Published online May 15, 2003. doi: 10.3748/wjg.v9.i5.1028
Revised: November 23, 2002
Accepted: December 30, 2002
Published online: May 15, 2003
AIM: To investigate the regulatory effect of electroacupuncture (EA) at Zusanli (ST36) on tumor necrosis factor-alpha (TNF-α) in rats with ulcerative colitis (UC), and further elucidate the therapeutic mechanism of EA on UC.
METHODS: Thirty-two male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 8): normal control group, UC control group, UC+ST36 group and UC+non-acupoint group. A solution containing ethanol and 2,4,6-trinitrobenzenesulfonic acid (TNBS) was instilled into the distal colon in the rat (at a dose of 100 mg/kg) to set up UC rat model. Rats in wakefulness state of UC+ST36 group were stimulated at ST36 by EA once a day, while those of UC+non-acupoint group were done at 0.5 cm beside ST36. After 10 d treatment, all rats were sacrificed simultaneously. Colon musocal inflammation and damage were assessed by measuring colon mass, morphologic damage score, colonic myeloperoxidase enzyme (MPO) activity, serum TNF-α and colonic TNF-α mRNA level. Morphologic damage score was examined under stereomicroscope. Colonic MPO activity was measured by spectrophotometer method. Serum TNF-α concentration was determined by radioimmunoassay (RIA). Colonic TNF-α mRNA expression level was analyzed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR).
RESULTS: Ratio of colonic mass/body mass (mC/mB) and activity of colonic MPO (μkat/g tissue) markedly increased (8.5 ± 2.6 vs 2.5 ± 0.4; 145 ± 25 vs 24 ± 8, P < 0.01 vs normal control group). Compared with normal control rats, serum TNF-α and colonic TNF-α mRNA level in UC control group were increased 2.5 fold (2278 ± 170 vs 894 ± 248, P < 0.01) and 4.3 fold (0.98 ± 0.11 vs 0.23 ± 0.11, P < 0.01) respectively. After EA at ST36, mC/mB and MPO activity were reduced significantly (5.3 ± 2.0 vs 8.5 ± 2.6; 104 ± 36 vs 145 ± 25, P < 0.01, 0.05) compared with those of UC control group. Serum TNF-α and colonic TNF-α mRNA level were inhibited by EA stimulation at ST36 (P < 0.01). The inhibitory rate was 16% and 44% respectively. Morphologic damage score was also increased markedly in rat with UC (P < 0.01), whereas it was decreased by EA at ST36 (P < 0.05). There was no significant difference between UC control group and UC+EA at non-acupoint (P > 0.05). Furthermore, these parameters were highly correlated with each other (P < 0.01).
CONCLUSION: Serum TNF-α concentration and colonic TNF-α mRNA expression level are increased significantly in UC rats in correlation with the severity of disease. It indicates that TNF-α is closely involved in the immune abnormalities and inflammatory responses in UC. EA at ST36 has therapeutic effect on UC by downregulating serum TNF-α and colonic TNF-α mRNA expression. High levels of TNF-α and its corresponding mRNA expression seem to be implicated in the pathogenesis of UC.