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右美托咪定通过 PI3K/Akt/HIF-1α 信号通路促进肾缺血再灌注损伤大鼠肾功能恢复,降低炎症水平。

Dexmedetomidine promotes the recovery of renal function and reduces the inflammatory level in renal ischemia-reperfusion injury rats through PI3K/Akt/HIF-1α signaling pathway.

机构信息

Department of Anesthesiology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Dec;24(23):12400-12407. doi: 10.26355/eurrev_202012_24035.

Abstract

OBJECTIVE

To evaluate the protective effect of dexmedetomidine (Dex) against renal ischemia-reperfusion injury (RIRI) in rats through the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway.

MATERIALS AND METHODS

(1) A Sprague- Dawley rat model of RIRI was established. Thirty rats were divided into Sham group, injury (RIRI) group, and Dex treatment (RIRI + Dex) group. Serum was collected to detect renal function-related indexes, and the levels of serum inflammatory factors were examined via enzyme-linked immunosorbent assay (ELISA). (2) The kidney tissues were separated, and the degree of tissue damage was determined using immunohistochemical staining. (3) Ribonucleic acids (RNAs) were extracted from tissues, and the mRNA levels of inflammatory factors were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). (4) The protein expressions of Akt, phosphorylated (p)-Akt, PI3K, p-PI3K, and HIF-1α were detected via Western blotting.

RESULTS

Compared with those in RIRI group, the levels of blood urea nitrogen and creatinine declined (p<0.05), the synthesized mRNAs of inflammatory factors in the kidney tissues were reduced (p<0.05), the secreted serum inflammatory factors was also reduced (p<0.05), and the phosphorylation levels of Akt and PI3K and the HIF-1α level rose (p<0.05) in RIRI + Dex group.

CONCLUSIONS

Dex promotes the recovery of renal function and reduces the inflammatory level in RIRI rats through the PI3K/Akt/HIF-1α signaling pathway.

摘要

目的

通过磷脂酰肌醇 3-羟激酶(PI3K)/蛋白激酶 B(Akt)/缺氧诱导因子-1α(HIF-1α)信号通路评估右美托咪定(Dex)对大鼠肾缺血再灌注损伤(RIRI)的保护作用。

材料与方法

(1)建立 Sprague-Dawley 大鼠 RIRI 模型。30 只大鼠分为假手术(Sham)组、损伤(RIRI)组和 Dex 治疗(RIRI+Dex)组。收集血清以检测肾功能相关指标,并通过酶联免疫吸附测定(ELISA)检测血清炎症因子水平。(2)分离肾脏组织,通过免疫组织化学染色测定组织损伤程度。(3)提取组织中的核糖核酸(RNA),使用定量逆转录聚合酶链反应(qRT-PCR)测量炎症因子的 mRNA 水平。(4)通过 Western 印迹检测 Akt、磷酸化(p)-Akt、PI3K、p-PI3K 和 HIF-1α的蛋白表达。

结果

与 RIRI 组相比,RIRI+Dex 组血尿素氮和肌酐水平下降(p<0.05),肾脏组织中炎症因子的合成 mRNA 减少(p<0.05),血清中炎症因子的分泌也减少(p<0.05),Akt 和 PI3K 的磷酸化水平以及 HIF-1α 水平升高(p<0.05)。

结论

Dex 通过 PI3K/Akt/HIF-1α 信号通路促进 RIRI 大鼠肾功能的恢复,降低炎症水平。

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