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. 2017 Mar 29:12:593-602.
doi: 10.2147/CIA.S132277. eCollection 2017.

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats

Chao Liu  1 , Jie Hu  1 , Zhi Mao  1 , Hongjun Kang  1 , Hui Liu  1 , Wanlei Fu  2 , Yangfan Lv  2 , Feihu Zhou  1
Affiliations

Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats

Chao Liu et al. Clin Interv Aging. .

Abstract

Background: Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.

Objective: To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats.

Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model.

Results: The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, P<0.05 at 12 h and 24 h post-CLP). The rate of severe AKI (RIFLE-F) at 24 h post-CLP was 43% for both the control and L d-gal groups and 80% for the H d-gal group.

Conclusion: High-dose- d-gal-induced aging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

Keywords: acute kidney injury; aging rat; cecal ligation and puncture; d-galactose; inflammatory response.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Survival of septic rats from the three groups. Notes: H d-gal vs control P=0.022; H d-gal vs L d-gal P=0.059; L d-gal vs control P=0.689. Abbreviations: d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal.
Figure 2
Figure 2
Serum MDA and SOD levels in the three groups. Notes: MDA and SOD were measured before CLP. *P<0.05. Abbreviations: CLP, cecal ligation and puncture; d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal; MDA, malondialdehyde; SOD, superoxide dismutase.
Figure 3
Figure 3
Renal function in septic rats of the three groups. Notes: (A) Serum Cr concentration. (B) BUN concentration. (C) Severity of AKI 12 h post-CLP. (D) Severity of AKI 24 h post-CLP. AKI was measured based on RIFLE categories. R, I, F = AKI RIFLE classes risk (creatinine change, 150%–199%), injury (creatinine change, 200%–299%), and failure (creatinine change, ≥300%). Data are shown as the mean ± standard error. *P<0.05 compared with the control group. #P<0.05 compared with the L d-gal group. Abbreviations: CLP, cecal ligation and puncture; d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal; Cr, creatinine; BUN, blood urea nitrogen; AKI, acute kidney injury.
Figure 4
Figure 4
Plasma cytokine levels in septic rats of the three groups. Notes: (A) Plasma NGAL. (B) Plasma IL-6. (C) Plasma IL-10. (D) Plasma TNF-α. *P<0.05 compared with the control group. #P<0.05 compared with the L d-gal group. Abbreviations: CLP, cecal ligation and puncture; d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal; NGAL, neutrophil gelatinse-associated lipocalin; IL, interleukin; TNF, tumor necrosis factor.
Figure 5
Figure 5
Expression of miRNA-155 in septic rats of the three groups. Note: *P<0.05. Abbreviations: CLP, cecal ligation and puncture; d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal.
Figure 6
Figure 6
Kidney histopathology in septic rats of the three groups. Notes: (A) Control group 12 h post-CLP. (B) Control group 24 h post-CLP. (C) L d-gal group 12 h post-CLP. (D) L d-gal group 24 h post-CLP. (E) H d-gal group 12 h post-CLP. (F) H d-gal group 24 h post-CLP. Abbreviations: CLP, cecal ligation and puncture; d-gal, d-galactose; H d-gal, high-dose d-gal; L d-gal, low-dose d-gal.
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