降脂颗粒通过减轻脂肪组织功能障碍改善小鼠非酒精性脂肪性肝炎  

Jiangzhi Granule improves nonalcoholic steatohepatitis in mice through alleviating adipose tissue dysfunction

作　　者：陈智炜 宋海燕 黄萍 杨丽丽 王珏 廖心怡 杨悦 郑培永 CHEN Zhiwei;SONG Haiyan;HUANG Ping;YANG Lili;WANG Jue;LIAO Xinyi;YANG yue;ZHENG Peiyong(Institute of Digestive Diseases,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院脾胃病研究所,上海200032

出　　处：《上海中医药大学学报》2022年第6期51-58,共8页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82174287,81704018);上海市自然科学基金项目(21ZR1463900)。

摘　　要：目的:基于脂肪组织功能障碍研究降脂颗粒改善非酒精性脂肪性肝炎(NASH)的作用及机制。方法:C57BL/6J小鼠给予高脂饲料联合高果糖/葡萄糖饮水HFCD-HF/G诱导10周,建立NASH模型;同时随机取8只正常小鼠,设为对照组,给予普通饲料。造模后,模型小鼠随机分为模型组、罗格列酮组及降脂颗粒高、低剂量组,每组8只。对照组小鼠给予普通饲料;其他组小鼠给予HFCD-HF/G,用药组同时每天灌胃给予相应药物。连续干预8周后,测定小鼠体质量、肝质量、附睾脂肪质量;试剂盒检测血清丙氨酸氨基转移酶(ALT)、总胆固醇(TC)水平;HE染色观察肝脏、脂肪组织病理学变化;流式细胞术检测小鼠附睾脂肪组织中巨噬细胞数量和M1/M2分型比例;RT-qPCR分析附睾脂肪组织炎性细胞因子肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10、单核细胞趋化蛋白-1(MCP-1)mRNA的表达水平,以及脂质代谢相关基因脂联素(ADIPOQ)、葡萄糖转运蛋白4(GLUT4)、脂肪酸结合蛋白4(FABP4)、磷酸烯醇式丙酮酸羧激酶1(PCK1)的表达水平。结果:①与对照组相比,模型组小鼠体质量、肝质量、附睾脂肪质量均明显增加(P<0.01)。与模型组相比,降脂颗粒各组小鼠体质量明显降低(P<0.05),降脂高剂量组小鼠肝质量明显降低(P<0.05),附睾脂肪质量有降低趋势;降脂颗粒各组小鼠血清ALT、TC水平明显下降(P<0.01)。②模型组出现大面积肝组织脂肪变,伴有肝小叶炎症和大量气球样变;降脂颗粒干预能明显改善这些病理变化,非酒精性脂肪性肝病活动度积分(NAS)评分明显下降(P<0.01)。③与模型组小鼠相比,降脂颗粒高剂量组小鼠附睾脂肪组织中脂肪细胞体积减小,炎细胞浸润减少。④降脂颗粒干预后,小鼠附睾脂肪组织巨噬细胞数量减少(P<0.05),M1/M2型巨噬细胞比例降低(P<0.05);促炎因子IL-6、MCP-1、TNF-α mRNA水平明显下降(P<0.05,P<0.01),抗炎因子IL-10 mRNA水平上升Objective:To explore the effect and mechanism of Jiangzhi Granule on nonalcoholic steatohepatitis(NASH)based on adipose tissue dysfunction.Methods:C57BL/6J mice were fed with high-fat and calorie diet plus high-fructose/glucose drinking water for 10 weeks to establish NASH mode,while 8 normal mice were randomly selected as the control group and given ordinary diet. After modeling,the model mice were randomly divided into model group,rosiglitazone group,low and high dose Jiangzhi Granule group(JZG-L and JZG-H group),with 8 mice in each group. Mice in the control group were given ordinary diet,mice in the other groups were given highfat diet,and mice in the treating groups were given corresponding drugs by gavage every day. After continuous intervention for 8 weeks,the body weight,liver weight and epididymis fat weight of mice were measured. The serum levels of alanine aminotransferase(ALT)and total cholesterol(TC)were measured by commercial kits. Histopathological changes of liver and adipose tissue were observed by HE staining.The number of macrophages and M1/M2 typing ratio in epididymal adipose tissue of mice were detected by flow cytometry. RT-qPCR was used to analyze the mRNA expression levels of inflammatory cytokines such as tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-10and monocyte chemotactic protein 1(MCP-1)in epididymal adipose tissue. The expression levels of lipid metabolism related genes including adiponectin(ADIPOQ),glucose transporter 4(GLUT4),fatty acid binding protein 4(FABP4)and phosphoenolpyruvate carboxykinase 1(PCK1)were also analyzed.Results:① Compared with the control group,the body weight,liver weight and epididymal fat weight of mice in the model group significantly increased(P<0.01). Compared with the model group,the body weight of mice in the JZG-L and JZG-H group significantly decreased(P<0.05),the liver weight of mice in the JZG-H group significantly decreased(P<0.05),epididymal fat weight showed a downward trend;the serum levels of ALT and TC of mice in JZG-L and JZG-H group

关 键 词：降脂颗粒 非酒精性脂肪性肝炎 脂肪组织功能障碍 脂肪-肝脏对话 

分 类 号：R285.5[医药卫生—中药学]