桃叶珊瑚苷对镉暴露大鼠结肠炎的抗炎作用及p38MAPKNF-κB信号通路的影响

摘要/Abstract

摘要：

目的了解桃叶珊瑚苷对镉暴露大鼠结肠炎的抗炎作用及p38MAPKNF-κB信号通路的影响，为环境重金属镉暴露相关肠道疾病的防治提供参考依据。方法 40只大鼠按照体质量随机分为对照组、镉暴露模型组、桃叶珊瑚苷低、高剂量组，每组10只，雌雄各半；对照组予以等体积生理盐水灌胃，镉暴露组每日灌胃0.5 mg/kg CdCl₂溶液，桃叶珊瑚苷低、高剂量组在镉暴露基础上，每日灌胃25、50 mg/kg桃叶珊瑚苷溶液。实验结束后，测定各组大鼠结肠黏膜损伤指数（colonic mucosal damage index，CMDI）、疾病活动指数（disease activity index，DAI）、结肠炎症评分、结肠细胞凋亡率水平，实时荧光逆转录法及蛋白印迹法测定结肠组织丝裂原活化蛋白激酶p38（mitogen-activated protein kinase p38，p38MAPK）、核因子-κB（nuclear factor kappa-light-chain-enhancer of activated B cells，NF-κB）mRNA和蛋白表达水平，酶联免疫吸附法测定结肠组织肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、单核細胞趋化蛋白-1（monocyte chemoattractant protein-1，MCP-1）水平。结果与对照组相比，镉暴露模型组CMDI（12.25±1.12）、DAI（2.71±0.23）、结肠炎症评分（7.24±1.22）、凋亡率[（29.54±2.99）%]、p38MAPK mRNA（4.69±0.65）、NF-κB mRNA（4.27±0.48）、p38MAPK蛋白（1.06±0.10）、NF-κB蛋白（1.12±0.13）、TNF-α[（459.14±29.24）mmol/mL]、IL-6[（541.20±33.21）mmol/mL]、MCP-1[（625.36±42.27）mmol/mL]均显著升高，差异均有统计学意义（均P<0.05）。与镉暴露模型组相比，桃叶珊瑚苷低剂量组CMDI（8.54±0.85）、DAI（1.81±0.18）、结肠炎症评分（5.30±0.54）、凋亡率[（16.24±1.23）%]、p38MAPK mRNA（3.24±0.45）、NF-κB mRNA（3.05±0.33）、p38MAPK蛋白（0.75±0.07）、NF-κB蛋白（0.80±0.08）、TNF-α[（236.41±19.47）mmol/mL]、IL-6[（302.14±25.22）mmol/mL]、MCP-1[（337.48±32.17）mmol/mL]均显著降低，差异均有统计学意义（均P<0.05）；高剂量组CMDI（5.24±0.56）、DAI（1.28±0.09）、结肠炎症评分（3.22±0.41）、凋亡率[（3.22±0.47）%]、p38MAPK mRNA（2.33±0.23）、NF-κB mRNA（1.25±0.19）、p38MAPK蛋白（0.35±0.04）、NF-κB蛋白（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]进一步降低，且较桃叶珊瑚苷低剂量组均显著降低，差异均有统计学意义（均P<0.05）。结论桃叶珊瑚苷对镉暴露大鼠结肠炎表现出明显的抗炎治疗作用，其机制与桃叶珊瑚苷明显抑制p38MAPK/NF-κB信号通路的激活有关。

关键词: 桃叶珊瑚苷, 镉暴露, 结肠炎, 丝裂原活化蛋白激酶p38, 核因子-κB

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

中图分类号:

R-332

姚小波, 刘飞, 肖方怡, 冯亮. 桃叶珊瑚苷对镉暴露大鼠结肠炎的抗炎作用及p38MAPKNF-κB信号通路的影响. [J]职业与健康, 2026, 42(9): 1179-1185.

YAO Xiaobo, LIU Fei, XIAO Fangyi, FENG Liang. Anti-inflammatory effect of aucubin on colitis in cadmium-exposed rats and its influence on p38MAPKNF-κB signaling pathway. [J]OCCUPATION AND HEALTH, 2026, 42(9): 1179-1185.

图/表 7

参考文献 20

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组别	只数	CMDI	DAI	结肠炎症评分
桃叶珊瑚苷高剂量组	10	5.24±0.56^ab	1.28±0.09^ab	3.22±0.41^ab
桃叶珊瑚苷低剂量组	10	8.54±0.85^a	1.81±0.18^a	5.30±0.54^a
镉暴露模型组	10	12.25±1.12^c	2.71±0.23^c	7.24±1.22^c
对照组	10	0.00±0.00	0.00±0.00	0.00±0.00
F值		16.354	15.659	19.854
P		<0.01	<0.01	<0.01

组别	只数	CMDI	DAI	结肠炎症评分
桃叶珊瑚苷高剂量组	10	5.24±0.56^ab	1.28±0.09^ab	3.22±0.41^ab
桃叶珊瑚苷低剂量组	10	8.54±0.85^a	1.81±0.18^a	5.30±0.54^a
镉暴露模型组	10	12.25±1.12^c	2.71±0.23^c	7.24±1.22^c
对照组	10	0.00±0.00	0.00±0.00	0.00±0.00
F值		16.354	15.659	19.854
P		<0.01	<0.01	<0.01

组别	只数	结肠细胞凋亡率（%）
桃叶珊瑚苷高剂量组	10	3.22±0.47^ab
桃叶珊瑚苷低剂量组	10	16.24±1.23^a
镉暴露模型组	10	29.54±2.99^c
对照组	10	0.63±0.15
F值		36.254
P		<0.01

组别	只数	结肠细胞凋亡率（%）
桃叶珊瑚苷高剂量组	10	3.22±0.47^ab
桃叶珊瑚苷低剂量组	10	16.24±1.23^a
镉暴露模型组	10	29.54±2.99^c
对照组	10	0.63±0.15
F值		36.254
P		<0.01

组别	只数	p38MAPK mRNA	NF-κB mRNA	p38MAPK蛋白（/β-actin）	NF-κB蛋白（/β-actin）
桃叶珊瑚苷高剂量组	10	2.33±0.23^ab	1.25±0.19^ab	0.35±0.04^ab	0.42±0.05^ab
桃叶珊瑚苷低剂量组	10	3.24±0.45^a	3.05±0.33^a	0.75±0.07^a	0.80±0.08^a
镉暴露模型组	10	4.69±0.65^c	4.27±0.48^c	1.06±0.10^c	1.12±0.13^c
对照组	10	0.45±0.15	0.69±0.23	0.19±0.03	0.22±0.02
F值		19.549	26.526	16.336	18.512
P		<0.01	<0.01	<0.01	<0.01