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Role of Autophagy in Liver Fibrosis with Qi Deficiency and Blood Stasis Via the Nrf2-Keap1-Are Signaling Pathway

  • Yuan Ouyang1,
  • Ke-Yang Xu1,
  • Xiao-Qian Shu1 and
  • Jian-Feng Bao2,*
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Abstract

Background and Aims

To investigate the mechanism underlying the role of the Nrf2-Keap1-Are oxidative stress pathway in liver fibrosis related to qi deficiency and blood stasis.

Methods

A total of 30 Sprague–Dawley rats were randomly divided into a normal group, a qi deficiency and blood stasis group, and a Fuzheng Huayu treatment group. After death, body weights and liver wet weights were measured and liver sections were stained with Sirius red. RT-PCR was used to detect the mRNA expression levels of α-SMA, Nrf2, Keap1, and β-actin, and western blotting was used to detect the protein expression levels of α-SMA, LC3II, P62, and LC3II.

Results

The Ishak score for liver fibrosis in the qi deficiency and blood stasis group was higher than that in the liver fibrosis group (P < 0.05) and decreased significantly following Fuzheng Huayu therapy (P < 0.05). As determined by PCR, α-SMA mRNA levels were highest in the qi deficiency and blood stasis group and were significantly higher than those in the treatment group (P < 0.05). Nrf2 and Keap1 mRNA expression levels were lowest in the qi deficiency and blood stasis group but increased significantly after treatment (P < 0.05). Western blotting showed that α-SMA and LC3II levels were highest in the qi deficiency and blood stasis group (P < 0.05) and decreased significantly after treatment (P < 0.05). The expression levels of P62, Nrf2, and Nqo1 were lowest in the qi deficiency and blood stasis group and increased significantly after treatment (P < 0.05).

Conclusions

LC3II can down-regulate the expression of P62 in liver tissues of rats with qi deficiency and blood stasis, thereby inhibiting the activation of the Nrf2-Keap1-Are antioxidant stress pathway and aggravating liver fibrosis. However, this process can be reversed by strengthening qi and activating blood circulation to alleviate blood stasis.

Keywords

Yiqi Huayu therapy, Qi deficiency and blood stasis, Liver fibrosis, Autophagy, LC3II, Nrf2- Keap1-Are signaling pathway

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Cite this article
Ouyang Y, Xu KY, Shu XQ, Bao JF. Role of Autophagy in Liver Fibrosis with Qi Deficiency and Blood Stasis Via the Nrf2-Keap1-Are Signaling Pathway. Gastroenterol & Hepatol Res. 2019;1(1):18-24. doi: 10.53388/ghr2019-12-005.
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Article History
Received Revised Accepted Published
December 12, 2019
DOI http://dx.doi.org/10.53388/ghr2019-12-005
  • Gastroenterology & Hepatology Research
  • eISSN 2703-173X
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Role of Autophagy in Liver Fibrosis with Qi Deficiency and Blood Stasis Via the Nrf2-Keap1-Are Signaling Pathway

Yuan Ouyang, Ke-Yang Xu, Xiao-Qian Shu, Jian-Feng Bao
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