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脓毒症大鼠肝脏葡萄糖代谢相关酶的mRNA编码水平改变。

Altered levels of mRNA encoding enzymes of hepatic glucose metabolism in septic rats.

作者信息

Chang C K, Moskal S F, Srivenugopal K S, Schumer W

机构信息

Department of Surgery, University of Health Sciences, Chicago Medical School, Mount Sinai Hospital Medical Center, Illinois 60608.

出版信息

Circ Shock. 1993 Sep;41(1):35-9.

PMID:8403244
Abstract

We investigated whether the multiple pathophysiological signals generated in a peritonitis septic model alter the mRNA levels of glycolytic and gluconeogenic enzymes, and whether these alterations are associated with glucose dyshomeostasis. Rats were sham-operated in the control group, and peritonitis sepsis was produced by a 1 cm cecal incision in the septic group. At 2, 4, and 6 hr post-surgery, total cellular RNAs were isolated from livers, and Northern blots performed to measure mRNA levels of aldolase B (ADL), lactate dehydrogenase (LDH), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK). Hepatic PEPCK enzymatic activity was measured by condensing 14CO2 with phosphoenolpyruvate (PEP) to form malate. Serum glucose concentrations were also measured. We found the following: At 2 hr of peritonitis sepsis, serum glucose concentrations, mRNA levels of all enzymes, and PEPCK enzymatic activity increased over control levels. At 4 hr of peritonitis sepsis, serum glucose concentrations and mRNA levels of GK and PK continued to increase; mRNA levels of all other enzymes, as well as PEPCK enzymatic activity decreased to or below control levels. At 6 hr of peritonitis sepsis, serum glucose concentrations, mRNA levels of all enzymes, and PEPCK enzymatic activity decreased to or below control levels. We concluded that sepsis affects mRNA levels of glycolytic and gluconeogenic enzymes at the transcriptional level, and that these alterations are associated with glucose dyshomeostasis.

摘要

我们研究了腹膜炎脓毒症模型中产生的多种病理生理信号是否会改变糖酵解和糖异生酶的mRNA水平,以及这些改变是否与葡萄糖稳态失衡有关。对照组大鼠进行假手术,脓毒症组通过盲肠1厘米切口制造腹膜炎脓毒症。术后2、4和6小时,从肝脏中分离总细胞RNA,并进行Northern印迹分析以测量醛缩酶B(ADL)、乳酸脱氢酶(LDH)、丙酮酸激酶(PK)、磷酸烯醇丙酮酸羧激酶(PEPCK)和葡萄糖激酶(GK)的mRNA水平。通过使14CO2与磷酸烯醇丙酮酸(PEP)缩合形成苹果酸来测量肝脏PEPCK酶活性。还测量了血清葡萄糖浓度。我们发现:在腹膜炎脓毒症2小时时,血清葡萄糖浓度、所有酶的mRNA水平和PEPCK酶活性均高于对照水平。在腹膜炎脓毒症4小时时,血清葡萄糖浓度以及GK和PK的mRNA水平继续升高;所有其他酶的mRNA水平以及PEPCK酶活性降至或低于对照水平。在腹膜炎脓毒症6小时时,血清葡萄糖浓度、所有酶的mRNA水平和PEPCK酶活性降至或低于对照水平。我们得出结论,脓毒症在转录水平上影响糖酵解和糖异生酶的mRNA水平,并且这些改变与葡萄糖稳态失衡有关。

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