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别嘌醇对大鼠脂肪肝疾病的治疗作用

THE THERAPEUTIC EFFECT OF ALLOPURINOL IN FATTY LIVER DISEASE IN RATS.

作者信息

Barişik V, Korkmaz H A, Çekdemir Y E, Torlak D, Aktuğ H, Yavaşoğlu A, Erbaş O

机构信息

Metropol Medicine Center - Department of Internal Medicine.

"Dr. Behcet Uz" Children's Hospital - Division of Pediatric Endocrinology.

出版信息

Acta Endocrinol (Buchar). 2023 Apr-Jun;19(2):155-162. doi: 10.4183/aeb.2023.155. Epub 2023 Oct 27.

DOI:10.4183/aeb.2023.155
PMID:37908883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10614584/
Abstract

BACKGROUND

Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD).

AIM

We therefore aimed at evaluating the influence of allopurinol on the course of NAFLD in rats.

STUDY DESIGN

We divided 21 mature albino Sprague Dawley rats into three groups: controls (n = 7, normal diet for 12 weeks); NAFLD rat models (by feeding water containing 30% fructose for first 8 weeks) treated with allopurinol subsequently for the next 4 weeks (n = 7); and similar case treated with placebo (saline) subsequently for the next 4 weeks (n = 7).

METHODS

We compared the histopathological scores, IL-1 and IL-2 immunoexpression levels across the groups. Liver histopathological score was determined by observing the steatosis (the percentage of liver cells containing fat): <25% = 1+, 25% - 50% = 2+, 51% - 75% = 3+, >75% = 4+; inflammation and necrosis: 1 focus per low-power field = 1+; and 2 or more foci = 2+. The number of liver IL-1 and IL-2 positive cells was measured by systematically scoring at least 100 hepatocyte cells per field in 10 fields of tissue sections by a magnification of 100.

RESULTS

Xanthine oxidase (XO) activity and lipid peroxidation was significantly different in the allopurinol group compared to the saline group (XO; 0.098 ± 0.006 mU/mg . 0.162 ± 0.008 mU/mg, p = 0.01, 0.116 ± 0.040 nmol malondialdehyde/mg 0.246 ± 0.040 nmol malondialdehyde /mg, p = 0.01). The allopurinol group had lower histopathological scores, IL-1 and IL-2 immunoexpression levels in the liver compared to the saline group (2.13 ± 0.35 against 5.45 ± 0.24, p = 0.003, IL-1; 5.76 ± 0.43 against 12.85 ± 3.26, p = 0.023, IL-2; 8.55 ± 1.14 against 56.23 ± 7.12, p = 0.002).

CONCLUSIONS

Allopurinol has a therapeutic role against the progression of NAFLD of the rats.

摘要

背景

高尿酸血症与非酒精性脂肪性肝病(NAFLD)相关。

目的

因此,我们旨在评估别嘌醇对大鼠非酒精性脂肪性肝病病程的影响。

研究设计

我们将21只成年白化斯普拉格-道利大鼠分为三组:对照组(n = 7,正常饮食12周);非酒精性脂肪性肝病大鼠模型(前8周饮用含30%果糖的水),随后4周用别嘌醇治疗(n = 7);以及类似病例随后4周用安慰剂(生理盐水)治疗(n = 7)。

方法

我们比较了各组的组织病理学评分、白细胞介素-1(IL-1)和白细胞介素-2(IL-2)免疫表达水平。肝脏组织病理学评分通过观察脂肪变性(含脂肪的肝细胞百分比)来确定:<25% = 1+,25% - 50% = 2+,51% - 75% = 3+,>75% = 4+;炎症和坏死:每低倍视野1个病灶 = 1+;2个或更多病灶 = 2+。通过在10个组织切片视野中,以100倍放大倍数系统地对每个视野至少100个肝细胞进行评分,来测量肝脏IL-1和IL-2阳性细胞的数量。

结果

与生理盐水组相比,别嘌醇组的黄嘌呤氧化酶(XO)活性和脂质过氧化有显著差异(XO;0.098±0.006 mU/mg对0.162±0.008 mU/mg,p = 0.01,0.116±0.040 nmol丙二醛/mg对0.246±0.040 nmol丙二醛/mg,p = 0.01)。与生理盐水组相比,别嘌醇组肝脏的组织病理学评分、IL-1和IL-2免疫表达水平较低(2.13±0.35对5.45±0.24,p = 0.003,IL-1;5.76±0.43对12.85±3.26,p = 0.023,IL-2;8.55±1.14对56.23±7.12,p = 0.002)。

结论

别嘌醇对大鼠非酒精性脂肪性肝病的进展具有治疗作用。

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J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3497-e3503. doi: 10.1210/clinem/dgac190.
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A combined association of serum uric acid, alanine aminotransferase and waist circumference with non-alcoholic fatty liver disease: a community-based study.血清尿酸、丙氨酸氨基转移酶和腰围联合与非酒精性脂肪性肝病的相关性:一项基于社区的研究。
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Impact of renaming NAFLD to MAFLD in an Australian regional cohort: Results from a prospective population-based study.澳大利亚区域性队列研究中,将非酒精性脂肪性肝病更名为代谢相关性脂肪性肝病的影响:一项前瞻性基于人群的研究结果。
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Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2.别嘌醇通过激活 Nrf2 改善 1 型糖尿病大鼠的肝损伤。
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