Background

Apelin and its receptor angiotensin receptor - like 1 (APJ) are closely related to renal fibrosis, but their specific roles in renal fibrosis are still controversial. In this article, we discussed the role of Apelin/APJ system in renal fibrosis and its mechanism.

Methods

Chronic intermittent hypoxia (CIH) rat model was established to induce the environment of renal fibrosis and a competitive antagonist of the APJ receptor ML221 was administered to CIH rats. The rats were divided into Control, CIH and ML221 groups. HE staining was used to detect the inflammatory injury and fibrosis of renal tissue. The expressions of renal fibrosis-related indicators transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and Human type I collagen (Col-Ⅰ) were detected by immunohistochemistry. The levels of oxidative stress indexes reactive oxygen species (ROS), Malondialdehyde (MDA), Superoxide Dismutase (SOD) and inflammation-related indexes Interleukin (IL) −6, tumor necrosis factor-α (TNF-α) and IL-1β were detected by ELISA. At the same time, the levels of Apelin-13 and AngiotensinII (AngⅡ) were also measured by ELISA. Finally, western blot was used to detect the expression of Apelin pathway and renal fibrosis-related proteins. In addition, at the cellular level, we divided the cells into Control, CIH, Apelin-13 and Apelin-13+ML-221 groups to further verify the specific mechanisms at the cellular level.

Results

The expression of Apeline-13 and its related pathways was significantly increased after the induction of CIH in rats. However, the degree of renal fibrosis in ML221 group was further significantly increased after inhibiting the expression of Apelin. At the cellular level, CIH model cells treated with Apelin-13 significantly reduced cell proliferation, oxidative stress and inflammatory response, and decreased the expression of fibrosis-related proteins, which can be reversed by ML221 administration.

Conclusion

The increased reactivity of Apelin may be one of the protective mechanisms against renal fibrosis induced by CIH.

中文翻译：

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Apelin 反应活性升高抑制慢性间歇性缺氧诱导的肾纤维化

 背景

Apelin及其受体血管紧张素受体样1（APJ）与肾纤维化密切相关，但其在肾纤维化中的具体作用仍存在争议。本文讨论Apelin/APJ系统在肾纤维化中的作用及其机制。

 方法

建立慢性间歇性缺氧（CIH）大鼠模型，诱导肾纤维化环境，并给予CIH大鼠竞争性APJ受体ML221拮抗剂。将大鼠分为对照组、CIH组和ML221组。 HE染色检测肾组织炎症损伤及纤维化情况。免疫组化法检测肾纤维化相关指标转化生长因子-β（TGF-β）、α-平滑肌肌动蛋白（α-SMA）、人Ⅰ型胶原（Col-Ⅰ）的表达。氧化应激指标活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)以及炎症相关指标白细胞介素(IL)−6、肿瘤坏死因子-α(TNF-α)、IL-1β的水平通过ELISA检测。同时采用ELISA法检测Apelin-13、血管紧张素II（AngⅡ）的水平。最后采用Western blot检测Apelin通路及肾纤维化相关蛋白的表达量。此外，在细胞水平上，我们将细胞分为Control组、CIH组、Apelin-13组和Apelin-13+ML-221组，以进一步在细胞水平上验证具体机制。

 结果

大鼠CIH诱导后Apeline-13及其相关通路的表达显着增加。但抑制Apelin表达后，ML221组肾纤维化程度进一步显着加重。在细胞水平上，用Apelin-13处理的CIH模型细胞显着降低了细胞增殖、氧化应激和炎症反应，并降低了纤维化相关蛋白的表达，这一现象可以通过ML221给药来逆转。

 结论

Apelin 反应性增加可能是对抗 CIH 诱导的肾纤维化的保护机制之一。