Protective effect of Esmolol for sepsis-induced acute kidney injury in rats

doi:10.3877/cma.j.issn.1674-0785.2021.04.008

Abstract

Abstract:

Objective

To investigate the underlying mechanism of Esmolol to attenuate sepsis-induced acute kidney injury (SAKI).

Methods

Forty-eight male SD rats were randomly and equally divided into a sham operation group (Sham group), a sepsis group (CLP group), and an Esmolol group (ES group). In each group, 16 rats were further randomly divided into either a 6-h group or a 24-h group. Rats in the Sham group received only cecal exploration, and the rats in the CLP and ES groups received the cecal ligation and puncture. When the model was established, internal jugular vein catheterization was performed, and normal saline (1 ml/h) was infused through the internal jugular vein in the Sham and CLP groups, while the ES group was infused with Esmolol [15 mg/(kg·h), 1 ml/h]. After infusing the drug for 6 hours, the rats in each group were sacrificed at 6 h or 24 h after the operation. Blood and kidney tissue samples were collected for further examinations. Serum was isolated by centrifugation to detect the contents of BUN and Cr by ELISA. For kidney tissue samples, left kidney sample was used for p53 immunohistochemical detection, while right kidney sample from the same rat was used for Western blot analysis of the protein expression levels of TLR-4, NF-κB, and ATM, and for ELISA to detect the TIMP-2 and IGFBP-7 level.

Results

(1)TLR-4 and NF-κB in the ES-6 h group and CLP-6 h group were significantly higher than those of the Sham-6 h group (P＜0.05). And these two factors in the CLP-24 h group were also significantly higher than those of the Sham-24 h group (P＜0.05). TLR-4 level in the ES-24 h group was significantly lower than that of the CLP-24 h group (P＜0.05). (2) Serum Cr and BUN in the ES-6 h group and the CLP-6 h group were also significantly higher than those of the Sham group (P＜0.05), but the ES-24 h group showed a decreasing trend compared with the CLP-24 h group (P＜0.05). (3) The levels of IGFBP-7, TIMP-2, ATM, and p53 in the CLP group and ES group were significantly higher than those in the Sham group at each time (P＜0.05), and they were significantly lower in the ES group than in the CLP group (P＜0.05) at each time point.

Conclusion

Esmolol reduces inflammation and renal tubular epithelial cell cycle block, promotes the recovery of renal function in SAKI rats, and thus protects SAKI rats possibly by affecting the expression of key proteins of the TLR-4/NF-κB/ATM/p53 pathway.

Key words: Esmolol, Inflammation, Cell cycle arrest, Sepsis-induced acute kidney injury

Jingzhuo Liu, Li Ma. Protective effect of Esmolol for sepsis-induced acute kidney injury in rats[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(04): 280-287.

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Figures/Tables 3

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