辣椒素保护肠黏膜屏障改善酒精性肝病小鼠肝损伤的实验研究  

Experimental study on capsaicin improving liver damage in mice with alcoholic liver disease by protecting intestinal mucosal barrier

作　　者：马文婷 陶乐 刘旭凌[1] 叶军[1] 吴柳 杨广越 张玮 刘成[2] MA Wenting;TAO Le;LIU Xuling;YE Jun;WU Liu;YANG Guangyue;ZHANG Wei;LIU Cheng(Hepatology Laboratory,Department of Infectious Diseases,Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China;Central Laboratory,Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200062,China)

机构地区：[1]上海中医药大学附属普陀医院感染科肝病实验室,上海200062 [2]上海中医药大学附属普陀医院中心实验室,上海200062

出　　处：《上海中医药杂志》2022年第5期54-59,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81803232,81873136,81803898,82004106);上海市卫健委卫生行业临床研究专项(202040149);上海市普陀区卫生系统自主创新科学基金项目(ptkwws201904);上海市普陀区卫生健康系统科技创新项目(ptkwws202223)

摘　　要：目的研究辣椒素对酒精性肝病小鼠肝脏和肠黏膜病变的改善作用,并探讨其作用机制。方法24只雄性C57/BL6小鼠随机分为对照组、乙醇组和乙醇辣椒素组,乙醇组及乙醇辣椒素组采用4周慢性乙醇液体饲料喂养加急性乙醇灌胃法复制酒精性肝病小鼠模型,对照组给予等量液体饲料。造模第3周起,乙醇辣椒素组给予辣椒素(10 mg/kg)灌胃,隔日1次,每周3次,其余两组给予等体积蒸馏水灌胃。造模4周结束后,乙醇组及乙醇辣椒素组给予31.5%乙醇灌胃,对照组给予45%糊精灌胃,9 h后处死小鼠,留取血、肝脏、小肠组织样本。检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和三酰甘油(TG)含量;苏木精-伊红(HE)染色观察肝脏和小肠黏膜病理变化,油红染色观察肝脏脂质沉积情况。采用RT-PCR检测肝脏炎症因子肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)及小肠组织炎症因子TNF-α、IL-6、单核细胞趋化蛋白-1(MCP-1)及紧密连接蛋白中闭合小环蛋白-1(ZO-1)、咬合蛋白(occludin)、闭合蛋白-1(claudin-1)的mRNA表达水平。结果与对照组比较,乙醇组小鼠ALT、AST和TG水平显著升高(P<0.05);肝脏组织中TNF-α、IL-6、IL-1βmRNA均显著升高(P<0.05)。HE染色可见乙醇组小鼠肝脏脂肪变性及炎细胞浸润明显,油红染色显示乙醇组小鼠肝细胞内有大量脂滴。小肠HE染色可见乙醇组小肠绒毛高度缩短,上皮细胞水肿,黏膜下炎细胞浸润增多。乙醇组小鼠小肠组织TNF-α、IL-6、MCP-1mRNA水平较对照组显著升高(P<0.05),而紧密连接蛋白的ZO-1、occludin、claudin-1 mRNA水平则较对照组显著降低(P<0.01)。与乙醇组比较,乙醇辣椒素组小鼠ALT、AST和TG水平显著减低(P<0.05),肝脏组织中TNF-α、IL-6、IL-1βmRNA均显著减低(P<0.05),肝脏脂肪变及肠黏膜病理损伤均减轻,肠黏膜TNF-α、IL-6、MCP-1 mRNA水平明显降低(P<0.05),而紧密连接蛋白的ZO-1、occluObjective To study the effect of capsaicin on the improvement of liver and intestinal mucosal lesions in mice with alcoholic liver disease(ALD),and explore its related mechanisms.Methods Twenty-four male C57/BL6 mice were randomly divided into the control group,the alcohol group and the alcohol capsaicin group.The mice in the alcohol group and the alcohol capsaicin group were fed with ethanol liquid diet for 4 weeks and gavaged with alcohol to replicate the alcoholic liver disease model.The control group was administered with isocaloric liquid feed.From the 3rd week of modeling,the alcohol capsaicin group was given capsaicin(10 mg/kg body weight)by gavage every other day and three times a week,while the other two groups were given an equal volume of distilled water by gavage.After 4 weeks of modeling,mice in the alcohol group and the alcohol capsaicin group were given 31.5%ethanol by gavage,while the mice in the control group were given 45%dextrin by gavage.The mice were sacrificed 9 hours later,and blood,liver and small intestine tissue samples were collected.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels were detected by enzyme-linked immunosorbent assay.The pathological changes of liver and small intestine mucosa were observed after HE staining.The lipid deposition in the liver was observed by oil red O staining.RT-PCR was used to detect the mRNA expression levels of liver inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin 6(IL-6),interleukin 1β(IL-1β),small intestinal tissue inflammatory factors including TNF-α,IL-6,monocyte chemoattractant protein 1(MCP-1)and tight junction proteins including ZO-1,occludin and claudin-1.Results Compared with the control group,the serum ALT,AST,TG levels and liver mRNA expressions of TNF-α,IL-6,IL-1βwere significantly increased in the alcohol group(P<0.05).HE staining showed that hepatic steatosis and inflammatory cells in the alcohol group was obvious.Oil red staining showed a large number of lipid

关 键 词：辣椒素 酒精性肝病 肠黏膜屏障 模型小鼠 中药研究 

分 类 号：R285.5[医药卫生—中药学]