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参附汤可通过调节脓毒症大鼠肠上皮紧密连接蛋白和 p-VASP 的表达改善肠通透性。

Shen-Fu Decoction could ameliorate intestinal permeability by regulating the intestinal expression of tight junction proteins and p-VASP in septic rats.

机构信息

Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

出版信息

J Ethnopharmacol. 2021 Mar 25;268:113562. doi: 10.1016/j.jep.2020.113562. Epub 2020 Nov 18.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Shen-Fu Decoction (SFD), a classic Traditional Chinese paired herb formulation, has been widely used for the treatment of sepsis in China. This study was carried out to assess the effects of SFD in sepsis-induced intestinal permeability and intestinal epithelial tight junction damage in rats with sepsis.

MATERIALS AND METHODS

A rat model of sepsis was created by cecal ligation and puncture (CLP). Rats in Sham and CLP + vehicle groups received equal distilled water, while rats in SFD group were treated by gavage of SFD (3 mg/kg, twice a day) for 72h. Mortality, sepsis-induced peritoneal inflammation, intestinal and liver histopathology damage, intestinal permeability (serum FITC-dextran and D-lactate), serum LPS, serum inflammation (PCT, TNF-α, and IL-6), and liver function (AST and ALT) were evaluated. The levels of zonula occluden (ZO-1), Occludin, Claudin-1 were analyzed by Real-time quantitative PCR and Western blotting (WB) respectively. Vasodilator-stimulated phosphoprotein (VASP) and p-VASP in intestinal epithelium were analyzed by WB.

RESULTS

Our study showed that SFD markedly reduced the mortality rate of CLP rats, prevented intestine and liver damage, relieved sepsis-induced intestinal permeability and inflammation elevation, ameliorated sepsis-induced impaired intestinal permeability by regulating the expression of ZO-1, Occludin, Claudin-1 and p-VASP.

CONCLUSIONS

The herbal formula SFD may be useful for reducing sepsis-induced organic damage and mortality by ameliorating the condition of sepsis-induced intestinal permeability by regulating tight junction proteins and p-VASP.

摘要

民族药理学相关性

参附汤(SFD)是一种经典的中药对药配方,已广泛用于中国脓毒症的治疗。本研究旨在评估 SFD 对脓毒症大鼠肠道通透性和肠道上皮紧密连接损伤的影响。

材料与方法

采用盲肠结扎穿孔(CLP)法建立脓毒症大鼠模型。假手术(Sham)和 CLP+vehicle 组大鼠给予等量蒸馏水,SFD 组大鼠给予 SFD(3mg/kg,每日两次)灌胃 72h。评估死亡率、脓毒症引起的腹膜炎症、肠道和肝脏组织病理学损伤、肠道通透性(血清 FITC-右旋糖酐和 D-乳酸)、血清 LPS、血清炎症(PCT、TNF-α和 IL-6)和肝功能(AST 和 ALT)。实时定量 PCR 和 Western blot(WB)分别分析紧密连接蛋白(ZO-1、Occludin 和 Claudin-1)的水平。通过 WB 分析肠道上皮中的血管扩张刺激磷蛋白(VASP)和 p-VASP。

结果

本研究表明,SFD 显著降低了 CLP 大鼠的死亡率,防止了肠和肝损伤,缓解了脓毒症引起的肠道通透性和炎症升高,通过调节 ZO-1、Occludin、Claudin-1 和 p-VASP 的表达,改善了脓毒症引起的肠道通透性受损。

结论

SFD 可能通过调节紧密连接蛋白和 p-VASP 改善脓毒症引起的肠道通透性,从而减少脓毒症引起的器官损伤和死亡率。

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