摘要
目的研究肝肺并治方对溃疡性结肠炎(Ulcerative Colitis UC)大鼠结肠组织NLRP3通路的影响。方法SD大鼠(SPF级)65只(雄性),随机分为对照组(10只),造模组(55只),造模组采用三硝基苯磺酸(Trinitrobenzenesulfonic acid solution TNBS)加乙醇灌肠法建立UC大鼠模型。随机选取5只造模组大鼠用以评价造模成功,其余50只随机分为模型组、Mesalazine组、肝肺并治方低、中、高剂量组5组。不同干预因素灌胃后采集大鼠一部分结肠组织制作病理切片,一部分提取组织蛋白采用Western-Blot法检测结肠黏膜NLRP3、ASC、Caspase-1、Gasdermin D蛋白、IL-1β、IL-18的蛋白表达水平。结果在溃疡性结肠炎大鼠模型中NLRP3、ASC、Caspase-1、IL-1β和IL-18均有不同程度的升高,而GSDMD降低。西药组对NLRP3、ASC和Caspase-1均有降低的作用,其中对NLRP3的作用最为显著。中药组的干预未明显降低NLRP3值,但其对ASC和Caspase-1的降低作用较西药组更为明显,其中中药中剂量组效果最佳。中药组和西药组对Caspase-1的干预效果相当,除中药中剂量组外西药组和其余中药组对于IL-1β的降低效果不明显,中药组和西药组均无明显降低IL-18的作用。GSDMD用药后则出现持续降低的趋势。结论肝肺并治方可调节溃疡性结肠炎大鼠NLRP3炎症小体,而其作用靶点在连接NLRP3与炎症因子的ASC和Caspase-1上。
Objective To study the effect of Ganfei Bingzhi Formula(肝肺并治方)onNOD-like receptor family pyrin domain containing 3(NLRP3)pathway in colonic tissue of ulcerative colitis(UC)rats.Methods Sixty-five male Sprague-Dawley rats(SPF grade)were randomly divided into control group(n=10)and model group(n=55).The model of UC rats was established by trinitrobenzenesulfonic acid solution(TNBS)and ethanol.Five rats were randomly selected to evaluate the success of modeling.The other 50 rats were randomly divided into 5 groups:model group,mesalazine group,Ganfei Bingzhi Formula low,middle and high dose group.After intragastric administration of different intervention factors,a part of colon tissue of the rats was collected to make pathological sections.The tissue protein was extracted by the other part of colon tissue of the rats,then the levels of protein expression of NLRP3,ASC,Caspase-1,Gasdermin D,interleukin-1β(IL-1β)and interleukin-18(IL-18)were detected with Western-Blot method.Results The levels of NLRP3,ASC,Caspase-1,IL-1βand IL-18 were increased in the UC rats,while GSDMD decreased.The levels of NLRP3,ASC and Caspase-1 were decreased in the western medicine group,and the effect on NLRP3 was the most significant.The intervention of the Chinese medicine group did not significantly reduce the NLRP3 value,but the reduction of ASC and Caspase-1 was more obvious than that of the mesalazinegroup.The effect of Ganfei Bingzhi Formula middle dose group was the best.The intervention effects on Caspase-1 in the Ganfei Bingzhi Formula groups and the mesalazine group were similar.The mesalazinegroup and the other Ganfei Bingzhi Formula groups had no obvious effect on the decrease of IL-1βexcept the Ganfei Bingzhi Formula middle dosegroup.The Ganfei Bingzhi Formula groups and the mesalazine group had no significant effect on reducing IL-18.GSDMD showed a trend of continuous decrease after medication.Conclusion Ganfei Bingzhi Formula can regulate NLRP3 inflammatory bodyin UC rats.Its targets are ASC and Caspase-1,which connect NLRP3 with inflammatory factors.
作者
杨丽
张继伟
臧思源
盖明辉
李忠卓
胡占起
YANG Li;ZHANG Jiwei;ZANG Siyuan;GAI Minghui;LI Zhongzhuo;HU Zhanqi(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110003,Liaoning,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,Liaoning,China)
出处
《辽宁中医杂志》
北大核心
2026年第2期193-198,I0005,I0006,共8页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金面上项目(82074449)
国家中医药管理局第七批全国老中医药专家学术经验继承工作项目(2022-2025)
辽宁省博士科研启动基金计划项目(2021-BS-177)
辽宁省教育厅面上项目(LJKZ0891)
辽宁省青年项目(JYTQN2023472)
沈阳市科学技术计划项目(22-321-33-46)
沈阳市公共卫生研发科技专项(医疗技术创新联合专项)项目(24-214-3-190)。
