机构地区:[1]河南中医药大学第二临床医学院,河南郑州450002 [2]河南省中医院,河南郑州450002 [3]黄河科技学院,河南郑州450002
出 处:《时珍国医国药》2024年第9期2117-2121,共5页Lishizhen Medicine and Materia Medica Research
基 金:国家自然科学基金青年基金(82104833);全国名老中医药专家传承工作室([2022]3号);河南省中医药科学研究专项课题(20-21ZY2114,2024ZYD05,2024ZY2084,2022ZY1086);河南省科技攻关项目(212102310339,242102311259);河南省卫生健康委员会河南省中医药学科领军人才培养项目([2021]8号)。
摘 要:目的基于高迁移率族蛋白B1(HMGB1)/晚期糖基化终末产物受体(RAGE)信号通路研究炎调方保护脓毒症急性胃肠损伤(AGI)大鼠的作用机制。方法共选取90只SD大鼠,随机分成假手术组、模型组、炎调方高剂量(29.6g/kg)组、中剂量(14.8g/kg)组和低剂量(7.4g/kg)组,每组18只。除假手术组外,均建立脓毒症AGI模型。用药后观察大鼠生存率;对大鼠的肠道肌电活动情况以及肠道内大肠埃希菌、双歧杆菌、乳酸杆菌的含量进行了测定;用苏木素-伊红染色(HE)法测定各组大鼠肠黏膜组织的病理改变;采用ELISA法测定TNF-α、IL-6的含量;免疫组化测定Claudin-1、ZO-1蛋白含量;采用QRT-PCR法对HMGB1、RAGE的mRNA表达情况进行检测。结果与模型组对比,随着炎调方剂量增加,各组大鼠生存率、肠道平滑肌的慢波频率与振幅、肠黏膜的厚度与绒毛高度、肠道内双歧杆菌与乳酸杆菌的含量、回肠组织Claudin-1、ZO-1蛋白的表达均有显著提升(P<0.05)。同时,大鼠血清中的TNF-α、IL-6水平、肠道大肠杆菌含量、以及HMGB1与RAGE的mRNA表达量均有显著下降(P<0.05),差异存在统计学意义(P<0.05)。结论炎调方具有改善脓毒症AGI大鼠肠黏膜损伤、抑制炎症反应和恢复肠道内环境稳态的能力,这可能与炎调方通过HMGB1/RAGE信号轴来调节肠道屏障功能有关。Objective To investigate the mechanism of action of inflammation-modulating formula based on the high mobility group protein B1(HMGB1)/receptor for advanced glycosylation end-products(RAGE)signalling pathway to protect septic a-cute gastrointestinal injury(AGI)rats.Methods A total of 90 SD rats were selected and randomly divided into sham-operation group,model group,high dose(29.6g/kg)group,medium dose(14.8g/kg)group and low dose(7.4g/kg)group of Inflam-mation Regulation Formula,with 16 rats in each group.The AGI model of sepsis was established,except in the sham-operated group,and the survival rate of rats was observed after drug administration;the intestinal myoelectric activity and the contents of Escherichia coli,Bifidobacterium bifidum,and Lactobacillus lactis in the intestinal tract of rats were determined;the pathological changes of the intestinal mucosal tissues of the rats in each group were measured by Hematoxylin-Eosin Staining(HE)method;the levels of TNF-αand IL-6 were determined using ELISA;the levels of Claudin-1 and ZO-1 proteins were determined by immunohistochemistry;and the mRNA expression of HMGB1 and RAGE was examined using QRT-PCR method.Results Com-pared with the model group,with the increase of the dose of Inflammation Regulation Formula,the survival rate,the slow wave frequency and amplitude of intestinal smooth muscle,the thickness of intestinal mucosa and the height of villi,the content of Bifidobacterium and Lactobacillus in the intestinal tract,and the expression of Claudin-1 and ZO-1 proteins in ileal tissues of the rats in the various groups were significantly elevated(P<0.05).Meanwhile,there was a statistically significant(P<0.05)decrease in the levels of TNF-αand IL-6 in rat serum,the content of E.coli in the intestinal tract,as well as the mRNA ex-pression of HMGB1 and RAGE.Conclusion The ability of Inflammation Tuning Formula to ameliorate intestinal mucosal injury,inhibit inflammatory response and restore homeostasis of intestinal internal environment in septic AGI rats may be
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