【目的】 探讨穴位贴敷天枢穴联合温肾健脾法对溃疡性结肠炎（UC）患者临床疗效、肠道功能及 Toll样受体 4（TLR4）、 核因子κB（NF-κB）表达的影响。【方法】 选取2022年6月至2024年6月在上海中医药大学附属市中医医院肛肠科就诊的100例 UC脾肾亏虚兼湿邪内蕴证患者为研究对象，采用随机数字表法将患者随机分成A、B、C、D 4组，每组各25例。A组给予美沙 拉嗪标准治疗，B组给予温肾健脾方（由补骨脂、肉豆蔻、吴茱萸、五味子、党参、茯苓、白术等组成）联合美沙拉嗪标准治 疗，C组给予穴位贴敷天枢穴（贴敷药物由丁香、肉桂、白术、吴茱萸、黄连等组成）联合美沙拉嗪标准治疗，D组给予温肾 健脾方+穴位贴敷天枢穴+美沙拉嗪标准治疗，4组均给予连续治疗12周。比较4组患者的临床症状消失时间，观察4组患者 治疗前后血清炎症免疫细胞因子[β防御素 1（β-defensin-1）和总免疫球蛋白 A（IgA）、白细胞介素 6（IL-6）、肿瘤坏死因子 α （TNF-α）]、外周血 TLR4、NF-κB 水平及肠黏膜组织 TLR4 mRNA、NF-κB p65 mRNA 蛋白表达水平以及肠道菌群的变化情 况，并评价4组患者的临床疗效。【结果】（1）相较于其他3组，D组患者的腹痛、腹泻、黏液脓血便以及里急后重等临床症状 的消失时间最短（P＜0.05），而 B 组与 C 组患者的各项临床症状消失时间相近（P＞0.05），但均短于 A 组（P＜0.05）。（2）治疗 后，4组患者的血清 β-defensin-1、IgA、IL-6、TNF-α水平均较治疗前显著降低（P＜0.05）；且治疗后组间比较，差异均有 统计学意义（P＜0.01），其中以D组的降低幅度最大，且均显著低于其他3组（P＜0.05），而B组和C组的血清β-defensin-1、 IgA、IL-6、TNF-α水平相近（P＞0.05），但均低于 A组水平（P＜0.05）。（3）治疗后，4组患者外周血 TLR4、NF-κB水平及肠 黏膜组织TLR4 mRNA、NF-κB p65 mRNA蛋白表达水平均呈现下降趋势（P＜0.05）；且治疗后组间比较，差异均有统计学意 义（P＜0.01），其中以D组的降低幅度最大，且均显著低于其他3组（P＜0.05），而B组和C组的外周血TLR4、NF-κB水平及 肠黏膜组织 TLR4 mRNA、NF-κB p65 mRNA 蛋白表达水平相近（P＞0.05），但均低于 A 组水平（P＜0.05）。（4）治疗后，B组、 C组、D组患者的双歧杆菌、乳杆菌均增加（P＜0.05），酵母菌、梭菌均减少（P＜0.05）；且治疗后组间比较，差异均有统计 学意义（P＜0.01），其中D组的双歧杆菌、乳杆菌显著增加，酵母菌、梭菌显著减少，且其对双歧杆菌、乳杆菌的增加幅度 及对酵母菌、梭菌的减少幅度均显著优于其他 3组（P＜0.05），而 B组和 C组的双歧杆菌、乳杆菌、酵母菌、梭菌数量相似 （P＞0.05），但其改善幅度均显著优于A组（P＜0.05）。（5）治疗12周后，4组患者中以D组的总有效率最高，为100.00%（25/25）， 而B组和C组的总有效率相似，均为 84.00%（21/25），但均高于 A 组患者的 56.00%（14/25），组间比较，差异有统计学意义 （χ2 =16.310，P＜0.01）。【结论】 在美沙拉嗪标准治疗基础上给予穴位贴敷天枢穴联合温肾健脾方的综合治疗方案对 UC脾肾 亏虚兼湿邪内蕴证患者具有积极作用，该治疗方法能有效改善患者临床症状，调节β-defensin-1和IgA水平，增强免疫防御 功能，同时，还能下调TLR4、NF-κB的表达水平，减轻炎症反应，相比单一疗法，能更有效地提高治疗效果。

Objective To investigate the effects of acupoint application at Tianshu（ST25） combined with kidneywarming and spleen-invigorating therapy on clinical efficacy，intestinal function，and the expressions of Toll-like receptor 4（TLR4） and nuclear factor kappa-B （NF-κB） in patients with ulcerative colitis （UC）. Methods A total of 100 UC patients with depletion and deficiency of spleen-kidney complicated with internal accumulation of pathogenic dampness syndrome， treated in the Department of Proctology， Shanghai Municipal Hospital of Traditional Chinese Medicine Affilated to Shanghai University of Traditional Chinese Medicine from June 2022 to June 2024，were selected and randomly divided into four groups （Groups A，B，C，D） using a random number table method，with 25 patients in each group. Group A received standard mesalazine treatment. Group B received Kidney-Warming and Spleen-Invigorating Formula （composed of Psoraleae Fructus，Myristicae Semen，Euodiae Fructus，Schisandrae Chinensis Fructus，Codonopsis Radix，Poria，Atractylodis Macrocephalae Rhizoma，etc.） combined with standard mesalazine treatment. Group C received acupoint application at Tianshu（the medicinal paste for application composed of Caryophylli Flos， Cinnamomi Cortex， Atractylodis Macrocephalae Rhizoma， Euodiae Fructus， Coptidis Rhizoma， etc.） combined with standard mesalazine treatment. Group D received Kidney-Warming and Spleen-Invigorating Formula + acupoint application at Tianshu+ standard mesalazine treatment. All groups were treated continuously for 12 weeks. The time for disappearance of clinical symptoms was compared among the four groups. Serum immune cytokines [β-defensin-1，total immunoglobulin A （IgA），interleukin- 6（IL-6）， tumor necrosis factor-alpha （TNF- α）]， peripheral blood levels of TLR4 and NF- κB， protein expression levels of TLR4 mRNA and NF-κB p65 mRNA in intestinal mucosal tissue，and changes in intestinal microbiota were observed before and after treatment. The clinical efficacy of the four groups was evaluated. Results （1） Compared to the other three groups， Group D had the shortest time for disappearance of clinical symptoms such as abdominal pain，diarrhea，mucopurulent bloody stools，and tenesmus （P＜0.05）. The time for disappearance of various clinical symptoms in Groups B and C was similar （P＞0.05） but was shorter than that in Group A （P＜0.05）.（2） After treatment，the serum levels of β-defensin-1，IgA，IL-6，and TNF-α in all four groups were significantly lower than those before treatment （P＜0.05）. Post-treatment intergroup comparisons showed statistically significant differences （P＜0.01）， with Group D exhibiting the greatest reduction， significantly lower than the other three groups （P＜0.05）. The levels in Groups B and C were similar （P＞0.05） but were lower than those in Group A （P＜0.05）.（3） After treatment，the peripheral blood levels of TLR4 and NF-κB，and the protein expression levels of TLR4 mRNA and NF- κB p65 mRNA in intestinal mucosal tissue showed a decreasing trend in all four groups （P＜0.05）. Post-treatment intergroup comparison results were statistically significant （P＜0.01）， with Group D showing the greatest reduction， significantly lower than the other three groups （P＜0.05）. All above levels in Groups B and C were similar （P＞0.05） but were lower than those in Group A （P＜0.05）.（4） After treatment， the relative contents of Bifidobacterium and Lactobacillus increased （P＜0.05），while those of Saccharomyces and Clostridium decreased （P＜0.05） in Groups B，C，and D. Post-treatment intergroup comparison results were statistically significant （P＜0.01）. Group D showed a significant increase in Bifidobacterium and Lactobacillus and a significant decrease in Saccharomyces and Clostridium，with the magnitude of change significantly greater than that in the other three groups （P＜0.05）. The quantities of these bacteria in Groups B and C were similar （P＞0.05）， but the improvement was significantly greater than that in Group A （P＜0.05）.（5） After 12 weeks of treatment，Group D had the highest total effective rate at 100.00% （25/25）. The total effective rates of Groups B and C were similar，both at 84.00% （21/25），but were higher than that of Group A （56.00%，14/25）. The intergroup difference was statistically significant （χ2 = 16.310， P＜0.01）. Conclusion The comprehensive treatment regimen of acupoint application at Tianshu combined with Kidney-Warming and Spleen-Invigorating Formula，on the basis of standard mesalazine treatment，has a positive impact on UC patients with depletion and deficiency of spleen-kidney complicated with internal accumulation of pathogenic dampness syndrome. This treatment method can effectively improve clinical symptoms， regulate β-defensin-1 and IgA levels，enhance immune defense function，downregulate the expression levels of TLR4 and NF- κB， and alleviate inflammatory response. Compared to monotherapies， it is more effective on improving treatment outcomes.

R259.746

国家自然科学基金青年基金项目（编号：82305230）