To investigate the role of chronic inflammatory injury in the occurrence of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in rats.

Forty healthy male Wistar rats were randomly divided into the DEN group (n=32) and control group (n=8) according to the random number table method. DEN (60 mg/kg) was administered in the DEN group via intraperitoneal injection once weekly for consecutive 8 weeks, and no drug was administered in the control group. In the DEN group, the liver tissues were obtained from 8 rats randomly for pathological examination at 4, 8, 12 and 16 week, and the portal venous blood was preserved. All rats were executed at 16 week. The inflammatory injury of liver tissues was observed by HE staining. The expression level of DNA repair protein γH2AX was detected by immunohistochemical staining. The expression levels of IL-6, VEGF and TNF-α were detected by ELISA. Serum inflammatory factors were compared among three groups using one-way analysis of variance and LSD-t test. The positive rate of γH2AX was compared between two groups using one-sample t test or independent-sample t test.

In the DEN group, the inflammatory injury of liver tissues was gradually aggravated at 4, 8, 12 and 16 week, and eventually progressed into HCC. No pathological abnormality was observed in the control group. The positive rate of γH2AX in the liver tissues at 4, 8, 12 and 16 week was respectively (0.3±0.1)%, (3.1±0.6)%, (7.8±2.8)% and (11.4±2.3)% in the DEN group, significantly higher than 0 in the control group (Z=2.34, 2.84, 4.11, 5.31; P<0.05). The level of serum IL-6 at 4, 8, 12 and 16 week was respectively (104±7), (117±10), (168±16) and (181±11) ng/L in the DEN group, significantly higher than (83±53) ng/L in the control group (LSD-t= 5.19, 8.41, 21.03, 24.25; P<0.05). The level of serum VEGF at 4, 8, 12 and 16 week was respectively (257±16), (302±21), (387±36) and (439±26) ng/L in the DEN group, significantly higher than (164±15) ng/L in the control group (LSD-t=10.17, 15.04, 24.39, 29.18; P<0.05). The level of serum TNF-α at 4, 8, 12 and 16 week was respectively (108±5), (125±11), (156±17) and (181±14) ng/L in the DEN group, significantly higher than (79±6) ng/L in the control group (LSD-t= 7.30, 11.59, 19.39, 25.70; P<0.05).

Chronic inflammatory injury of the liver plays a pivotal role in the occurrence of HCC induced by DEN in rats, and the course is accompanied with high levels of inflammatory cytokines and persistent DNA injury.