Objective:

2

To investigate protective effect of

Cordyceps sinensis

(CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI).

Methods:

2

Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table

including the normal saline (NS)-treated sham group (sham group)

NS-treated ischemia reperfusion injury (IRI) group (IRI group)

and low- (5 g/kg•d) and high-dose (10 g/kg•d) CS-treated IRI groups (CS1 and CS2 groups)

12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12

24

48

and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung

levels of serum creatinine (Scr)

blood urea nitrogen (BUN)

inflammatory cytokines such as interleukin-β and tumor necrosis factor-α

and biomarkers of oxidative stress such as superoxide dismutase

malonaldehyde (MDA) and myeloperoxidase (MPO)

were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 Ⅱ/light chain 3 Ⅰ (LC3-Ⅱ/LC3-Ⅰ)

uncoordinated-51-like kinase 1 (ULK1)

P62

AMPK and mTOR were measured by Western blot and immunohistochemistry

respectively.

Results:

2

The renal IRI induced pulmonary injury following AKI

resulting in significant increases in W/D ratio of lung

and the levels of Scr

BUN

inflammatory cytokines

MDA and MPO (

P

<

0.01); all of these were reduced in the CS groups (

P

<

0.05 or

P

<

0.01). Compared with the IRI groups

the expression levels of P62 and mTOR were significantly lower (

P

<

0.05 or

P

<

0.01)

while those of LC3-Ⅱ/LC3-Ⅰ

ULK1

and AMPK were significantly higher in the CS2 group (

P

<

0.05 or

P

<

0.01).

Conclusion:

2

CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI.