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经免疫组化和 qRT-PCR 证实,水飞蓟宾在大鼠肝缺血/再灌注模型中具有肝保护作用。

The hepatoprotective effect of silibinin after hepatic ischemia/reperfusion in a rat model is confirmed by immunohistochemistry and qRT-PCR.

机构信息

Postgraduate Program in Hepatobiliary/Pancreatic Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

Laboratory of Histology-Embryology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.

出版信息

J Pharm Pharmacol. 2021 Aug 12;73(9):1274-1284. doi: 10.1093/jpp/rgab062.

Abstract

OBJECTIVES

We investigated the positive effect of silibinin after IV administration as silibinin-hydroxypropyl-β-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2.

METHODS

63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-β-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min).

KEY FINDINGS

qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases ( matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression.

CONCLUSIONS

Silibinin may have a beneficial effect on the protection of the liver.

摘要

目的

通过测量肿瘤坏死因子-α、白细胞介素-6、单核细胞趋化蛋白-1、基质金属蛋白酶和基质金属蛋白酶组织抑制剂-2 的基因表达和肝组织蛋白水平,研究静脉给予水飞蓟素-羟丙基-β-环糊精冻干产品后水飞蓟素的积极作用。

方法

63 只年龄为 13.24±4.40 周的 Wistar 大鼠进行肝缺血/再灌注(I/R)损伤。动物随机分为三组:假手术组(S;n=7);对照组(C;n=28);水飞蓟素组(Si;n=28)。C 组和 Si 组在 45 分钟时发生缺血。Si 组在再灌注前立即静脉注射 5mg/kg 的水飞蓟素-羟丙基-β-环糊精。根据安乐死时间(即 60、120、180 和 240 分钟),两组进一步分为 4 个亚组。

主要发现

qRT-PCR 结果证实,在 I/R 损伤后 240 分钟,促炎因子(肿瘤坏死因子-α:P<0.05;MCR1:P<0.05)和基质金属蛋白酶(基质金属蛋白酶 2:P<0.05;基质金属蛋白酶 3:P<0.05)的表达以及 Si 组肝组织中基质金属蛋白酶组织抑制剂-2 的表达显著降低。此外,免疫组化水平的结果证实,在 240 分钟时,促炎因子(肿瘤坏死因子-α:P<0.05;MCR1:P<0.05)和基质金属蛋白酶(基质金属蛋白酶 2:P<0.05;基质金属蛋白酶 3:P<0.05)在 Si 组的表达明显较低,而基质金属蛋白酶组织抑制剂-2 的表达较高。

结论

水飞蓟素可能对肝脏保护具有有益作用。

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