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富含水解乳清肽的肠内营养对大鼠肝脏温热缺血/再灌注损伤的有益作用。

Beneficial effects of enteral nutrition containing with hydrolyzed whey peptide on warm ischemia/reperfusion injury in the rat liver.

机构信息

Department of Surgery, The University of Tokushima, Tokushima, Japan.

出版信息

Hepatol Res. 2014 Jan;44(1):114-21. doi: 10.1111/hepr.12097. Epub 2013 Apr 12.

Abstract

AIM

This study examined the efficacy of enteral nutrition containing hydrolyzed whey peptide (HWP) on warm ischemia/reperfusion (I/R) injury in the rat liver.

METHODS

Male Wistar rats were subjected to 30 min of warm hepatic ischemia followed by immediate p.o. intake of enteral nutrition with WHP (HWP group) or 20% glucose solution (control group) (0.025 mL/g). The animals were killed at 6 or 12 h after reperfusion. The serum aspartate aminotransferase (AST) and alanine aminotransferase alt (ALT) levels were measured. The necrotic areas were assessed histologically. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activation were assessed to evaluate apoptosis. The expressions of hepatic tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nuclear factor (NF)-κB in the liver tissue were assessed by real time reverse transcription polymerase chain reaction.

RESULTS

Significant reductions in the serum AST and ALT levels were seen in the HWP group compared with the control group at both 6 and 12 h after reperfusion. The necrotic areas and numbers of TUNEL positive cells were significantly decreased in the HWP group at 6 and 12 h after reperfusion. The caspase-3/7 activities were significantly decreased in HWP group at 6 and 12 h after reperfusion. The mRNA expressions of TNF-α and IL-6 were significantly reduced in the HWP group at 12 h after reperfusion. NF-κB mRNA expression was significantly increased in the HWP group at 6 and 12 h after reperfusion.

CONCLUSION

Enteral nutrition containing HWP ameliorated the hepatic warm I/R injury possibly through the suppression of pro-inflammatory cytokine expressions and the induction of NF-κB in the rat liver.

摘要

目的

本研究旨在探讨含有水解乳清肽(HWP)的肠内营养对大鼠肝脏热缺血/再灌注(I/R)损伤的疗效。

方法

雄性 Wistar 大鼠接受 30 分钟的热肝缺血,然后立即口服含有 HWP(HWP 组)或 20%葡萄糖溶液(对照组)的肠内营养(0.025 mL/g)。动物在再灌注后 6 或 12 小时处死。测定血清天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶 alt(ALT)水平。评估组织学坏死面积。末端脱氧核苷酸转移酶 dUTP 缺口末端标记(TUNEL)染色和 caspase-3 活化用于评估细胞凋亡。通过实时逆转录聚合酶链反应评估肝组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和核因子(NF)-κB 的表达。

结果

与对照组相比,再灌注后 6 和 12 小时,HWP 组血清 AST 和 ALT 水平显著降低。再灌注后 6 和 12 小时,HWP 组坏死面积和 TUNEL 阳性细胞数明显减少。再灌注后 6 和 12 小时,HWP 组 caspase-3/7 活性明显降低。再灌注后 12 小时,HWP 组 TNF-α和 IL-6 的 mRNA 表达明显降低。再灌注后 6 和 12 小时,HWP 组 NF-κB mRNA 表达明显增加。

结论

含有 HWP 的肠内营养通过抑制大鼠肝脏促炎细胞因子的表达和诱导 NF-κB,改善了肝脏热缺血再灌注损伤。

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