Protection of curcumin to intestinal mucosal barrier by inhibiting enterocyte apoptosis in septic rats / 中华危重病急救医学

ABSTRACT

Objective:To study the effect of curcumin on enterocyte apoptosis and its protective effect on intestinal mucosal barrier in septic rats.Methods:Eighty-seven 3-month male Sprague-Dawley (SD) rats were divided into Sham group, model group and curcumin group by random number table method, with 29 rats in each group. The septic rat model was reproduced by cecal ligation and puncture (CLP). 4 mL dimethyl sulfoxide solution were intraperitoneally injected in both Sham group and model group, 200 mg/kg curcumin dissolved by 4 mL dimethyl sulfoxide solution were intraperitoneally injected in curcumin group 10 minutes after operation. The blood samples (15 rats in each group) were collected 2, 12, 24 hours after operation, and the levels of serum procalcitonin (PCT), tumor necrosis factor-α(TNF-α), D-lactic acid and diamine oxidas (DAO) were tested by enzyme linked immunosorbent assay (ELISA). The ileum tissues were collected 12 hours, 24 hours after operation in three groups, water content was tested by weighting, pathologic structure was observed by light microscope, the enterocyte apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling method (TUNEL). The 7-day survival rate was observed in three groups (14 rats in each group).Results:The serum levels of PCT, TNF-α, D-lactic acid and DAO were higher in model group at 2, 12, 24 hours after operation than those in Sham group, PCT, TNF-α levels were significantly higher in model group than those in Sham group 2 hours after operation [PCT (μg/L) 1.89±0.17 vs. 0.10±0.02, TNF-α (ng/L) 216.51±1.47 vs. 85.25±8.20, both P < 0.01], D-lactic acid, DAO levels were significantly higher in model group than those in Sham group 12 hours after operation [D-lactic acid (mg/L) 40.53±7.76 vs. 11.29±1.28, DAO (ng/L) 1 120.40±302.35 vs. 330.02±81.28, both P < 0.01]. Compared with model group, the levels of serum PCT, TNF-α, D-lactic acid and DAO were lower in curcumin group 2, 12, 24 hours after operation, the statistical difference appeared from 12 hours after operation [PCT (μg/L) 5.37±0.44 vs. 8.67±0.64, TNF-α(ng/L) 211.12±4.31 vs. 313.30±18.46, D-lactic acid (mg/L) 29.74±1.41 vs. 40.53±7.76, DAO (ng/L) 810.71±201.41 vs. 1 120.40±302.35, all P < 0.05], curcumin group had lower water content in ileum tissues 12 hours, 24 hours after operation [(68.34±0.68)% vs. (70.55±0.87)%, (69.41±0.59)% vs. (71.69±0.87)%, both P < 0.05]. The pathologic structures of intestinal villus were normal in Sham group, however, in model group intestinal villus were atrophic, edematous and shorten 12 hours after operation, it was further exacerbated 24 hours after operation. Compared with model group, the pathologic structures of intestinal villus in curcumin group were relived 12 hours, 24 hours after operation. The number of apoptotic enterocytes were significantly increased in model group compared with Sham group 24 hours after operation (cells 25.48±6.10 vs. 4.00±2.04, P < 0.05), and the number of apoptotic enterocytes was lower in curcumin group than that in model group at the same time (cells 15.48±3.75 vs. 25.48±6.10), the difference was statistically significant (both P < 0.05). Seven-day survival rate was significantly lower in curcumin than that in model group [42.9% (6/14) vs. 50.0% (7/14)], however, the difference was not statistically significant ( P > 0.05). Conclusion:Curcumin can protect the intestinal mucosal barrier by inhibiting enterocyte apoptosis in septic rats.