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. 2019 Mar;23(1):341-348.
doi: 10.1007/s11325-018-1720-9. Epub 2018 Sep 15.

Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model

Xiao-Bin Zhang  1   2   3   4   5 , Jing-Huang Cai  1   2 , Yu-Yun Yang  1   2 , Yi-Ming Zeng  6   7   8 , Hui-Qing Zeng  9   10 , Miao Wang  1   2 , Xiao Cheng  1   2 , Xiongbiao Luo  11 , Henry Chidozie Ewurum  11
Affiliations

Telmisartan attenuates kidney apoptosis and autophagy-related protein expression levels in an intermittent hypoxia mouse model

Xiao-Bin Zhang et al. Sleep Breath. 2019 Mar.

Erratum in

Abstract

Purpose: Obstructive sleep apnea (OSA) is associated with renal impairs. As a novel pathophysiological hallmark of OSA, chronic intermittent hypoxia (CIH) enhances apoptosis and autophagy. The present study aims to evaluate the effect of telmisartan on CIH-induced kidney apoptosis and autophagy in a mouse model of OSA.

Materials and methods: Mice were randomly allocated to normoxia, CIH, and CIH+telmisartan groups (n = 12 in each group). The CIH exposure duration was 12 weeks. Mice in the CIH+telmisartan group received telmisartan administration. The terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax and cleaved caspase-3 were conducted for evaluating apoptosis in kidney tissue. While the autophagy-related proteins, beclin-1 and LC3, were also observed via western blotting.

Results: The percentage of apoptotic cell in the CIH group was significantly higher than that of normoxia group; meanwhile, Bax and cleaved caspase-3 protein levels were increased in the CIH group than those of normoxia group (all p < 0.05). Compared with the normoxia group, mice in the CIH group had greater autophagy-related proteins (beclin-1 and LC3) expression. When compared to the CIH group, both the renal apoptosis and autophagy in the CIH+telmisartan group were decreased.

Conclusion: The CIH accelerates renal apoptosis and autophagy levels. Telmisartan ameliorating those levels suggests that it might prevent renal impairs from the CIH in OSA patients.

Keywords: Apoptosis; Autophagy; Intermittent hypoxia; Renal; Telmisartan.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Body weight in each group. Mice in the normoxia group were significantly heavier than those in the CIH and CIH+telmisartan groups at the twelfth week of the experimental period. *p < 0.001 when compared with the normoxia group. CIH chronic intermittent hypoxia
Fig. 2
Fig. 2
Western blotting for AGTR1 protein expression. The AGTR1 protein levels in the CIH group significantly increased when compared to the normoxia group (p < 0.05). Treatment with telmisartan obviously decreased the AGTR1 expression in kidney tissue (compared to the CIH group, p < 0.001). AGTR1 angiotensin II receptor type 1, CIH chronic intermittent hypoxia
Fig. 3
Fig. 3
Kidney histopathological changes. The HE staining results illustrated that no abnormal architecture was found in all groups. CIH chronic intermittent hypoxia, HE hematoxylin and eosin staining
Fig. 4
Fig. 4
Effect of telmisartan on apoptosis induced by CIH. The percentage of apoptotic cells (mostly tubular cells) was significantly higher in the CIH group than that of the normoxia group. After treating with telmisartan, the apoptotic percentage in the CIH+telmisartan group was lower than that of the CIH group (A). Mice in the CIH group had higher Bax (B) and cleaved caspase-3 (C) protein levels than those in the normoxia group. In comparison to the CIH group, these proteins levels were decreased in the CIH+telmisartan group (B, C). ***p < 0.001 when compared with normoxia group; *p < 0.05 when compared with normoxia group; ###p < 0.001 when compared with the CIH group; ##p < 0.01 when compared with the CIH group. CIH chronic intermittent hypoxia
Fig. 5
Fig. 5
Effect of telmisartan on autophagy induced by CIH. Western blotting results showed that the beclin-1 levels were higher in the CIH group than those of normoxia group, while the levels were decreased after mice received telmisartan treatment (Fig. 5 A, B); CIH induced high expression of LC3, while telmisartan can attenuate LC3 expression (Fig. 5 C, D). ***p < 0.001 when compared with normoxia group; ##p < 0.01 when compared with the CIH group; ###p < 0.001 when compared with the CIH group. CIH chronic intermittent hypoxia
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