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2016 ; 129
(9
): 1100-7
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Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by
Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis
#MMPMID27098797
Zhao YL
; Zhang L
; Yang YY
; Tang Y
; Zhou JJ
; Feng YY
; Cui TL
; Liu F
; Fu P
Chin Med J (Engl)
2016[May]; 129
(9
): 1100-7
PMID27098797
show ga
BACKGROUND: Resolvin D1 (RvD1) is a newly found anti-inflammatory bioactive
compound derived from polyunsaturated fatty acids. The current study aimed to
explore the protective effect of RvD1 on lipopolysaccharide (LPS)-induced acute
kidney injury (AKI) and its possible mechanism. METHODS: Both in vivo and in
vitro studies were conducted. Male BALB/c mice were randomly divided into control
group (saline), LPS group (LPS 5 mg/kg), RvD1 group (RvD1 5 ?g/kg + LPS 5 mg/kg),
and blockage group (Boc-MLP 5 ?g/kg + RvD1 5 ?g/kg + LPS 5 mg/kg). Boc-MLP is a
RvD1 receptor blocker. The mice were intraperitoneally injected with these drugs
and recorded for general condition for 48 h, while the blood and kidneys were
harvested at 2, 6, 12, 24, and 48 h time points, respectively (n = 6 in each
group at each time point). Human proximal tubule epithelial cells (HK-2) were
randomly divided into control group (medium only), LPS group (LPS 5 ?g/ml), RvD1
group (RvD1 10 ng/ml + LPS 5 ?g/ml), and blockage group (Boc-MLP 10 ng/ml + RvD1
10 ng/ml + LPS 5 ?g/ml). The cells were harvested for RNA at 2, 4, 6, 12, and 24
h time points, respectively (n = 6 in each group at each time point). Blood
creatinine was tested by using an Abbott i-STAT portable blood gas analyzer.
Tumor necrosis factor-? (TNF-?) level was detected by ELISA. Kidney pathology was
observed under hematoxylin and eosin (HE) staining and transmission electron
microscope (TEM). We hired immune-histological staining, Western blotting, and
fluorescence quantitative polymerase chain reaction to detect the expression of
RvD1 receptor ALX, nuclear factor-kappa B (NF-?B) signaling pathway as well as
caspase-3. Kidney apoptosis was evaluated by TUNEL staining. RESULTS: RvD1
receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis
indicated that RvD1 improved 48 h animal survival (80%) compared with LPS group
(40%) and RvD1 blockage group (60%), while RvD1 also ameliorated kidney
pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA
expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-?
in both mice kidneys and HK-2 cells were all up-regulated, while RvD1
substantially inhibited the up-regulation of these genes. Western blotting showed
that the phosphorylated-I?B/I?B ratio in LPS group was significantly higher than
that in the control group, which was inhibited in the RvD1 group. RvD1 could
inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which
was prohibited in RvD1 blockage group. RvD1 group also had a lower proportion of
apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group.
CONCLUSION: In LPS-induced AKI, RvD1 could decrease TNF-? level, ameliorate
kidney pathological injury, protect kidney function, and improve animal survival
by down-regulating NF-?B inflammatory signal as well as inhibiting renal cell
apoptosis.
|Acute Kidney Injury/chemically induced/*prevention & control
[MESH]
|Adaptor Proteins, Signal Transducing/analysis
[MESH]