目的探讨沉默交配型信息调节2同系物-1(silent mating type information regulation2 homolog 1,SIRT1)激活剂SRT1720对重度失血性休克/复苏致大鼠急性肾损伤的治疗作用及机制。方法模型组、SIRT1激活剂SRT1720低、中、高剂量组(20、40...目的探讨沉默交配型信息调节2同系物-1(silent mating type information regulation2 homolog 1,SIRT1)激活剂SRT1720对重度失血性休克/复苏致大鼠急性肾损伤的治疗作用及机制。方法模型组、SIRT1激活剂SRT1720低、中、高剂量组(20、40、80mg/kg)建立重度失血性休克/复苏致大鼠急性肾损伤模型,建模成功后SIRT1激活剂SRT1720各剂量组给予相应药物,对照组、模型组给予等体积生理盐水;随后处死大鼠,测定肾/体比值、肌酐(SCr)、尿素氮(BUN)、肾脏SIRT1、信号转导转录激活剂-3(signal transducers and activators of transcription factor 3,STAT3)mRNA和蛋白水平、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。结果与对照组比较,模型组肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α升高(t值分别为25.632、14.524、18.965、23.654、23.654、18.695、19.547,P均<0.001);与模型组比较,SRT1720各剂量组肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α降低(t=21.526、19.654、23.654、25.148,32.654、19.654、21.548、25.965、24.967、28.741、30.365、31.654、23.654、18.475、26.548、29.512,30.248、24.659、24.965、22.698、26.985,P均<0.001),且随着SRT1720给药剂量的增加,肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α逐渐降低,剂量-效应关系明显(t=38.632、19.625、25.847、27.489、26.954、29.547、32.685、34.489、32.362、24.548、29.654、28.415、35.957、32.548,P均<0.001)。与对照组比较,模型组肾SIRT1 mRNA和蛋白水平降低(t=38.635、32.145,P均<0.001),STAT3 m RNA水平升高(t=32.636、30.213,P均<0.001);与模型组比较,SRT1720各剂量组SIRT1 mRNA和蛋白水平升高(t=18.965、23.147、28.476、30.216、23.654、28.471,P均<0.001),STAT3 mRNA和蛋白水平降低(t=22.654、25.489、29.548、33.265、41.326、29.635,P均<0.001),且随着SRT1720给药剂量增加,SIRT1 m RNA和蛋白水平逐渐升高,STAT3 mRNA和蛋白水平逐渐降低,剂量-效应关系明显(t=27.485、28.459、30.215、29.584、29.654、31.145、32.159、30.269,P均<0.001)。结论SIRT1激活剂SRT1720能减轻重度失血性休克/复苏致大鼠急性肾损伤;其机制与SIRT1激活剂SRT1720通过激活大鼠肾脏中SIRT1表达,抑制STAT3表达进而抑制炎性介质表达有关。展开更多
Objective To study the effects of hypotensive resuscitation and larger volume fluid resuscitation on uncontrolled hemorrhagic shock and survival in rats with a standardized massive splenic injury model（MSI）.Methods ...Objective To study the effects of hypotensive resuscitation and larger volume fluid resuscitation on uncontrolled hemorrhagic shock and survival in rats with a standardized massive splenic injury model（MSI）.Methods Following the MSI model,fifty Wistar rats were randomly and equally divided into five groups,group 1:sham-operated group,group 2: shock untreated group,group 3:normal MAP resuscitation group（during acute resuscitation phase MAP was kept at 80 mm Hg）,group 4:Hypotensive resuscitation group（during acute resuscitation phase MAP was kept at（60±5） mm Hg）,and group 5:larger volume fluid resuscitation with hypotensive resuscitation group(during acute resuscitation phase MAP was kept at（60±5） mm Hg,simultaneously infused SNP at 5 μg·kg-1·min-1).Results The mean survival time in group 1～5 was 180 min,73.50 min±8.04 min,114.30 min±31.33 min,146.70 min±28.07 min and 171.60 min±15.74 min respectively.Statistic significances were seen in each group（P<0.05）,except between group 1 and group 5（P=0.0671）.The amount of bleeding in group 2～5（during acute resuscitation phase） was 3.79 ml/kg±1.39 ml/kg、17.41 ml/kg±8.88 ml/kg、8.67 ml/kg±4.59 ml/kg and 10.33 ml/kg±4.31 ml/kg respectively.The loss of blood in group 3 was significantly more than other groups（P<0.05）.Group 4 and 5 enhanced the blood loss significantly compared with group 2（P<0.05）.The histopathologic of liver and renal showed that histopathologic injury is severe in group 3 compared with group 4,and histopathologic injury is not in evidence in group 5.Conclusion Hypotensive resuscitation and adding SNP at proper dose additionally could improve tissue metabolism and prolong survival time during hypotensive resuscitation from uncontrolled hemorrhagic shock.It is a more ideal resuscitation method compared with normal blood pressure resuscitation.展开更多
文摘目的探讨沉默交配型信息调节2同系物-1(silent mating type information regulation2 homolog 1,SIRT1)激活剂SRT1720对重度失血性休克/复苏致大鼠急性肾损伤的治疗作用及机制。方法模型组、SIRT1激活剂SRT1720低、中、高剂量组(20、40、80mg/kg)建立重度失血性休克/复苏致大鼠急性肾损伤模型,建模成功后SIRT1激活剂SRT1720各剂量组给予相应药物,对照组、模型组给予等体积生理盐水;随后处死大鼠,测定肾/体比值、肌酐(SCr)、尿素氮(BUN)、肾脏SIRT1、信号转导转录激活剂-3(signal transducers and activators of transcription factor 3,STAT3)mRNA和蛋白水平、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。结果与对照组比较,模型组肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α升高(t值分别为25.632、14.524、18.965、23.654、23.654、18.695、19.547,P均<0.001);与模型组比较,SRT1720各剂量组肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α降低(t=21.526、19.654、23.654、25.148,32.654、19.654、21.548、25.965、24.967、28.741、30.365、31.654、23.654、18.475、26.548、29.512,30.248、24.659、24.965、22.698、26.985,P均<0.001),且随着SRT1720给药剂量的增加,肾/体比值、尿蛋白、SCr、BUN、IL-2、IL-6、TNF-α逐渐降低,剂量-效应关系明显(t=38.632、19.625、25.847、27.489、26.954、29.547、32.685、34.489、32.362、24.548、29.654、28.415、35.957、32.548,P均<0.001)。与对照组比较,模型组肾SIRT1 mRNA和蛋白水平降低(t=38.635、32.145,P均<0.001),STAT3 m RNA水平升高(t=32.636、30.213,P均<0.001);与模型组比较,SRT1720各剂量组SIRT1 mRNA和蛋白水平升高(t=18.965、23.147、28.476、30.216、23.654、28.471,P均<0.001),STAT3 mRNA和蛋白水平降低(t=22.654、25.489、29.548、33.265、41.326、29.635,P均<0.001),且随着SRT1720给药剂量增加,SIRT1 m RNA和蛋白水平逐渐升高,STAT3 mRNA和蛋白水平逐渐降低,剂量-效应关系明显(t=27.485、28.459、30.215、29.584、29.654、31.145、32.159、30.269,P均<0.001)。结论SIRT1激活剂SRT1720能减轻重度失血性休克/复苏致大鼠急性肾损伤;其机制与SIRT1激活剂SRT1720通过激活大鼠肾脏中SIRT1表达,抑制STAT3表达进而抑制炎性介质表达有关。
文摘Objective To study the effects of hypotensive resuscitation and larger volume fluid resuscitation on uncontrolled hemorrhagic shock and survival in rats with a standardized massive splenic injury model（MSI）.Methods Following the MSI model,fifty Wistar rats were randomly and equally divided into five groups,group 1:sham-operated group,group 2: shock untreated group,group 3:normal MAP resuscitation group（during acute resuscitation phase MAP was kept at 80 mm Hg）,group 4:Hypotensive resuscitation group（during acute resuscitation phase MAP was kept at（60±5） mm Hg）,and group 5:larger volume fluid resuscitation with hypotensive resuscitation group(during acute resuscitation phase MAP was kept at（60±5） mm Hg,simultaneously infused SNP at 5 μg·kg-1·min-1).Results The mean survival time in group 1～5 was 180 min,73.50 min±8.04 min,114.30 min±31.33 min,146.70 min±28.07 min and 171.60 min±15.74 min respectively.Statistic significances were seen in each group（P<0.05）,except between group 1 and group 5（P=0.0671）.The amount of bleeding in group 2～5（during acute resuscitation phase） was 3.79 ml/kg±1.39 ml/kg、17.41 ml/kg±8.88 ml/kg、8.67 ml/kg±4.59 ml/kg and 10.33 ml/kg±4.31 ml/kg respectively.The loss of blood in group 3 was significantly more than other groups（P<0.05）.Group 4 and 5 enhanced the blood loss significantly compared with group 2（P<0.05）.The histopathologic of liver and renal showed that histopathologic injury is severe in group 3 compared with group 4,and histopathologic injury is not in evidence in group 5.Conclusion Hypotensive resuscitation and adding SNP at proper dose additionally could improve tissue metabolism and prolong survival time during hypotensive resuscitation from uncontrolled hemorrhagic shock.It is a more ideal resuscitation method compared with normal blood pressure resuscitation.
