葛根芩连汤对抗生素相关性腹泻大鼠模型肠系膜淋巴结IRF4与XBP-1的影响  

Effects of Gegen Qinlian Decoction on IRF4 and XBP-1 in Mesenteric Lymph Nodes of a Rat Model with Antibiotic-Associated Diarrhea

作　　者：杨光勇 韩晴 樊丽莎 潘燚 苏刚 张庚鑫 何光志 YANG Guangyong;HAN Qing;FAN Lisha;PAN Yi;SU Gang;ZHANG Gengxin;HE Guangzhi(College of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025

出　　处：《中医药学报》2024年第11期11-16,共6页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金地区科学基金项目(82060796);贵州省科学技术厅科技科学技术基金(黔科合基础〔2020〕1Y392)。

摘　　要：目的:探究葛根芩连汤对抗生素相关性腹泻(AAD)大鼠模型肠系膜淋巴结干扰素调节因子4(IRF4)与X-盒结合蛋白1(XBP-1)的影响。方法:SD大鼠180只,随机取150只用于制备AAD模型,给予克林霉素(250 mg/kg)灌胃,1次/d,持续给药7 d,剩余30只作为正常组并灌胃等体积生理盐水。造模成功后随机分为5组,即模型组、葛根芩连汤高(GQD-H组,10.08 g/kg)、中(GQD-M组,5.04 g/kg)、低剂量组(GQD-L组,2.52 g/kg)和双歧杆菌活性菌胶囊组(双歧菌组,0.15 g/kg),每组30只。以上6组大鼠分别在灌胃后3 d、7 d、14 d每组随机取10只于麻醉后处死,提取结肠组织,分别采用HE染色法及免疫组化方法观察结肠组织形态及IRF4与XBP-1蛋白表达量变化,无菌条件下采集大鼠肠系膜淋巴结,提取淋巴结总RNA后经过反转录PCR合成cDNA,随后采用qPCR技术检测3 d、7 d、14 d不同持续给药时间段内葛根芩连汤对大鼠AAD模型中淋巴结IRF4与XBP-1 mRNA的表达水平。结果:3个时间段的检测结果均显示模型组结肠组织明显损伤,炎性细胞浸润,且IRF4与XBP-1 mRNA表达水平较正常组均显著上调(P<0.05),与模型组比较,葛根芩连汤高、中、低剂量组以及双歧杆菌活性菌胶囊组结肠组织均有不同程度恢复,且IRF4与XBP-1 mRNA表达水平较正常组均显著下调(P<0.05)。结论:葛根芩连汤可以降低因服用克林霉素导致的AAD引起的肠系膜淋巴结IRF4与XBP-1 mRNA高表达及结肠组织损伤,调节肠道炎症。Objective:To investigate the effects of Gegen Qinlian Decoction(GQD)on interferon regulatory factor 4(IRF4)and X-box binding protein 1(XBP-1)in the mesenteric lymph nodes of a rat model with antibiotic-associated diarrhea(AAD).Methods:A total of 180 SD rats were used,with 150 randomly selected to establish the AAD model through gavage with clindamycin(250 mg/kg),administered once daily for 7 days.The remaining 30 rats served as the normal group and received an equivalent volume of saline.Post-modeling,rats were randomly divided into five groups:model group,high-dose GQD group(GQD-H,10.08 g/kg),medium-dose GQD group(GQD-M,5.04 g/kg),low-dose GQD group(GQD-L,2.52 g/kg),and Bifidobacterium active bacterial capsule group(Bifidobacterium group,0.15 g/kg),with 30 rats in each group.Rats in each group were euthanized at 3,7,and 14 days post-gavage,with colon tissues extracted for morphological examination via HE staining and immunohistochemical analysis of IRF4 and XBP-1 protein expression.Mesenteric lymph nodes were collected under sterile conditions to extract total RNA,and cDNA was synthesized via reverse transcription PCR.The expression levels of IRF4 and XBP-1 mRNA were detected by qPCR at 3,7,and 14 days of continuous administration.Results:At all three time points,the model group exhibited significant colon tissue damage and inflammatory cell infiltration,with IRF4 and XBP-1 mRNA expression levels significantly upregulated compared to the normal group(P<0.05).In comparison to the model group,the GQD high,medium,and low-dose groups,as well as the Bifidobacterium group,showed varying degrees of tissue recovery and significantly downregulated IRF4 and XBP-1 mRNA expression levels(P<0.05).Conclusion:Gegen Qinlian Decoction can mitigate the high expression of IRF4 and XBP-1 mRNA and colon tissue damage induced by clindamycin in AAD,thereby modulating intestinal inflammation.

关 键 词：葛根芩连汤 抗生素相关性腹泻 X-盒结合蛋白1 干扰素调节因子4 

分 类 号：R285.5[医药卫生—中药学]