Objective:

2

To investigate the protective effects and potential mechanisms of Shenhua Tablet (肾华片

SHT) on the toll-like receptors (TLRs)-mediated signaling pathways in a rat model of kidney ischemia-reperfusion injury (IRI).

Methods:

2

Sixty male Wistar rats were randomly divided into 5 groups: sham surgery

model control

astragaloside (150 mg•kg

-1

•d

-1

)

low- and high-dose SHT (1.5 and 3.0 g•kg

-1

•d

-1

repectively) groups. One week after drug treatment

rats underwent surgery to establish the IRI models. At 24 h and 72 h after the modeling

serum creatinine (Scr) and blood urea nitrogen (BUN) were analyzed; pathological damage were scored after periodic acid-Schiff staining. TLR2

TLR4 and myeloid differentiation factor 88 (MyD88) protein and mRNA expressions were detected by inmmunohistochemistry

Western blot and qPCR. Tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) protein expressions were detected by enzyme linked immunosorbent assay.

Results:

2

Compared with the sham group

the model group exhibited severe change in renal function (Scr: 189.42±21.50

P

<

0.05)

pathological damage (damage score: 4.50±0.55

P

<

0.05)

and the expression levels of TLR2

TLR4

MyD88

TNF-α

IL-6 were significantly higher than other groups. Meanwhile

the levels of TLRs in model group showed upward tendency from 24 to 72 h

unparalleled with pathological and functional changes. The aforementioned parameters were alleviated to a certain extent

and

in addition to TLRs

presented the obvious downward trending from the 24 to 72 h after the intervention in the SHT and astragaloside groups relative to the model (

P

<

0.05); in particular

the most significant mitigation of these changes was observed in the SHT-H group (

P

<

0.05).

Conclusions:

2

TLRs may be an important spot to treat and research in acute kidney injury. SHT could effectively mitigate renal injuries and promote recovery of IRI injuries through suppression of degeneration induced by up-regulation of TLR2 and TLR4 expression levels in the MyD88-dependent signaling pathway and exhibit some dose dependence.