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Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway

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Abstract

Objective

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

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

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

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.

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Authors and Affiliations

  1. Nephropathy Department, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518034, China

    Ruo-lin Wang, Si-heng Shen, Lu-yong Jian, Qi Yuan, Hua-hui Guo, Jia-sheng Huang, Peng-hui Chen & Ren-fa Huang

  2. The Third Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Ruo-lin Wang, Shu-hua Liu, Si-heng Shen, Lu-yong Jian & Qi Yuan

Authors
  1. Ruo-lin Wang
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  2. Shu-hua Liu
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  6. Hua-hui Guo
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  9. Ren-fa Huang
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Contributions

Wang RL designed the experimental scheme, conceived and wrote the manuscript. Shen SH collected materials and participated in the experimental process. Jian LY made the first revision of the manuscript. Liu SH contributed to manuscript drafting. Guo HH submitted the final manuscript. Yuan Q, Huang JS and Chen PH participated in the experimental process. Huang RF put forward theoretical ideas and modified the final manuscript. All authors participated in this article and finally approved the submitted and published version.

Corresponding author

Correspondence to Ren-fa Huang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81460682), the Natural Science Foundation of Guangdong Province (No. 2020A1515010566), and the Shenzhen Foundation of Science and Technology Research and Development (No. JCYJ20190809102413156)

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Wang, Rl., Liu, Sh., Shen, Sh. et al. Protective Mechanism of Cordyceps sinensis Treatment on Acute Kidney Injury-Induced Acute Lung Injury through AMPK/mTOR Signaling Pathway. Chin. J. Integr. Med. 29, 875–884 (2023). https://doi.org/10.1007/s11655-023-3593-4

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