Research Article: LBP reduces theinflammatory injuryof kidney in septic rat and regulates the Keap1-Nrf2∕ARE signaling pathway1

Date Published: February 14, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Yayi Huang, Fang Zhou, Chen Shen, Huaxin Wang, Yeda Xiao.


To investigate the influence of lycium barbarum polysaccharides (LBP), a
functional derivative from lycium barbarum, on septic kidney injury.

The SD male rats were randomly divided into 8 groups. The concentration of
IL-1β, IL-6, IL-8, TNF-α, NF-κB and ROS, in kidney cortex homogenates after
12 h treatments were determined by enzyme-linked immunosorbent assay and ROS
test kit, respectively. Morphology observation of kidney tissue was
conducted with HE staining. The mRNA and protein expression levels of Nrf2,
HO-1, NQO1, NF-κB, and Keap1 in kidney tissues were determined by qRT-PCR
and Western blot, respectively.

LPS treatment significantly increased the oxidative stress. After LBP
treatment, the ROS content reduced significantly in a dose-depend manner.
However, the levels of HO-1, NQO1 and Nrf2 as molecular elements that
respond to oxidative stress were further increased. Also, administration of
LBP increased the levels of NF-κB and Keap1, and decreased the levels of
Nrf2 in the Keap 1-Nrf2∕ARE signaling pathway. By administrating the
brusatol, the inhibition of Nrf2 enhanced the expression of NF-κB, inhibits
the antioxidant responses, and further reverse the protective effect of LBP
on the LPS induced septic kidney injury.

Lycium barbarum polysaccharides can reduce inflammation and activate the
antioxidant responses via regulating the level of pro-inflammatory cytokines
and the Keap1-Nrf2/ARE signaling pathway.

Partial Text

Sepsis is a kind of systemic inflammatory response syndrome (SIRS), mainly infected
by bacteria, fungi, viruses and parasites1. The SIRS caused by sepsis may incur function damage of systemic multiple
organ, like septic acute kidney injury (AKI)2. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is an important
transcription factor in oxidative stress response. It regulates antioxidant response
elements (AREs)-mediate depression of antioxidant enzyme and cytoprotective
proteins. Moreover, multiple studies have demonstrated that Nrf2-Keap1 (Kelch-like
ECH-associated protein 1)-ARE signal pathway involves in the endogenous antioxidant
defense mechanisms and it is an important signaling pathway in oxidative stress

Inflammatory injury and oxidative-stress are important factors of the pathogenesis
of sepsis and tissue damage12,13. Our study found that the concentration of IL-1β, IL-6, IL-8, TNF-α and
NF-κB in rat kidney tissues increased significantly at 12h after injection with LPS,
however, after different doses of LBP injection, the concentration of these
inflammatory cytokines presented a significant reduction. These findings suggest
that LBP treatment can play a protective role on the inflammation damage of septic
rat kidney.

Taken together, our results suggest that LBP can up-regulate the level of Nrf2 and
down-regulate the pro-inflammatory cytokines, and further regulating the
Keap1-Nrf2/ARE signaling pathway, consequently activating the antioxidant responses
and reducing inflammation. Along with in-depth research of sepsis and inflammatory
injury, the mechanism by which how to reduce the oxidative stress in sepsis damage
to the body is still not very clear. Therefore, further studies and development are
still needed, which could provide a better foundation for clinical treatment of
septic kidney injury.




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