逍遥丸对代谢相关脂肪性肝炎CYP2E1及FasL/TNF-α信号通路的影响  

Effect of Xiaoyao Wan on CYP2E1 and FasL/TNF-αsignal pathway in metabolic associated steatohepatitis

作　　者：张馨月 张玉伟 李梦琪 孟雅楠 李若瑜 苗宇船 Zhang Xinyue;Zhang Yuwei;Li Mengqi;Meng Yanan;Li Ruoyu;Miao Yuchuan(Dept of Pathology,Shanxi University of Chinese Medicine,Jinzhong 030619;Dept of Encephalopathy,Shanxi University of Chinese Medicine Affiliated Hospital,Taiyuan 030000)

机构地区：[1]山西中医药大学病理教研室,晋中030619 [2]山西中医药大学附属医院脑病科,太原030000

出　　处：《安徽医科大学学报》2024年第7期1218-1224,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81470190);山西省卫生健康委项目(编号:2019089);山西中医药大学科技创新能力培育计划“基础研究专项”项目(编号:2021PY-JC-04);山西中医药大学风湿免疫性疾病中西医结合基础学科建设项目(编号:2023XKJS-03)。

摘　　要：目的研究逍遥丸治疗代谢相关脂肪性肝炎(MASH)大鼠的机制。方法24只雄性SD大鼠随机分为对照组(CON组,n=8)和模型组(n=16),模型组给予高脂饮食+四氯化碳背部皮下注射+饥饱失常+夹尾,联合刺激4周建立MASH模型,再随机分为MOD组和逍遥丸组(XYW组),每组各8只。XYW组大鼠给予逍遥丸灌胃,其他两组给予0.9%氯化钠溶液灌胃。给药4周后,对不同组别大鼠的血清生化及氧化应激指标进行检测。HE染色和油红O染色对大鼠肝组织进行病理切片观察。Western blot对大鼠肝脏中细胞色素P4502E1(CYP2E1)、凋亡相关因子配体(FasL)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)的表达进行检测。RT-qPCR检测肝组织CYP2E1、FasL、TNF-α、TGF-β1 mRNA相对含量。结果XYW组大鼠的一般情况较MOD组有显著改善,肝指数较MOD组下降(P<0.01),体质量指数较MOD组上升(P<0.01);XYW组血清中三酰甘油、总胆固醇、低密度脂蛋白胆固醇、天冬氨酸氨基转氨酶、丙氨酸氨基转移酶、丙二醛、单核细胞趋化蛋白-1、TNF-α、白细胞介素(IL)-18水平较MOD组降低(均P<0.05),高密度脂蛋白胆固醇、超氧化物歧化酶、IL-10水平较MOD组升高(均P<0.05);光镜下可观察到XYW组肝细胞内脂滴含量较MOD组明显减少;XYW组肝组织CYP2E1、FasL、TNF-α、TGF-β1的蛋白水平较MOD组降低(均P<0.05),CYP2E1、FasL、TNF-α、TGF-β1 mRNA相对含量较MOD组降低(均P<0.05)。结论逍遥丸通过调节CYP2E1、FasL、TNF-α、TGF-β1在MASH大鼠肝组织中的转录表达,减少肝脏脂肪酸蓄积,从而达到治疗MASH的目的。Objective To study the mechanism of the treatment of metabolism associated steatohepatitis(MASH)in rats with Xiaoyao Wan.Methods Twenty-four SD male rats were randomly divided into control group(CON group,n=8)and model group(n=8).The model group was given high-fat diet,carbon tetrachloride(CCl 4)subcutaneous injection,hunger and satiety disorder and tail clamping for four weeks to establish the MASH model,and the rats were randomly divided into the MOD group and the Xiaoyao Wan group(XYW group),with 8 rats in each group.The rats of the XYW group were given Xiaoyao Wan,the other two groups were given normal saline.Four weeks after administration,the serum biochemical indexes and oxidative stress indexes of rats in different groups were detected.The pathological sections of rat liver tissue were observed by hematoxylin-eosin(HE)staining and oil red O staining.The expression of cytochrome P4502E1(CYP2E1),factor-related apoptosis ligand(FasL),tumor necrosis factor-α(TNF-α)and tumor growth factor-β1(TGF-β1)in rat liver were detected by Western blot method.The relative contents of CYP2E1,FasL,TNF-αand TGF-β1 mRNA in liver tissue were detected by RT-qPCR.Results The general condition of rats in the XYW group was significantly improved compared with the MOD group;the level of hepatic index was significant decrease compared with the MOD group(P<0.01)and the level of body mass index was significant increase compared with the MOD group(P<0.01);the serum levels of triglyceride,total cholesterol,low-density lipoprotein cholesterol,aspartate aminotransferase,alanine aminotransferase,malondialdehyde,monocyte chemotactic protein-1,TNF-α,and interleukin(IL)-18 were significantly reduced compared with the MOD group(all P<0.05),and the levels of high-density lipoprotein cholesterol,superoxide dismutase,and IL-10 were significantly elevated compared with the MOD group(all P<0.05);the content of lipid droplets in hepatocytes of rats was significantly reduced compared with the MOD group under light microscope;the protein levels

关 键 词：逍遥丸 代谢相关脂肪性肝炎 细胞色素P4502E1 凋亡相关因子配体 肿瘤坏死因子-α 转化生长因子-β1 

分 类 号：R575.5[医药卫生—消化系统] R589.2[医药卫生—内科学]