Dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian decoction in a rat model of CCl4-induced liver fibrosis / 中华肝脏病杂志

ABSTRACT

To investigate the dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian (YGJ) Decoction on liver fibrosis induced by CCl4 in rat. Fifty-seven male Wistar rats were randomly divided into a liver fibrosis group (n = 39) and a normal group (n = 18). The liver fibrosis was treated with peritoneal injection of 50% CCl4 for nine weeks. At the end of weeks 3 and 6 of CCl4 treatment, six rats were sacrificed to assess the status of liver fibrosis. At the end of week 7, the remaining -fibrotic rats were randomly divided into an untreated model group (M, n=15) and a YGJ-treated group (n = 12). The YGJ group was administered daily, oral YGJ Decoction for three weeks, concomitant with continued CCl4 treatment. The M group and normal group received the same treatment oral regimen and volume of distilled water. At the end of week 8, four rats in group M were sacrificed to observed the fibrosis status. At the end of week 9, the fibrotic rats were sacrificed for sampling. Liver function, histological changes, contents of hydroxyproline (Hyp) and malondialdehyde (MDA), activity of super oxidase dismutase (SOD) and L-glutathione (GSH), protein expression of heat shock protein (HSP)70, heme oxygenase (HO)-1, transferrin, peroxiredoxin (Prxd) 6 and liver fatty acid binding protein (L-FABP) were detected. Compared with normal group-, the MDA content was increased significantly in M group at week 6 (M: 4.23+/-0.45 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 60.13, P less than 0.01) and week 9 (M: 6.29+/-1.23 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 66.99, P less than 0.01), but the SOD activity was decreased significantly at the same time points [week 6: (M: 196.94+/-39.20 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 11.12, P less than 0.01]); [week 9: (M: 152.2+/-51.65 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 23.11, P less than 0.01)], as were the GSH content [week 6: (M: 48.47+/-7.27 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 6.71, P less than 0.05]]; [week 9: (M: 37.89+/-9.01 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 24.06, P less than 0.01]]. Compared with group M at week 9, the YGH-treated model group had markedly decreased MDA (YGJ: 4.25+/-0.86 nmol/mg vs. M: 6.29+/-1.23 nmol/mg, F = 19.52, P less than 0.01], but significantly increased SOD (YGJ: 198.35+/-46.48 U/mg vs. 152.21+/-51.65 U/mg, F = 4.65, P less than 0.05] and GSH (YGJ: 53.73+/-7.54 nmol/mg vs. M: 37.89+/-9.01 nmol/mg, F = 19.23, P less than 0.01). Compared to normal rats at week 9, group M had significantly higher protein levels of HSP70 (normal: 1.21+/-0.06 vs. M: 0.58+/-0.07, F = 166.87, P less than 0.01) and HO-1 (normal: 1.11+/-0.06 vs. M: 0.58+/-0.06, F = 123.96, P less than 0.01), but significantly decreased levels of Prxd6 (normal: 0.04+/-0.05 vs. M: 1.49+/-0.05, F = 1215.85, P less than 0.01), transferrin (normal: 0.67+/-0.03 vs. M: 1.67+/-0.04, F = 301.35, P less than 0.01), and L-FABP (normal: 0.24+/-0.02 vs. M: 1.44+/-0.14, F = 219.05, P less than 0.01). Compared to group M at week 9, the YGJ treatment group showed significantly reduced HSP70 (YGJ: 0.82+/-0.04 vs. M: 1.21+/-0.06, F = 92.31, P less than 0.01) and HO-1 (YGJ: 0.90+/-0.04 vs. 1.11+/-0.06, F = 26.89, P less than 0.01), but significantly increased Prxd6 (YGJ: 0.88+/-0.11 vs. 0.04+/-0.05, F = 150.17, P less than 0.01), transferrin (YGJ: 1.36+/-0.13 vs. 0.24+/-0.02, F = 237.19, P less than 0.01), and L-FABP (YGJ: 1.04+/-0.12 vs. 0.67+/-0.03, F = 27.53, P less than 0.01). YGJ treatment of fibrotic liver rats reduces lipid peroxidation damage by preventing generation of oxidizing substances.