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肝缺血再灌注模型中的短期丙氨酰谷氨酰胺二肽预处理:对大鼠微循环和抗氧化状态的影响

Short-term alanyl-glutamine dipeptide pretreatment in liver ischemia-reperfusion model: effects on microcirculation and antioxidant status in rats.

作者信息

Szijártó Attila, Hahn Oszkár, Batmunkh Enkhjargal, Stangl Rita, Kiss András, Lotz Gábor, Schaff Zsuzsa, Váli László, Blázovics Anna, Gero Domokos, Szabó Csaba, Kupcsulik Péter, Harsányi László

机构信息

1st Department of Surgery, Semmelweis University, Budapest, Hungary.

出版信息

Clin Nutr. 2007 Oct;26(5):640-8. doi: 10.1016/j.clnu.2007.06.011. Epub 2007 Aug 8.

DOI:10.1016/j.clnu.2007.06.011
PMID:17689840
Abstract

BACKGROUND & AIMS: Ischemia-reperfusion (I-R) injury is responsible for the morbidity associated with liver surgery. Production of toxic free radicals influences the microcirculation. The aim of our study was to examine the effect of glutamine (Gln) supplementation--adminstered in alanyl-glutamine dipeptide form--on liver function, immuno/histopathology and the oxidative state of the liver after injury.

METHODS

Two-hundred and fifty grams male Wistar rats underwent normothermic, 60 min, segmental liver ischemia followed by 6 h of reperfusion. The animals (n = 45) were divided into three groups: sham operated, I-R and parenteral Gln pretreatment. Hepatic microcirculation was monitored by laser Doppler flowmetry. At the 6 h of reperfusion, histological alterations, TUNEL reaction, active caspase-3 reaction, serum and liver tissue antioxidant levels, serum ALAT, ASAT and TNF-alpha levels were measured.

RESULTS

Upon reperfusion, the Gln group had significantly (p<0.05) higher flow rates than the I-R group and, at the end of the 6h of reperfusion, significantly (p<0.05) lower serum ALAT and ASAT levels. The liver chemiluminescent intensity was lower, free SH-groups were elevated, while the reducing power was decreased in the Gln-pretreated group. Positive staining for caspase-3 after Gln pretreatment was significantly increased in contrast to the control tissues.

CONCLUSION

Glutamine pretreatment is beneficial in supporting hepatic microcirculation and can prevent hepatocellular necrosis in liver reperfusion injury.

摘要

背景与目的

缺血再灌注(I-R)损伤是肝脏手术相关发病的原因。有毒自由基的产生会影响微循环。我们研究的目的是检测以丙氨酰谷氨酰胺二肽形式补充谷氨酰胺(Gln)对损伤后肝脏功能、免疫/组织病理学及肝脏氧化状态的影响。

方法

250克雄性Wistar大鼠接受常温下60分钟的节段性肝脏缺血,随后再灌注6小时。将动物(n = 45)分为三组:假手术组、I-R组和肠外Gln预处理组。通过激光多普勒血流仪监测肝脏微循环。在再灌注6小时时,测量组织学改变、TUNEL反应、活性半胱天冬酶-3反应、血清和肝组织抗氧化水平、血清谷丙转氨酶(ALAT)、谷草转氨酶(ASAT)和肿瘤坏死因子-α(TNF-α)水平。

结果

再灌注时,Gln组的血流速度显著高于I-R组(p<0.05),且在再灌注6小时结束时,血清ALAT和ASAT水平显著低于I-R组(p<0.05)。Gln预处理组的肝脏化学发光强度较低,游离巯基升高,而还原能力降低。与对照组织相比,Gln预处理后半胱天冬酶-3的阳性染色显著增加。

结论

谷氨酰胺预处理有助于支持肝脏微循环,并可预防肝脏再灌注损伤中的肝细胞坏死。

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