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长链多不饱和脂肪酸对大鼠肝肾综合征的保护作用。

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats.

作者信息

Duailibe João Bruno Beretta, Viau Cassiana Macagnan, Saffi Jenifer, Fernandes Sabrina Alves, Porawski Marilene

机构信息

Department of Hepatology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil.

Department of Basic Health Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, Brazil.

出版信息

World J Nephrol. 2024 Sep 25;13(3):95627. doi: 10.5527/wjn.v13.i3.95627.

Abstract

BACKGROUND

Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS.

AIM

To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats.

METHODS

Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with ≤ 0.05.

RESULTS

Omega-3 significantly decreased the production of reactive oxygen species ( < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 ( < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group ( < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential ( < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group ( > 0.05) were observed.

CONCLUSION

The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.

摘要

背景

肝肾综合征(HRS)是肝硬化患者中最常见的急性肾损伤形式。其特征为肾血流量减少,是晚期肝硬化患者最严重的并发症。先前的研究表明,抗氧化剂可延缓肝硬化患者高动力循环状态的发生,并改善HRS患者的肾功能。定期补充ω-3可显著降低肝病风险。这种补充剂可能是HRS患者的一种额外治疗方法。

目的

评估补充ω-3多不饱和脂肪酸对肝硬化大鼠肾脏的抗氧化作用。

方法

通过胆管结扎(BDL)诱导大鼠继发性胆汁性肝硬化28天。我们将24只雄性Wistar大鼠分为以下几组:I组(对照组);II组(用ω-3治疗,1 g/kg体重);III组(BDL并用ω-3治疗,1 g/kg体重);IV组(BDL未治疗)。通过过量麻醉处死动物;解剖并取出肾脏,在液氮中冷冻,然后储存在-80℃的冰箱中以备后续分析。我们评估了肾脏中的氧化应激、一氧化氮(NO)代谢产物、彗星试验检测的DNA损伤、细胞活力测试和细胞凋亡。数据通过单因素方差分析进行分析,并使用Tukey检验比较均值,P≤0.05。

结果

ω-3显著降低了用ω-3治疗的肝硬化大鼠肾脏中的活性氧生成(P<0.001)和脂质过氧化(P<0.001)。与BDL组相比,BDL+ω-3组中抗氧化酶超氧化物歧化酶和过氧化氢酶的活性增加(P<0.01)。在ω-3治疗的BDL组中,NO生成、DNA损伤和caspase-9裂解显著降低。与BDL相比,用ω-3治疗的BDL组中线粒体电化学电位增加(P<0.001)。与对照组相比,ω-3治疗的HRS组中细胞存活指数没有变化(P>0.05)。

结论

该研究表明,ω-3可通过增加抗氧化酶、抑制自由基形成和减少细胞凋亡来保护细胞完整性和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86e8/11439093/ea01664d10ea/95627-g001.jpg

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