Abstract:

Objective To investigate the anti-inflammatory effect of aucubin on colitis in rats exposed to cadmium and its effect on p38MAPKNF-κB signaling pathway，provide reference for the prevention and treatment of intestinal diseases related to environmental heavy metal cadmium exposure. Methods Totally 40 rats were randomly divided into control group，cadmium exposure model group，and low- and high-dose aucubin groups based on their body weight，10 rats in each group，half male and half female. The control group was gavaged with an equal volume of normal saline，the cadmium exposure group was gavaged with 0.5 mg/kg CdCl₂ solution daily，and the low- and high-dose aucubin groups were gavaged with 25 and 50 mg/kg aucubin solution daily on the basis of cadmium exposure. After the experiment，the colonic mucosal damage index（CMDI），disease activity index（DAI），colon inflammation scores，and colon cell apoptosis rates of the rats in each group were measured. The real time fluorescence reverse transcription and Western blotting were used to test mRNA and protein expression level of mitogen-activated protein kinase p38（p38MAPK） and nuclear factor kappa-light-chain-enhancer of activated B cells（NF-κB） in colon tissue. The enzyme-linked immunosorbent assay was used to test levels of tumor necrosis factor-α（TNF-α），interleukin-6（IL-6） and monocyte chemoattractant protein-1（MCP-1） in colon tissue. Results Compared with the control group，the CMDI（12.25±1.12），DAI（2.71±0.23），colon inflammation score（7.24±1.22），apoptosis rate[（29.54±2.99）%]，p38MAPK mRNA（4.69±0.65），NF-κB mRNA（4.27±0.48），p38MAPK protein（1.06±0.10），NF-κB protein（1.12±0.13），TNF-α[（459.14±29.24）mmol/mL]，IL-6[（541.20±33.21）mmol/mL] and MCP-1[（625.36±42.27）mmol/mL] in the cadmium exposure model group were significantly increased（all P<0.05）. Compared with the cadmium exposure model group，the CMDI（8.54±0.85），DAI（1.81±0.18），colon inflammation score（5.30±0.54），apoptosis rate[（16.24±1.23）%]，p38MAPK mRNA（3.24±0.45），NF-κB mRNA（3.05±0.33），p38MAPK protein（0.75±0.07），NF-κB protein（0.80±0.08），TNF-α[（236.41±19.47）mmol/mL]，IL-6[（302.14±25.22）mmol/mL] and MCP-1[（337.48±32.17）mmol/mL] in low-dose aucubin group were significantly decreased（all P<0.05）. While CMDI（5.24±0.56），DAI（1.28±0.09），colon inflammation score（3.22±0.41），apoptosis rate[（3.22±0.47）%]，p38MAPK mRNA（2.33±0.23），NF-κB mRNA（1.25±0.19），p38MAPK protein（0.35±0.04），NF-κB protein（0.42±0.05），TNF-α[（130.20±15.11）mmol/mL]，IL-6[（184.20±19.11）mmol/mL]，MCP-1[（209.54±22.19）mmol/mL] in high-dose aucubin group were further decreased，and those were significantly decreased as compared with lower-dose aucubin group（all P<0.05）. Conclusion The aucubin exhibits a significant anti-inflammatory therapeutic effect on colitis in cadmium-exposed rats，its mechanism is related to the significant inhibition of the activation of the p38MAPK/NF-κB signaling pathway by aucubin.

Key words: Aucubin, Cadmium exposure, Colitis, Mitogen-activated protein kinase p38, Nuclear factor-κB