating that the binding to domains 11-13 is required for CREG to modulate the proliferation of SMCs.Conclusions These data suggest that solubleCREG proteins can exert their biological function via binding to the extracellular domains 7-10 and 11-13 of cell surface M6P/IGF2R in both a glycosylation-dependent and -independent manner.
文摘目的探讨胰高血糖素样肽-1(GLP-1)激动剂利拉鲁肽对2型糖尿病(T2DM)合并动脉粥样硬化患者血管重构、肠道菌群代谢物及血清C1q/肿瘤坏死因子相关蛋白13(CTRP13)的影响。方法选择2021年6月至2024年6月于该院接受治疗的214例T2DM合并动脉粥样硬化患者,采用随机数字表法分为观察组与对照组,每组107例。对照组在常规治疗基础上给予二甲双胍治疗,观察组在对照组基础上给予利拉鲁肽治疗。比较2组患者治疗前后血糖[餐后2小时血糖(2 h PG)、空腹血糖(FPG)、糖化血红蛋白(HbA1c)]、血脂[高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、总胆固醇(TC)]、血压[舒张压(DBP)、收缩压(SBP)]、血管重构指标、肠道菌群代谢物[三甲胺氧化物(TMAO)]、炎症因子[C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]及CTRP13水平,以及临床疗效和不良反应情况。结果观察组总有效率为87.9%,高于对照组的65.4%(P<0.05)。治疗后2组血糖、血压、LDL-C、TG、TC水平明显下降,且观察组低于对照组,治疗后2组HDL-C水平明显升高,且观察组HDL-C水平高于对照组,差异均有统计学意义(P<0.05)。与治疗前相比,2组患者CTRP13水平均升高,而TMAO水平均降低,且观察组CTRP13水平高于对照组,TMAO水平低于对照组,差异均有统计学意义(P<0.05)。与治疗前相比,2组患者治疗后CRP、IL-6、TNF-α水平降低(P<0.05),且观察组低于对照组(P<0.05)。治疗后观察组颈内动脉内膜中层厚度(IMT)、不稳定斑块检出率低于对照组(P<0.05)。观察组治疗前后血管正性重构发生率及负性重塑发生率比较,差异均无统计学意义(P>0.05)。对照组、观察组不良反应发生率分别为14.0%、16.8%,差异无统计学意义(χ^(2)=0.322,P=0.570)。结论利拉鲁肽有利于控制T2DM合并动脉粥样硬化患者血糖、血脂、血压水平,减少TMAO释放,提升CTRP13水平,减轻机体炎症反应,改善血管重构,降低IMT,稳定斑块,且安全性较好。
