湖南中医药大学学报2023,Vol.43Issue(12):2171-2176,6.DOI:10.3969/j.issn.1674-070X.2023.12.005
左归降糖清肝方对糖尿病性脂肪肝小鼠PGC-1α和DNMT3A表达的影响
Effects of Zuogui Jiangtang Qinggan Formula on PGC-1α and DNMT3A expressions of liver in diabetic fatty liver mice
摘要
Abstract
Objective To investigate the effects of Zuogui Jiangtang Qinggan Formula(ZGJTQGF)on the expression of peroxisome proliferation-activated receptor-γ-coactivator 1α(PGC-1α)and DNA methyltransferase 3A(DNMT3A)in fatty liver development of transgenic MKR mice with type 2 diabetes mellitus following a high-fat diet.Methods A total of 24 MKR mice were randomly divided into control group,high fat model group and ZGJTQGF group.High fat model group and ZGJTQGF group were fed with high fat diet for eight weeks,and control group was fed with basic diet.After feeding high-fat diet for four weeks,the Chinese medicine group was treated with Chinese medicine decoction for four weeks,and the other groups were given the same amount of distilled water.Fasting blood glucose was determined by electrochemical method.The content of triglyceride(TG)and free fatty acid(FFA)in liver tissue was determined by the kit.HE staining was used to observe the morphological structure and pathological changes of liver tissue.The mRNA expressions of PGC-1α,mitochondrial transcription factor A(TFAM),nuclear respiratory factor-1(NRF1),and DNMT3A in mice liver were tested by qRT-PCR,and the protein expressions of PGC-1α and DNMT3A were checked by Western blot and immunohistochemical analysis.Results High-fat diet induced the formation of nonalcoholic fatty liver in MKR mice.The liver cells had fat droplets of different sizes,which showed fatty changes.Compared with the control group,the blood glucose,liver index,TG and FFA content of liver tissue in the high-fat model group significantly increased(P<0.01),the PGC-1α,NRF1,and protein expression of mRNA and PGC-1α significantly decreased(P<0.01;the mRNA and protein expressions of DNMT3A significantly increased(P<0.01).Compared with high-fat model group,ZGJTQGF group had lower blood glucose,liver index,and TG and FFA content in liver tissues of high-fat diet MKR mice(P<0.01),up-regulated mRNA expressions of PGC-1α,NRF1,and TFAM in liver and the PGC-1α protein expression(P<0.01),down-regulated mRNA and protein expressions of DNMT3A(P<0.01).Conclusion ZGJTQGF alleviates hepatic steatosis by regulating the expression of PGC-1α and its pathway related genes,which may be mediated by inhibiting the expression of DNMT3A and reducing the correlation of PGC-1α DNA methylation.关键词
左归降糖清肝方/糖尿病性脂肪肝/PGC-1α/DNMT3A/甲基化Key words
Zuogui Jiangtang Qinggan Formula/diabetic fatty liver/peroxisome proliferation-activated receptor-γ-coacti-vator 1α/DNA methyltransferase 3A/Methylation分类
医药卫生引用本文复制引用
彭泉,钟雁城,杨霄旭,成细华..左归降糖清肝方对糖尿病性脂肪肝小鼠PGC-1α和DNMT3A表达的影响[J].湖南中医药大学学报,2023,43(12):2171-2176,6.基金项目
国家自然科学基金区域联合创新研究重点支持项目(U21A20411) (U21A20411)
湖南省自然科学基金项目(2021JJ30491) (2021JJ30491)
湖南省教育厅重点项目(20A376) (20A376)
湖南省卫健委重点项目(A202303066904) (A202303066904)
湖南省教育厅一般项目(19C1385) (19C1385)
湖南中医药大学大学生创新创业训练计划(2021-128,2022-153) (2021-128,2022-153)
湖南中医药大学一流学科《基础医学》项目 ()
湖南省国内一流培育学科中西医结合学科项目 ()
中西医结合病原生物学湖南省重点学科. ()