Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues ...Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.展开更多
目的:观察游泳运动对高脂诱导的胰岛素抵抗(IR)大鼠骨骼肌脂质沉积相关基因及MG53的影响,探讨MG53-IRS1通路在胰岛素抵抗发生中的作用,为运动防治胰岛素抵抗提供理论依据。方法:以SD大鼠为实验对象,随机分为3组:普通饮食对照组(C组)、...目的:观察游泳运动对高脂诱导的胰岛素抵抗(IR)大鼠骨骼肌脂质沉积相关基因及MG53的影响,探讨MG53-IRS1通路在胰岛素抵抗发生中的作用,为运动防治胰岛素抵抗提供理论依据。方法:以SD大鼠为实验对象,随机分为3组:普通饮食对照组(C组)、高脂饮食IR模型组(H组)、高脂饮食90min运动组(HE组)。通过8周高脂饲料喂养建立IR大鼠动物模型,同时对HE组大鼠实施每天2次45min无负重游泳运动干预。运用正糖钳技术结合HOMA-IR、ISI综合评价动物模型的建立;通过观察运动对高脂饮食大鼠骨骼肌甘油三酯(TG)含量,骨骼肌PPARγ的辅激活子-1(PGC-1α)、脂肪酸转位酶FAT/CD36、MG53和胰岛素受体底物-1(IRS-1)m RNA的表达量及p IRS-1Ser307、IRS-1蛋白表达水平的变化,探讨运动干预IR的机制。结果:(1)IR动物模型评价:8周高脂饮食喂养后,与C组相比,H组大鼠葡萄糖输注速率(GIR)显著下降(P<0.01),ISI水平显著下降(P<0.01),HOMA-IR水平显著增加(P<0.01),提示胰岛素抵抗大鼠建模成功。(2)运动对IR的影响:8周游泳干预后,与H组相比,HE组大鼠GIR显著增加(P<0.01),血清胰岛素含量和HOMA-IR水平均显著降低(P<0.01),ISI水平显著增加(P<0.01);HE组大鼠骨骼肌TG含量显著下降(P<0.05),PGC-1-α和FAT/CD36 m RNA表达量均显著降低(P<0.01),骨骼肌MG53 m RNA和蛋白表达水平均显著下降(P<0.05,P<0.01),骨骼肌IRS-1 m RNA表达量水平显著增加(P<0.01),p IRS-1Ser307表达水平显著下降(P<0.01),IRS-1蛋白表达水平显著增加(P<0.05)。结论:8周游泳运动可以通过减少骨骼肌脂质沉积,降低大鼠骨骼肌MG53表达水平,增加IRS-1的表达,从而可能通过增强胰岛素信号转导,延缓高脂饮食大鼠IR的发生。展开更多
目的:研究有氧运动对自发性高血压大鼠心脏形态与功能的影响,并探讨MG53/NF-κB信号通路在有氧运动调控高血压心脏重塑中的可能作用,为高心病的防治提供实验依据。方法:正常血压对照大鼠(Wistar-Kyoto rat,WKY)随机分为正常血压运动组(W...目的:研究有氧运动对自发性高血压大鼠心脏形态与功能的影响,并探讨MG53/NF-κB信号通路在有氧运动调控高血压心脏重塑中的可能作用,为高心病的防治提供实验依据。方法:正常血压对照大鼠(Wistar-Kyoto rat,WKY)随机分为正常血压运动组(WKY-EX)和正常血压安静组(WKYSED);自发性高血压大鼠(spontaneously hypertensive rat,SHR)随机分为高血压运动组(SHR-EX)和高血压安静组(SHR-SED);每组12只;3月龄雄性。经12周跑台训练(坡度0°,20m/min,5d/w),测量尾动脉血压;Millar压力-容积系统测定心功能;WGA染色分析心肌细胞横截面积;Masson染色分析心肌胶原容积分数(CVF%);实时荧光定量PCR测定心钠肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、MG53和NF-κB p65 m RNA相对表达量;蛋白免疫印迹测定心肌MG53、NF-κB p65和p-NF-κB p65蛋白表达。结果:(1)12周有氧运动可有效降低SHR的心率和收缩压;(2)SHR-SED组CVF%和心肌细胞横截面积显著高于WKY-SED组(P<0.01),SHR-EX组CVF%显著低于SHR-SED组(P<0.01),心肌细胞横截面积无显著性差异(P>0.05);(3)与WKY-SED组相比,SHR-SED组射血分数(EF)、左心室内压上升最大速率(+dp/dtmax)和左心室内压下降最大速率(-dp/dtmax)绝对值均显著下降(P<0.01),与SHR-SED组相比,SHR-EX组EF(P<0.05)、+dp/dtmax(P<0.05)和-dp/dtmax绝对值(P<0.01)均显著增高;(4)与WKY-SED组相比,SHR-SED组心肌ANP和BNP m RNA表达量显著增加(P<0.01),NF-κB p65 m RNA表达量也显著增加(P<0.05),MG53 m RNA表达量无显著性差异(P>0.05);与SHRSED组相比,SHR-EX组心肌ANP、BNP和NF-κB p65 m RNA表达量显著降低(P<0.01),MG53 m RNA表达量显著增加(P<0.01);(5)与WKY-SED组相比,SHR-SED组心肌MG53蛋白表达水平无显著性差异(P>0.05),NF-κB p65蛋白相对磷酸化水平显著升高(P<0.01),与SHR-SED组相比,SHR-EX组心肌MG53蛋白表达水平显著升高(P<0.01),NF-κB p65蛋白相对磷酸化水平显著下降(P<0.01)。结论:有氧运动可能通过上调MG53抑制NF-κB表达,从而改善高血压心脏功能,延缓高血压性心脏病的发生发展。展开更多
基金China's NSFC grants (81027004,81372082, 30571922) to JW and GL, "863" grants (2012AA020504)to JW. Also we sincerely thank Jianjie Ma for selfless assistance to this work
文摘Mitsugumin 53 (MG53), a newly identified muscle-specific protein, is an essential component of the cell membrane repair machinery in skeletal and cardiac muscle. However, the role of MG53 after burns in other tissues remains unclear. This study aims to investigate the possible roles of MG53 in the protection of the kidney after severe burn injury, and an animal scalding model of 30% of total body surface area (TBSA) was used. Recombinant human MG53 (rhMG53) or bovine serum albumin (BSA) was injected intravenously via the tail vein. Data showed that the mortality in the MG53-treated group was lower than that in control group. Administration of rhMG53 may alleviate histological alterations in renal tubular epithelial cells after burn injury. Renal tubular injury scores and the average optical density score of kidney injury molecule-1 (KIM-1) immunohistochemical staining in the MG53-treated group were significantly lower than those in control group (P < 0.001). Exogenous rhMG53 was found to be located in renal tubular epithelial cells. Numerous polymerase I and transcript release factor (PTRF) were expressed in the mouse kidney after severe scalding. In conclusion, our data indicate that MG53 protein protects the kidney by involving local PTRF after severe burn injury.
文摘目的:观察游泳运动对高脂诱导的胰岛素抵抗(IR)大鼠骨骼肌脂质沉积相关基因及MG53的影响,探讨MG53-IRS1通路在胰岛素抵抗发生中的作用,为运动防治胰岛素抵抗提供理论依据。方法:以SD大鼠为实验对象,随机分为3组:普通饮食对照组(C组)、高脂饮食IR模型组(H组)、高脂饮食90min运动组(HE组)。通过8周高脂饲料喂养建立IR大鼠动物模型,同时对HE组大鼠实施每天2次45min无负重游泳运动干预。运用正糖钳技术结合HOMA-IR、ISI综合评价动物模型的建立;通过观察运动对高脂饮食大鼠骨骼肌甘油三酯(TG)含量,骨骼肌PPARγ的辅激活子-1(PGC-1α)、脂肪酸转位酶FAT/CD36、MG53和胰岛素受体底物-1(IRS-1)m RNA的表达量及p IRS-1Ser307、IRS-1蛋白表达水平的变化,探讨运动干预IR的机制。结果:(1)IR动物模型评价:8周高脂饮食喂养后,与C组相比,H组大鼠葡萄糖输注速率(GIR)显著下降(P<0.01),ISI水平显著下降(P<0.01),HOMA-IR水平显著增加(P<0.01),提示胰岛素抵抗大鼠建模成功。(2)运动对IR的影响:8周游泳干预后,与H组相比,HE组大鼠GIR显著增加(P<0.01),血清胰岛素含量和HOMA-IR水平均显著降低(P<0.01),ISI水平显著增加(P<0.01);HE组大鼠骨骼肌TG含量显著下降(P<0.05),PGC-1-α和FAT/CD36 m RNA表达量均显著降低(P<0.01),骨骼肌MG53 m RNA和蛋白表达水平均显著下降(P<0.05,P<0.01),骨骼肌IRS-1 m RNA表达量水平显著增加(P<0.01),p IRS-1Ser307表达水平显著下降(P<0.01),IRS-1蛋白表达水平显著增加(P<0.05)。结论:8周游泳运动可以通过减少骨骼肌脂质沉积,降低大鼠骨骼肌MG53表达水平,增加IRS-1的表达,从而可能通过增强胰岛素信号转导,延缓高脂饮食大鼠IR的发生。
文摘目的:研究有氧运动对自发性高血压大鼠心脏形态与功能的影响,并探讨MG53/NF-κB信号通路在有氧运动调控高血压心脏重塑中的可能作用,为高心病的防治提供实验依据。方法:正常血压对照大鼠(Wistar-Kyoto rat,WKY)随机分为正常血压运动组(WKY-EX)和正常血压安静组(WKYSED);自发性高血压大鼠(spontaneously hypertensive rat,SHR)随机分为高血压运动组(SHR-EX)和高血压安静组(SHR-SED);每组12只;3月龄雄性。经12周跑台训练(坡度0°,20m/min,5d/w),测量尾动脉血压;Millar压力-容积系统测定心功能;WGA染色分析心肌细胞横截面积;Masson染色分析心肌胶原容积分数(CVF%);实时荧光定量PCR测定心钠肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、MG53和NF-κB p65 m RNA相对表达量;蛋白免疫印迹测定心肌MG53、NF-κB p65和p-NF-κB p65蛋白表达。结果:(1)12周有氧运动可有效降低SHR的心率和收缩压;(2)SHR-SED组CVF%和心肌细胞横截面积显著高于WKY-SED组(P<0.01),SHR-EX组CVF%显著低于SHR-SED组(P<0.01),心肌细胞横截面积无显著性差异(P>0.05);(3)与WKY-SED组相比,SHR-SED组射血分数(EF)、左心室内压上升最大速率(+dp/dtmax)和左心室内压下降最大速率(-dp/dtmax)绝对值均显著下降(P<0.01),与SHR-SED组相比,SHR-EX组EF(P<0.05)、+dp/dtmax(P<0.05)和-dp/dtmax绝对值(P<0.01)均显著增高;(4)与WKY-SED组相比,SHR-SED组心肌ANP和BNP m RNA表达量显著增加(P<0.01),NF-κB p65 m RNA表达量也显著增加(P<0.05),MG53 m RNA表达量无显著性差异(P>0.05);与SHRSED组相比,SHR-EX组心肌ANP、BNP和NF-κB p65 m RNA表达量显著降低(P<0.01),MG53 m RNA表达量显著增加(P<0.01);(5)与WKY-SED组相比,SHR-SED组心肌MG53蛋白表达水平无显著性差异(P>0.05),NF-κB p65蛋白相对磷酸化水平显著升高(P<0.01),与SHR-SED组相比,SHR-EX组心肌MG53蛋白表达水平显著升高(P<0.01),NF-κB p65蛋白相对磷酸化水平显著下降(P<0.01)。结论:有氧运动可能通过上调MG53抑制NF-κB表达,从而改善高血压心脏功能,延缓高血压性心脏病的发生发展。
