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miR-26b 通过靶向 hENT1 依赖 RhoA/ROCK-1 通路对肝硬化门静脉高压大鼠肝硬化和门静脉压的影响。

Influence of miR-26b on hepatic cirrhosis and portal pressure in rats with cirrhotic portal hypertension by targeting hENT1 depending on RhoA/ROCK-1 pathway.

机构信息

Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1668-1673. doi: 10.26355/eurrev_201902_17128.

Abstract

OBJECTIVE

To explore the regulatory effect of micro ribonucleic acid-26b (miR-26b) on rat models of cirrhotic portal hypertension and the underlying mechanism of action.

MATERIALS AND METHODS

Common bile duct ligation (BDL) was applied to establish rat models. A total of 30 male Wistar rats were randomly divided into sham operation group (Sham group), operation group (BDL group) and miR-26b intervention group (miR-26b mimic group). Hematoxylin-eosin (HE) staining assay was performed to detect pathological characteristics of rat liver tissues in each group. The portal venous pressure in each group was then determined. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rat serum were measured via serological test. Kits were used to detect serum levels of hyaluronic acid (HA), procollagen III peptide (PCIII) and laminin (LN) in rats. Western blotting was utilized to detect the protein levels of human equilibrative nucleoside transporter 1 (hENT1), ras homolog gene family, member A (RhoA) and Rho-associated coiled-coil-containing kinase protein-1 (Rock-1).

RESULTS

In comparison with Sham group, BDL group had significantly increased portal venous pressure and protein levels of hENT1, RhoA and ROCK-1, and elevated levels of AST, ALT, HA, PCIII and LN in rats. Compared with those in BDL group, the portal venous pressure and protein levels of hENT1, RhoA and ROCK-1 were overtly reduced, while the levels of AST, ALT, HA, PCIII and LN declined in miR-26b mimic group.

CONCLUSIONS

MiR-26b mimics played a role in the treatment of rats with cirrhotic portal hypertension by targeting hENT1 to inhibit the RhoA/ROCK-1 signaling pathway.

摘要

目的

探讨微小 RNA-26b(miR-26b)对肝硬化门脉高压大鼠模型的调节作用及其作用机制。

材料与方法

采用胆总管结扎(BDL)法建立大鼠模型。将 30 只雄性 Wistar 大鼠随机分为假手术组(Sham 组)、手术组(BDL 组)和 miR-26b 干预组(miR-26b 模拟组)。HE 染色法检测各组大鼠肝组织的病理特征。然后测定各组大鼠的门静脉压力。血清学试验检测大鼠血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平。试剂盒检测大鼠血清中透明质酸(HA)、III 型前胶原肽(PCIII)和层粘连蛋白(LN)水平。Western blot 检测人核苷转运蛋白 1(hENT1)、Rho 相关卷曲螺旋蛋白激酶 1(Rock-1)蛋白水平。

结果

与 Sham 组相比,BDL 组大鼠门静脉压力和 hENT1、RhoA、Rock-1 蛋白水平显著升高,AST、ALT、HA、PCIII 和 LN 水平明显升高。与 BDL 组相比,miR-26b 模拟组大鼠门静脉压力和 hENT1、RhoA、Rock-1 蛋白水平明显降低,AST、ALT、HA、PCIII 和 LN 水平降低。

结论

miR-26b 模拟物通过靶向 hENT1 抑制 RhoA/ROCK-1 信号通路,在治疗肝硬化门脉高压大鼠中发挥作用。

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