疏肝理脾汤对非酒精性脂肪性肝炎大鼠肠道菌群的影响  

Effects of Shugan Lipi decoction on intestinal flora in non-alcoholic steatohepatitis rats

作　　者：石媛媛 王雅[1] 郭丹 钟航宇 郑云杰 张涛[1] SHI Yuan-yuan;WANG Ya;GUO Dan;ZHONG Hang-yu;ZHENG Yun-jie;ZHANG Tao(Department of Hepatology,The First Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410007,Hunan Province,China)

机构地区：[1]湖南中医药大学第一附属医院肝病科,湖南长沙410007

出　　处：《中国临床药理学杂志》2024年第17期2533-2537,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金联合基金资助项目(U21A20413);湖南省自然科学基金资助项目(2022JJ30459);湖南省卫生健康委科研计划基金资助项目(B202303105937);湖南省中医药科研计划基金资助项目(B2023080)。

摘　　要：目的探讨疏肝理脾汤对非酒精性脂肪性肝炎(NASH)大鼠炎症及肠道菌群、Toll样受体4(TLR4)、T细胞免疫球蛋白黏蛋白-3(Tim-3)的影响。方法用蛋氨酸-胆碱缺乏饲料喂养4周建立NASH模型。将SD大鼠随机分为空白组(灌胃0.9%NaCl)、模型组(NASH模型,灌胃0.9%NaCl)、实验组(NASH模型,灌胃6.18 g·kg^(-1)疏肝理脾汤)。用Illumina边合成边测序法检测大鼠肠道微生物群16S rRNA序列,用蛋白质印迹法检测Tim-3和TLR4蛋白的表达水平,用酶联免疫吸附试验法检测各组大鼠肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL^(-1)0水平。结果用药4周后,空白组、模型组和实验组的拟杆菌门相对丰度分别为(47.96±10.52)%、(42.90±15.01)%和(57.15±10.99)%,厚壁菌门相对丰度分别为(49.27±9.99)%、(53.06±11.47)%和(39.99±11.88)%,Tim-3蛋白相对表达水平分别为1.03±0.07、0.24±0.06和1.57±0.11,TLR4蛋白相对表达水平分别为1.04±0.11、3.23±0.33和0.94±0.27,TNF-α水平分别为(403.03±25.25)、(576.87±60.29)和(385.16±37.67)pg·mL^(-1),IL-6水平分别为(125.35±14.07)、(189.75±34.30)和(113.71±18.35)pg·mL^(-1),IL^(-1)0水平分别为(123.20±15.96)、(66.71±11.94)和(119.54±10.57)pg·mL^(-1)。实验组的上述指标与模型组比较,在统计学上差异均有统计学意义(P<0.01,P<0.05)。结论疏肝理脾汤可能通过影响肠道菌群及TLR4、Tim-3蛋白表达来调控炎症因子,从而改善NASH。Objective To explore the effect of Shugan Lipi decoction on inflammation and intestinal flora,Toll like receptor 4(TLR4),T cell immunoglobulin domain and mucin domain-3(Tim-3)in non-alcoholic steatohepatitis(NASH)rats.Methods The NASH model was established by feeding methionine and choline deficient diet for 4 weeks.SD rats were randomly divided into blank group(intragastric administration with 0.9%NaCl),model group(NASH model,intragastric administration with 0.9%NaCl),and experimental group(NASH model,intragastric administration with 6.18g·kg-1 Shugan Lipi decoction).Illumina sequencing by synthesis method was used to detect the 16S rRNA sequence of rat Intestinal microbiota.Western blot method was used to detect the expression levels of Tim-3 and TLR4 proteins.Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL^(-1)0 levels in each gro up of rats.Results After 4 weeks of medication,the relative abundance of Bacteroidetes in the blank,model and experimental groups were(47.96±10.52)%,(42.90±15.01)%and(57.15±10.99)%;the relative abundance of Firmicutes were(49.27±9.99)%,(53.06±11.47)%and(39.99±11.88)%;the relative expression levels of Tim-3 protein were 1.03±0.07,0.24±0.06 and 1.57±0.11;the relative expression levels of TLR4 protein were 1.04±0.11,3.23±0.33 and 0.94±0.27;the levels of TNF-αwere(403.03±25.25),(576.87±60.29)and(385.16±37.67)pg·mL^(-1);the levels of IL-6 were(125.35±14.07),(189.75±34.30)and(113.71±18.35)pg·mL^(-1);the levels of IL^(-1)0 were(123.20±15.96),(66.71±11.94)and(119.54±10.57)pg·mL^(-1),respectively.The above indexes in the experimental group showed statistically significant differences compared with the model group(P<0.01,P<0.05).Conclusion Shugan Lipi decoction may regulate inflammatory cytokines by affecting intestinal flora and TLR4,Tim-3 protein expression,affect liver inflammatory response,and improve NASH.

关 键 词：疏肝理脾汤 非酒精性脂肪性肝炎 TOLL样受体4 T细胞免疫球蛋白黏蛋白-3 肠道菌群 炎症 

分 类 号：R28[医药卫生—中药学]