机构地区:[1]陕西中医药大学基础医学院,陕西咸阳712046 [2]益阳医学高等专科学校,湖南益阳413000 [3]湖南中医药大学,湖南长沙410208
出 处:《中国病理生理杂志》2020年第7期1274-1280,共7页Chinese Journal of Pathophysiology
基 金:湖南省科技计划项目(No.2018JJ2412);湖南省中医药科研计划项目(No.201870);湖南省教育厅科学研究项目(No.17B271)。
摘 要:目的:探讨安化黑茶对高脂饮食诱导的载脂蛋白E敲除(ApoE^-/-)小鼠非酒精性脂肪肝的防治作用及相关机制。方法:选取8周龄雄性ApoE^-/-小鼠50只,随机分为模型组、阿托伐他汀组和安化黑茶高、中、低剂量组,每组10只,另选用10只8周龄C57BL/6J雄性野生小鼠作为正常对照组,ApoE^-/-和野生小鼠分别予以等量高脂饲料和普通饲料持续喂养17周,同时用相应药物或生理盐水灌胃干预。实验末取部分肝组织行HE染色,并检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)含量;RT-qPCR检测羟甲基戊二酸单酰辅酶A还原酶(HMGCR)、过氧化物酶体增殖物激活受体γ(PPAR-γ)和硬脂酰辅酶A脱饱和酶1(SCD-1)的mRNA表达。结果:模型组小鼠肝脏体积变大,表面光滑,被膜紧张,边缘变钝,肉眼呈现黄色油腻感,显微镜下可见大小不等的空泡形成,提示模型制备成功。与模型组相比,安化黑茶不同剂量组小鼠的肝脏脂变程度减轻,肝组织中ALT和AST活性、MDA含量及HMGCR、SCD-1和PPAR-γ的mRNA表达显著降低(P<0.05),SOD和GSH-Px活性上升(P<0.05),且黑茶高、中剂量组预防性给药的治疗效果优于低剂量组(P<0.05)。结论:安化黑茶防治高脂饮食诱导的ApoE^-/-小鼠非酒精性脂肪肝形成的机制可能是通过抑制HMGCR、SCD-1和PPAR-γ的mRNA表达来减少脂类物质合成,同时通过抗氧化来减少氧化损伤和保护肝细胞。AIM:To explore the effects of Anhua dark tea on the prevention and treatment of non-alcoholic fatty liver induced by high-fat diet in apolipoprotein E knockout(ApoE^-/-)mice and the relevant mechanisms.METHODS:Male ApoE^-/-mice(n=50,8 weeks old)were randomly divided into model group,atorvastatin group,and high-,mediumand low-dose Anhua dark tea groups,with 10 mice in each group.In addition,10 homologous wild-type male C57 BL/6 J mice were selected as normal control group.The ApoE^-/-and wild-type mice were fed with the same amount of high-fat feed and common feed for 17 weeks,respectively,and intervened by the corresponding drugs and normal saline.At the end of the experiment,HE staining was used to observe the histopathological changes of the liver.The levels of alanine aminotransfease(ALT),aspartate aminotransfease(AST),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in the liver tissues were detected.The mRNA expression levels of hydroxymethyl glutaryl coenzyme A reductase(HMGCR),peroxisome proliferator-activated receptor-γ(PPAR-γ)and steroyl coenzyme A desaturase-1(SCD-1)were detected by RT-qPCR to observe the lipid synthesis.RESULTS:In model group,increased volume,smooth surface,tight membrane and dull edge of the liver were observed,and microscopic images with HE staining showed the formation of vacuoles with varying sizes,indicating the success of establishing the model.Compared with the model group,the degree of liver steatosis,the levels of ALT,AST and MDA,and the mRNA expression of HMGCR,SCD-1 and PPAR-γin different doses of Anhua dark tea groups were significantly decreased,while the activity of SOD and GSH-Px was increased(P<0.05).The effect of Anhua dark tea in high-and medium-dose groups was better than that in low-dose group(P<0.05).CONCLUSION:Anhua dark tea prevents high-fat diet-induced non-alcoholic fatty liver in ApoE^-/-mice.The mechanism may be related to reducing lipid synthesis by inhibition of HMGCR,SCD-1 and PPAR-γexpression,and protecting liver cells t
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