首页|心理应激相关非酒精性脂肪性肝病小鼠模型的建立及四逆散的治疗效应研究

心理应激相关非酒精性脂肪性肝病小鼠模型的建立及四逆散的治疗效应研究

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目的 建立心理应激相关非酒精性脂肪性肝病小鼠模型并探讨四逆散的治疗效应.方法 40只雄性C57 BL/6J小鼠随机区分为空白组(CON)、高蔗糖富含胆固醇饮食组(CHR)、复合模型组(CS+CHR)、百洛特组(BLT)、四逆散组(SNS).除CON组外,其余各组小鼠均给予CHR饮食,且CS+CHR组、BLT组、SNS组每天随机给予2种不同应激,共60d.BLT组、SNS组于造模后30 d进行灌胃给药.观察小鼠行为学变化,计算肝指数、胸腺指数、脂肪指数,检测肝组织TC、TG含量,油红O、HE染色观察肝组织病理改变,检测血清皮质酮(CORT)、醛固酮(ALD)、胰岛素(INS)、胰高血糖素(GCG)含量.结果 与CON组相比,CHR组脂肪指数、TC含量升高(P<0.05),CS+CHR组直立次数下降(P<0.05),脂肪指数及TC、TG、CORT、ALD、GCG含量显著增高(P<0.01);与CHR组相比,CS+CHR组直立次数下降(P<0.05),TC、TG、ALD、INS、GCG含量显著增高(P<0.01);与CS+CHR组相比,SNS散组直立次数回升(P<0.05),TG、ALD含量显著降低(P<0.01),BLT组脂肪指数、TC含量降低(P<0.05),ALD含量显著降低(P<0.01).油红0染色结果显示,CS+CHR组可见少量脂滴,BLT组与SNS组均有减轻;而HE石蜡染色结果显示,CHR组可见少量大小不等、数量不一的圆形空泡,部分肝细胞核被挤压向肝细胞一侧,CS+CHR组可见大量大小不等、数量不一的圆形空泡,脂滴数量较多,部分肝细胞核被挤压向肝细胞一侧,而BLT组与SNS组均有减轻.结论 CUMS联合CHR饮食可以更好地构建心理应激相关NAFLD小鼠模型,四逆散改善此疾病可能与其降低血清醛固酮含量相关.
Establishment of Mouse Model of Non-Alcoholic Fatty Liver Disease Related to Psychological Stress and The Therapeutic Effect of Sini Powder(四逆散)
Objective To establish a mouse model of non-alcoholic fatty liver disease related to psychological stress and to explore the therapeutic effect of Sini Powder(四逆散).Methods Forty male C57BL/6J mice were randomly divided into blank group(CON),high sucrose rich cholesterol diet group(CHR),compound model group(CS+CHR),paracetamol group(BLT)and Sini Powder group(SNS).Except CON group,all the other groups were given CHR diet,and CS+CHR group,BLT group and SNS group were randomly given two different kinds of stress every day for 60 days.BLT group and SNS group were given intragastric administration 30 days after the establishment of the model.The behavioral changes of mice were observed,the liver index,thymus index and fat index were calculated,the contents of total cholesterol(TC)and triglyceride(TG)in liver tissue were detected,the pathological changes of liver tissue were observed by oil red O and HE staining,and the contents of serum corticosterone(CORT),aldosterone(ALD),insulin(INS)and glucagon(GCG)were measured.Results Compared with those of the CON group,fat index and TC content of the CHR group increased,the upright times of the CS+CHR group decreased,fat index and the levels of TC,TG,CORT,ALD and GCG significantly increased.The upright times of the CS+CHR group decreased,the levels of TC,TG,ALD,INS and GCG significantly increased compared with those of the CHR group.Compared with those of the CS+CHR group,the upright times of the SNS Powder group increased,the contents of TG and ALD decreased significantly,and the fat index,the levels of TC content and ALD decreased significantly in the BLT group.Oil red O staining showed that a small number of lipid droplets could be seen in the CS+CHR group,and reduced in BLT group and SNS group,while HE paraffin staining showed that a small number of round vacuoles of different sizes and numbers were seen in the CHR group,and some round vacuoles were squeezed to one side of hepatocytes in the CS+CHR group,and a large number of lipid droplets were found in the CS+CHR group,and some liver nuclei were squeezed to one side of hepatocytes in BLT group and SNS group.Conclusion CUMS combined with CHR diet can better establish the model of psychological stress-related NAFLD mice.Sini Powder may improve the disease by reducing the content of serum aldosterone.

chronic mild unpredictable modelnon-alcoholic fatty liver diseasepsychological stressSini Powder(四逆散)aldosterone

邵奇、李婷、马重阳、陈思敏、孙资金、程发峰

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北京中医药大学中医学院,北京市重点实验室,北京 100105

北京中医药大学东直门医院,北京 100007

首都医科大学中医学院,北京 100029

慢性温和不可预知模型 非酒精性脂肪性肝病 心理应激 四逆散 醛固酮

2025

辽宁中医杂志
辽宁中医药大学,辽宁省中医药学会

辽宁中医杂志

北大核心
影响因子:0.815
ISSN:1000-1719
年,卷(期):2025.52(1)