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茵陈蒿汤和柴苓汤通过水通道蛋白 9 改善胆管结扎大鼠肝纤维化。

The herbal medicines Inchinkoto and Saireito improved hepatic fibrosis via aquaporin 9 in the liver of a rat bile duct ligation model.

机构信息

Department of Pediatric Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan.

Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan.

出版信息

Pediatr Surg Int. 2021 Aug;37(8):1079-1088. doi: 10.1007/s00383-021-04882-6. Epub 2021 Mar 12.

Abstract

OBJECTIVE

To determine if the administration of the Japanese herbal medicines Inchinkoto (ICKT) and Saireito (SRT) ameliorate hepatic fibrosis and derangement of hepatocyte aquaporins (AQPs) following bile duct ligation (BDL) in a rat model of obstructive cholestasis.

MATERIALS AND METHODS

Five groups of Wistar rats were used, and the groups included sham surgery (Sham group), BDL with no treatment (NT group), BDL plus ICKT (ICKT group), BDL plus SRT (SRT group), and BDL plus ICKT and SRT (SRT/ICKT group). Each herbal medicine was administered at 1 g/kg/day on the first postoperative day. The serum levels and various clinical markers were measured with real-time polymerase chain reaction. Staining was used to evaluate the degree of fibrosis and the inflammatory responses.

RESULTS

Serum aspartate aminotransferase and alanine aminotransferase in the ICKT and SRT/ICKT groups were significantly lower than those in the NT group. NF-κB mRNA expression was significantly decreased in the ICKT group and the SRT/ICKT group compared with the NT group. AQP9 mRNA expression was significantly increased in the ICKT group and the SRT/ICKT group compared with the NT group. The degree of Masson's trichrome staining in the SRT/ICKT group was significantly lower than that in the NT group. The degree of NF-κB staining in the SRT/ICKT group was significantly lower than that in the NT, ICKT, or SRT group.

CONCLUSIONS

The postoperative administration of ICKT and SRT induced synergistic beneficial effects, resulting in the reduction of hepatic fibrosis via mechanisms involving the inhibition of NF-κB expression and the improvement of AQP9 downregulation.

摘要

目的

确定日本草药 Inchinkoto(ICKT)和 Saireito(SRT)的给药是否可以改善胆管结扎(BDL)后梗阻性胆汁淤积大鼠模型中的肝纤维化和肝细胞水通道蛋白(AQP)的紊乱。

材料和方法

使用五组 Wistar 大鼠,包括假手术(Sham 组)、无治疗的 BDL(NT 组)、BDL 加 ICKT(ICKT 组)、BDL 加 SRT(SRT 组)以及 BDL 加 ICKT 和 SRT(SRT/ICKT 组)。每种草药均在术后第一天以 1g/kg/天给药。通过实时聚合酶链反应测量血清水平和各种临床标志物。染色用于评估纤维化程度和炎症反应。

结果

ICKT 和 SRT/ICKT 组的血清天冬氨酸转氨酶和丙氨酸转氨酶明显低于 NT 组。与 NT 组相比,ICKT 组和 SRT/ICKT 组的 NF-κB mRNA 表达明显降低。与 NT 组相比,ICKT 组和 SRT/ICKT 组的 AQP9 mRNA 表达明显增加。SRT/ICKT 组的 Masson 三色染色程度明显低于 NT 组。SRT/ICKT 组的 NF-κB 染色程度明显低于 NT、ICKT 或 SRT 组。

结论

术后给予 ICKT 和 SRT 可产生协同有益作用,通过抑制 NF-κB 表达和改善 AQP9 下调来减少肝纤维化。

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