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洗心汤对快速老化模型小鼠Th17/Treg细胞免疫平衡及相关转录因子表达的影响 被引量:2

Xixin Decoction regulates Th17/Treg balance and transcription factor expression in senescence-accelerated mouse-prone
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摘要 探讨洗心汤对快速老化模型(SAMP8)小鼠肠黏膜辅助性T细胞17(T helper 17 cell,Th17)/调节性T细胞(regulatory T cell,Treg)免疫平衡及相关转录因子表达的影响。50只14周龄的雄性SAMP8小鼠按随机数字表法分为模型组,益生菌组,洗心汤高、中、低剂量组,每组10只。10只14周龄的雄性抗快速老化(SAMR1)小鼠作为对照组。喂养10周后开始连续灌胃10周。Morris水迷宫实验检测小鼠学习记忆能力;酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)检测小鼠肠黏膜SIgA(secretory immunoglobulin A)含量;流式细胞术检测小鼠肠黏膜Th17、Treg含量;蛋白免疫印迹法(Western blot)检测小鼠结肠组织视黄酸相关孤儿受体γt(retinoic acid related orphan receptor-γt,RORγt)、叉头盒蛋白p3(forkhead box p3,Foxp3)蛋白的表达。结果显示,与对照组相比,模型组小鼠逃避潜伏期明显延长(P<0.01),60 s内穿越平台次数及目标象限停留时间显著减少(P<0.01);肠黏膜SIgA含量显著降低(P<0.01),Th17含量升高(P<0.05),Treg含量降低(P<0.01);结肠中RORγt蛋白表达明显升高(P<0.01),Foxp3蛋白表达明显降低(P<0.01)。与模型组相比,洗心汤高剂量组小鼠学习记忆能力明显提高(P<0.05或P<0.01);益生菌组,洗心汤高、中剂量组小鼠肠黏膜SIgA含量明显升高(P<0.05或P<0.01),Th17含量降低(P<0.05或P<0.01),Treg含量升高(P<0.05或P<0.01);结肠中RORγt蛋白表达明显降低(P<0.01),Foxp3蛋白表达明显升高(P<0.01)。结果表明,洗心汤可能通过促进SIgA分泌、调节Th17/Treg细胞免疫平衡以及改善RORγt和Foxp3蛋白表达,从而作用于肠道黏膜免疫屏障,影响阿尔茨海默病肠脑信息交换,改善SAMP8小鼠学习记忆能力。 This study aims to investigate the effect of Xixin Decoction on the T helper 17 cell(Th17)/regulatory T cell(Treg)balance of intestinal mucosa and the expression of related transcription factors in the senescence-accelerated mouse-prone 8(SAMP8)model.Fifty 14-week male mice of SAMP8 were randomized by the random number table method into model group,probiotics group,and high-,medium-,and low-dose Xixin Decoction groups,with 10 mice in each group.Ten 14-week male mice of senescence-accelerated mouse-resistant 1(SAMR1)served as control group.After 10 weeks of feeding,the mice were administrated with corresponding drugs for 10 weeks.Morris water maze test was carried out to examine the learning and memory abilities of mice.Enzyme-linked immunosorbent assay(ELISA)was employed to determine the content of secretory immunoglobulin A(SIgA)in the intestinal mucosa,and flow cytometry to detect the percentage content of Th17 and Treg in the intestinal mucosa.Western blot was performed to determine the protein levels of retinoid-related orphan receptor gamma t(RORγt)and forkhead box p3(Foxp3)in the mouse colon tissue.Compared with control group,the escape latency of mice in model group was significantly prolonged(P<0.01),and the number of times of crossing the platform and the residence time in the target quadrant were significantly reduced within 60 s(P<0.01),intestinal mucosal SIgA content was significantly decreased(P<0.01),Th17 content was increased(P<0.05),Treg content was decreased(P<0.01),the expression of RORγt protein was increased and Foxp3 protein was decreased in colon(P<0.01).Compared with the model group,high-dose Xixin Decoction group improved the learning and memory ability(P<0.05 or P<0.01).Probiotics group and high-and medium-dose Xixin Decoction group increased the content of SIgA in intestinal mucosa(P<0.05 or P<0.01),decreased percentage content of Th17 and increased the percentage content of Treg in intestinal mucosa(P<0.05 or P<0.01).Furthermore,they down-regulated the protein level of RORγt and up-regulated the protein level of Foxp3 in the intestinal mucosa(P<0.01).In conclusion,Xixin Decoction may act on intestinal mucosal immune barrier,affect gut-brain information exchange,and improve the learning and memory ability of SAMP8 by promoting SIgA secretion and regulating the Th17/Treg balance and the expression of RORγt and Foxp3.
作者 张虎 第五永长 赵恩龙 段力琦 韩欣悦 王登坤 刘奇 周源 ZHANG Hu;DIWU Yong-chang;ZHAO En-long;DUAN Li-qi;HAN Xin-yue;WANG Deng-kun;LIU Qi;ZHOU Yuan(the First Clinical Medical College,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Shaanxi University of Chinese Medicine,Xianyang 712046,China)
出处 《中国中药杂志》 CAS CSCD 北大核心 2024年第5期1353-1360,共8页 China Journal of Chinese Materia Medica
基金 国家自然科学基金项目(82074503) “陕西中医药大学神经退行性疾病中医药防治研究学科创新团队”项目(2019-QN05) 陕西省“特支计划”科技创新领军人才项目(陕组通字[2018]33号)。
关键词 洗心汤 阿尔茨海默病 Th17/Treg平衡 Xixin Decoction Alzheimer′s disease Th17/Treg balance
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