Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (13): 2049-2054.doi: 10.3969/j.issn.2095-4344.1644

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Combination of resveratrol and fetal liver stem cell transplantation for treatment of liver cirrhosis in rats

Wang Yuxuan   

  1. Department of Hepatobiliary and Gastrointestinal Surgery, Tianjin 4th Center Hospital, Tianjin 300140, China
  • Revised:2018-12-15 Online:2019-05-08 Published:2019-05-08
  • About author:Wang Yuxuan, Attending physician, Department of Hepatobiliary and Gastrointestinal Surgery, Tianjin 4th Center Hospital, Tianjin 300140, China

Abstract:

BACKGROUND: Low-dose resveratrol can promote cell activation and show synergy with fetal liver stem cell transplantation for liver cirrhosis in rats.
OBJECTIVE: To observe and investigate the effects of resveratrol and fetal liver stem cell transplantation on the rat with liver cirrhosis. 
METHODS: Eighty-four Sprague-Dawley adult rats were intragastrically administered with carbon tetrachloride to induce liver cirrhosis, and the animal model of liver cirrhosis was successfully made in 81 rats. After the successful modeling, 80 of the 81 model rats were randomly divided into four groups (n=20/group): the rats in the control group were injected with 0.5 mL of low-dose Dulbecco’s modified Eagle’s medium into the tail vein; the rats in the fetal liver stem cell group were injected with 0.5 mL of fetal liver stem cell suspensions into the tail vein; the rats in the resveratrol group was intragastrically administered with 120 mg/kg resveratrol; and the rats in the combination group were given injection of fetal liver stem cell suspension and administration of resveratrol. All treatments were given once daily for 7 consecutive days. After 3 weeks of treatment, the indocyanine green excretion test was used to determine the 15-minute retention rate of indocyanine green. The biochemical indicators of the serum and liver tissues were detected by an automatic biochemical analyzer. Morphological changes of the liver tissue were observed by hematoxylin-eosin staining. Transforming growth factor β1 gene and protein expression in the liver tissue was detected by RT-PCR and western blot, respectively.
RESULTS AND CONCLUSION: (1) Compared with the control group, the levels of serum alanine aminotransferase, serum aspartate aminotransferase, serum total bilirubin and malondialdehyde in the liver tissue were significantly reduced in the fetal liver stem cell group and resveratrol group (P < 0.01), while serum albumin level, total protein level, albumin/globulin, and glutathione peroxidase level and cyclic guanosine monophosphate level in the liver tissue were significantly increased in these two groups (P < 0.05). These aforementioned biochemical indicators in the combination group were significantly improved as compared with the fetal liver stem cells group and resveratrol group (P < 0.05). (2) Hepatocyte degeneration, necrosis and fibrosis were significantly reduced in the three treatment groups, especially in the combination group. (3) Compared with the control group, the 15-minute retention rate of indocyanine green was significantly increased after resveratrol intervention and fetal liver stem cell transplantation (P < 0.05), and further increased after combination treatment (P < 0.01). (4) Compared with the control group, the expression of transforming growth factor β1 was significantly decreased in the resveratrol group and fetal liver stem cell group (P < 0.05), and further decreased in the combination group (P < 0.01). To conclude, resveratrol treatment combined with fetal liver stem cell transplantation can effectively improve the levels of blood biochemical markers and significantly reduce the degree of liver cirrhosis and hepatic histopathological changes in the rats with liver cirrhosis. This may be related to the decreased expression of transforming growth factor β1 gene and protein.

Key words: Liver Cirrhosis, Liver, Stem Cell Transplantation, Transforming Growth Factor beta1, Tissue Engineering

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