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中药灌肠液辅助治疗溃疡性结肠炎的作用机制研究

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目的 基于分子药理学方法研究一种中药灌肠制剂对小鼠溃疡性结肠炎的保护及辅助治疗作用。方法 构建葡聚糖硫酸钠盐诱导的溃疡性结肠炎小鼠模型,随机分为正常对照组、模型对照组、美沙拉嗪组、美沙拉嗪+灌肠液组,除正常对照组外,其余各组小鼠每天自由饮用4%葡聚糖硫酸钠盐溶液7 d。美沙拉嗪+灌肠液组每天灌胃给予0。52 g·kg-1 美沙拉嗪,且每天早晚用自制中药制剂灌肠;美沙拉嗪组每天灌胃给予0。52 g·kg-1 美沙拉嗪,且每天早晚用0。9%氯化钠溶液灌肠;正常对照组和模型对照组每天用0。9%氯化钠溶液灌胃,且每天早晚用0。9%氯化钠溶液灌肠,连续14 d后,取结肠组织冷冻备用。结果 溃疡性结肠炎可使小鼠体质量显著下降,美沙拉嗪可以帮助小鼠减少体质量下降趋势,美沙拉嗪+灌肠液组效果优于美沙拉嗪组。苏木精-伊红染色法染色及组织学评分结果显示,美沙拉嗪能有效降低小鼠结肠组织的组织学评分,合用灌肠液可以加强这一作用;采用酶联免疫吸附测定方法检测小鼠结肠组织中肿瘤坏死因子-α、干扰素-γ以及白细胞介素-6的含量,灌肠液能增强美沙拉嗪对炎性因子的下调作用;采用蛋白质免疫印迹试验法检测小鼠结肠组织中凋亡基因cleaved caspase-3,Bax,Bcl-2的表达情况,灌肠液可增强美沙拉嗪对cleaved caspase-3、Bax蛋白的上调作用和对Bcl-2蛋白的下调作用。结论 联合应用中药灌肠液能增强美沙拉嗪对小鼠溃疡性结肠炎的治疗作用、对炎性因子和细胞凋亡的抑制作用,为临床联合应用提供理论依据。
The Mechanism of a Traditional Chinese Medicine Enema in the Adjuvant Treatment of Ulcerative Colitis
Objective To investigate the protective and adjuvant therapeutic effects of a traditional Chinese medicine enema preparation against ulcerative colitis in mice based on molecular pharmacology.Methods A mouse model of ulcerative colitis induced by dextran sulfate sodium salt was constructed before the mice were randomly divided into the normal control group,model control group,mesalazine group,and mesalazine + enema solution group.The mice except those in the normal control group drank 4%dextran sulfate sodium salt aqueous solution freely for 7 days.The mesalazine + enema liquid group was given 0.52 g·kg-1 mesalazine by gavage every day,and self-made Chinese medicine preparations were used as an enema each morning and evening.The mesalazine group was given 0.52 g·kg-1 mesalazine by gavage every day,and a normal saline enema each morning and evening.The normal control group and the model control group were gavaged with normal saline every day,plus a normal saline enema every morning and evening for 14 consecutive days before the colonic tissues were frozen for later use.Results Ulcerative colitis could significantly reduce the body weight of mice,which could be reversed by mesalazine,and the effect of the mesalazine + enema liquid group was better than that of the mesalazine group.The results of hematoxylin-eosin staining and histological scoring showed that mesalazine could effectively reduce the histological score of colon tissues in mice,and this effect could be enhanced by the combined use of enema fluid.The contents of TNF-α,INF-γ and IL-6 in mouse colon tissues were detected with ELISA,and the enema fluid could synergistically enhance the down-regulation of mesalazine on inflammatory factors.The expressions of apoptotic genes cleaved caspase-3,Bax and Bcl-2 in mouse colon tissues were detected by Westen blot,and the enema fluid could synergistically enhance the up-regulation of mesalazine on cleaved caspase-3 and Bax proteins and the down-regulation of Bcl-2 proteins.Conclusion The combined use of traditional Chinese medicine enema liquid can synergistically enhance the therapeutic effect of mesalazine against mouse colon tissues,enhance the inhibitory effect of mesalazine on inflammatory factors,and enhance the inhibitory effect of mesalazine on apoptosis.

ulcerative colitistraditional Chinese medicine enemainflammatory responseapopto-sismice

门敬菊、杨晓波、白成、李海霞、刘丹

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116021 辽宁大连,联勤保障部队第967医院

116044 辽宁大连,大连医科大学药学院

溃疡性结肠炎 中药灌肠制剂 炎症反应 凋亡 小鼠

2024

解放军药学学报
中国人民解放军总后勤部卫生部 药品仪器检验所

解放军药学学报

影响因子:0.529
ISSN:1008-9926
年,卷(期):2024.37(1)
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