Objective To study the protective effect and mechanism of Paeonia lactiflora polysaccharides on liver fibrosis with liver yin deficiency syndrome in rats based on mitochondrial dynamics. Methods Male SD rats were randomly divided into control group, model group, silybin (42 mg/kg) group, Zhibai Dihuang Wan (知柏地黄丸, 408 mg/kg) group and P. lactiflora polysaccharide low-, high-dose (169, 338 mg/kg) groups, with eight rats in each group. Drugs were continuously intervented for six weeks, starting from the second week of administration, except for the control group, all other rats were treated with an ip 20% carbon tetrachloride olive oil solution combined with ig thyroid tablets (30 mg/kg) to establish a liver fibrosis with liver yin deficiency syndrome model. Sign score, body weight, food intake, water intake, tongue surface moisture level and rectal temperature of rats were detected. Levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in serum were measured using ELISA, and ratio was calculated. Activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP) and levels of total bilirubin (TBIL), total bile acids (TBA) in serum were measured using colorimetric assays. Hematoxylin-eosin (HE) and Masson staining were used to observe the pathological changes and degree of liver fibrosis. Transmission electron microscopy was used to observe mitochondrial ultrastructure in liver. Immunofluorescence was used to detect reactive oxygen species (ROS) level in liver. Adenosine triphosphate (ATP) level was measured to using a kit. Western blotting was used to detect fibronectin 1 (FN1), collagen I (COL-I), α-smooth muscle actin (α-SMA), extracellular regulated protein kinases (ERK), p-ERK, p38, p-p38, fission 1 (Fis1), dynamin-related protein 1 (Drp1), p- Drp1, optic atrophy 1 (Opa1) and mitofusin 2 (Mfn2) protein expression levels in liver of rats. Results Compared with model group, the body weight, fecal consistency score and tongue surface moisture of rats in P. lactiflora polysaccharides group were significantly increased (P < 0.05, 0.01, 0.001), while mental state, coat luster, urine score, overall physical condition score, rectal temperature, food and water intake were significantly decreased (P < 0.05, 0.01, 0.001), cAMP level was decreased and cGMP level in serum was increased (P < 0.001), and cAMP/cGMP value was significantly reduced (P < 0.001), liver function related indicators were significantly reduced (P < 0.05, 0.01, 0.001), liver tissue pathological damage was improved, the collagen fiber area was significantly reduced (P < 0.001), and the expression levels of liver fibrosis proteins α-SMA, COL-I and FN1 were significantly decreased (P < 0.01, 0.001), the morphology and structure of mitochondria in liver were improved, ROS level in liver was decreased and ATP level was increased (P < 0.05, 0.01, 0.001), expression levels of p-ERK/ERK, p-p38/p38, Fis1 and p-Drp1/Drp1 proteins were significantly reduced (P < 0.05, 0.01, 0.001), while the expression levels of Opa1 and Mfn2 proteins were significantly increased (P < 0.01, 0.001). Conclusion P. lactiflora polysaccharides have a protective effect on liver fibrosis in rats with liver yin deficiency syndrome, and its mechanism may be related to the inhibition of ERK/p38 MAPK pathway to regulate mitochondrial dynamic homeostasis.

Paeonia lactiflora polysaccharides  /  liver fibrosis  /  liver yin deficiency syndrome  /  mitochondrial dynamics  /  ERK/p38 MAPK pathway