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Volume 40 Issue 11
Nov.  2024
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Article Navigation >  Journal of Clinical Hepatology  > 2024  >  40(11): 2213-2220

Effect of Xiayuxue Decoction against renal injury in mice with non-alcoholic fatty liver disease and its mechanism

DOI: 10.12449/JCH241114
  • a.

    Central Laboratory，Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200062，China

  • b.

    Laboratory of Liver Diseases，Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200062，China）

  • c.

    Department of Infectious Diseases，Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，Shanghai 200062，China

Research funding:

National Natural Science Foundation of China (82004106);

Shanghai National Natural Science Foundation (20ZR1450300);

Indenpent Innovation of Shanghai Putou District Project (ptkwws202223);

Shanghai Traditional Chinese Medicine High level Talent Leading Plan (ZY［2021-2023］-0403);

Putuo Xinglin Excellent Youth Training Program (ptxlyq2301)

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  • Corresponding author: LIU Xuling， lxlqiqi@163.com （ORCID： 0000-0003-3994-8475）; LIU Cheng， liucheng0082010@163.com （ORCID： 0000-0002-8741-6169）
  • Received Date: 2024-02-21
  • Accepted Date: 2024-05-20
  • Published Date: 2024-11-25
    Abstract
  •   Objective  To investigate the effect of non-alcoholic fatty liver disease （NAFLD） induced by high-fat diet （HFD） on the kidneys of mice and the protective effect and mechanism of Xiayuxue Decoction.  Methods  A total of 25 healthy controls and 25 NAFLD patients who attended Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from September 2020 to September 2021 were enrolled， and the levels of total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， creatinine （Cr）， and uric acid （UA） were measured. A total of 24 male C57BL/6 mice were randomly divided into low-fat diet （LFD） group， HFD group， and HFD+Xiayuxue Decoction group （XYXD group）， with 8 mice in each group， and since week 13， XYXD was administered by gavage once a day for 6 weeks till the end of week 18. The level of TC， TG， BUN， and Cr were measured for each group. HE staining and oil red staining were used to observe the pathological changes of the liver and the kidneys； immunohistochemical double staining was used to measure the expression levels of CD68 and alpha-smooth muscle actin （α-SMA）； quantitative real-time PCR was used to measure the expression levels of sterol regulatory element binding protein 1 （SREBP1）， fatty acid synthase （FASN）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， Desmin， and α-SMA in renal tissue； Western blot was used to measure the protein expression levels of SREBP1 and TNF-α. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for pairwise comparison； the independent-samples t-test was used for comparison between two groups.  Results  Compared with the healthy controls， NAFLD patients showed significant increases in the levels of TC， TG， BUN， Cr， and UA （all P<0.05）. Compared with the LFD group， the HFD group had significant increases in body weight， TC， TG， BUN， and Cr （all P<0.001）， and compared with the HFD group， the XYXD group showed significant inhibition of the expression of TC， TG， BUN， and Cr （all P<0.001）. Liver pathological examination showed that compared with the LFD group， the HFD group showed significant increases in hepatic steatosis and inflammatory infiltration， while the XYXD group showed significant alleviation of lesions. Renal pathological examination showed that compared with the LFD group， the HFD group had significant inflammatory infiltration， steatosis， and collagen formation in renal tissue， and compared with the HFD group， XYXD significantly alleviated inflammatory infiltration and inhibited steatosis and collagen formation. Quantitative real-time PCR showed that compared with the LFD group， the HFD group had significant increases in the relative mRNA expression levels of SREBP1， FASN， IL-6， TNF-α， Desmin， and α-SMA in renal tissue （all P<0.001）， and compared with the HFD group， the XYXD group had significant reductions in the relative expression levels of these indicators （all P<0.001）. Western blot showed that compared with the LFD group， the HFD group had significant increases in the protein expression levels of SREBP1 and TNF-α （P<0.05）， and compared with the HFD group， the XYXD group had significant reductions in the protein expression levels of SREBP1 and TNF-α （P<0.05）. Immunohistochemical staining showed that compared with the LFD group， the HFD group had significant increases in the positive staining or the double positive staining of α- SMA and CD68 （P<0.05）， and compared with the HFD group， the XYXD group showed significant reductions （P<0.05）.  Conclusion  HFD can induce renal steatosis， inflammatory infiltration， and collagen formation， and XYXD might exert a protective effect on the kidneys by inhibiting the expression of macrophages and myofibroblasts in renal tissue.

     

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