Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway

LIU Ying-chu; WANG Hong-bing; WANG Ya-xin; ZHANG Hui-cun

doi:10.16025/j.1674-1307.2023.08.007

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Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway

更新时间：2023-09-18

- Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway
- Beijing Journal of Traditional Chinese Medicine Vol. 42, Issue 8, Pages: 841-846(2023)
- 作者机构：
  
  1.北京中医药大学，北京 100029
  2.首都医科大学附属北京中医医院消化中心，北京 100010
  3.北京市中医药研究所，北京 100010
- 作者简介：
- 基金信息：
- DOI：10.16025/j.1674-1307.2023.08.007
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刘颖初，汪红兵，王雅欣，等.调肝祛脂方通过miR-34a/SIRT1/PPARα通路对非酒精性脂肪肝大鼠的保护作用研究［J］.北京中医药，2023，42（8）：841-846.

LIU Ying-chu,WANG Hong-bing,WANG Ya-xin,et al.Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):841-846.
刘颖初，汪红兵，王雅欣，等.调肝祛脂方通过miR-34a/SIRT1/PPARα通路对非酒精性脂肪肝大鼠的保护作用研究［J］.北京中医药，2023，42（8）：841-846. DOI： 10.16025/j.1674-1307.2023.08.007.

LIU Ying-chu,WANG Hong-bing,WANG Ya-xin,et al.Study on mechanism of protective effect in nonalcoholic fatty liver rats by TiaoganQuzhi Formula based on miR-34a/SIRT1/PPARα signaling pathway[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):841-846. DOI： 10.16025/j.1674-1307.2023.08.007.

摘要

目的,2,观察调肝祛脂方通过微小RNA-34a（miR-34a）/沉默调节蛋白1（SIRT1）/过氧化物酶体增殖物激活受体α（PPARα）通路对非酒精性脂肪肝（nonalcoholic fatty liver disease， NAFLD）大鼠的保护作用。,方法,2,选择SD大鼠40只，按随机数字表法分为对照组、模型组、调肝祛脂方低剂量组、调肝祛脂方高剂量组，每组10只。对照组给予正常饲料喂养，其余各组以高脂饲料建立NAFLD模型。各组成模后，调肝祛脂方低、高剂量组分别按9.045、36.18 g/kg给药，灌胃体积均为1 mL/100 g，对照组和模型组予等体积蒸馏水灌胃。各组均每日灌胃1次，连续给药8周。比较各组肝脏HE染色病理改变，血脂及肝功能指标，RT-PCR法检测肝组织miR-34a、SIRT1、PPARα基因表达。,结果,2,造模后对照组大鼠精神良好、反应灵敏、一般状况较好，其余各组出现精神萎靡、活动减少等表现；干预后调肝祛脂方低、高剂量组大鼠一般状态均有改善。对照组肉眼观察肝脏光泽红润、无明显充血水肿，HE显示肝细胞排列规律、肝索清晰；模型组肉眼可见肝组织颜色苍白、充血水肿，HE染色显示肝细胞排列紊乱、有脂肪空泡变性；治疗后调肝祛脂方低、高剂量组大鼠肝脏肉眼及HE观察均有好转。与对照组相比，模型组总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、谷丙转氨酶（ALT）、谷草转氨酶（AST）水平均升高（,P,<,0.01），高密度脂蛋白胆固醇（HDL-C）水平降低（,P,<,0.01）；与模型组相比，调肝祛脂方低、高剂量组TC、TG、LDL-C、ALT、AST水平均降低，HDL-C水平高，其中调肝祛脂方高剂量组上述指标与模型组比较，差异有统计学意义（,P,<,0.05）。与对照组相比，模型组miR-34a表达高（,P,<,0.05），SIRT1、PPARα基因表达低（,P,<,0.05）；与模型组相比，调肝祛脂方低、高剂量组miR-34a表达低，SIRT1、PPARα基因表达高，且调肝祛脂方高剂量组上述指标与模型组比较差异有统计学意义（,P<,0.05）。,结论,2,调肝祛脂方可通过降低miR-34a表达，提高SIRT1/PPARα表达，调节血脂及肝功，改善NAFLD大鼠肝细胞变性。

Abstract

Objective,2,To explore the protective effect of TiaoganQuzhi Formula（regulatingliver andreducing fat） on nonalcoholic fatty liver （NAFLD） by microRNA-34a （miR-34a） /silent mating type information regulation 2 homolog-1（SIRT1）/peroxisome proliferator-activated receptor （PPARα） signaling pathway.,Methods,2,Forty SD rats were selected and randomly divided into a control group， a model group， a low-dose TiaoganQuzhi group， and a high-dose TiaoganQuzhi group， with ten rats in each group. The control group was fed with normal feed， while other groups were fed with high-fat feed to establish a nonalcoholic fatty liver model. The low and high dose TiaoganQuzhi groups were given 9.045 g/kg and 36.18 g/kg drugs respectively after modeling， with the volume of 1 mL/100 g， and the normal group and model group were given same volume of distilled water. Rats were gavaged once a day for 8 weeks. The pathological changes of liver hematoxylin-eosin（HE）， blood lipids and liver function indicators in each group were compared， and miR-34a， SIRT1 and PPARα gene expression in liver tissueweredetected by reverse transcription-polymerase chain reaction （RT-PCR） method.,Results,2,After modeling， the control group showed good mental health， sensitive response and generally good condition. Other groups showed symptoms such as mental exhaustion and decreased activity. After intervention， the general state of treatment group rats were improved. Liver of the control group was shiny and ruddy， without obvious congestion or edema by visual observation. HE showed regular arrangement of liver cells， and liver cord was clear. The model group showed liver tissue pale with congestion and edema in visible， and liver HE showed disordered arrangement of liver cells with fatty vacuolar degeneration. The treatment group showed improvement in liver observation. Compared with the control group， the model group had higher levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）（,P,<,0.01）， while lower levels of high-density lipoprotein cholesterol （HDL-C）（,P,<,0.01）. Compared with the model group， the levels of TC， TG， LDL-C in each TiaoganQuzhi dose group of were low， and the levels of HDL-C were high. The above indicators in TiaoganQuzhi high-dose group of were statistically significant compared with the model group （,P,<,0.05）. Compared with the control group， the levels of alanine transaminase （ALT）and aspartate transaminase （AST） in model group were higher （,P,<,0.01）. Compared with the model group， the levels of ALT and AST in each TiaoganQuzhi dose group were lower， and the above indicators in the TiaoganQuzhi high-dose group had statistical significance compared with the model group （,P,<,0.05）. Compared with the control group， the model group showed higher expression of miR-34a （,P,<,0.05） and lower expression of SIRT1 and PPARα genes （,P,<,0.05）. Compared with the model group， the expression of miR-34a was lower in each TiaoganQuzhi dose group， while the expression of SIRT1 and PPARα genes was higher. Moreover， there was a statistically significant difference in the above indicators between the TiaoganQuzhi high-dose group and the model group （,P,<,0.05）.,Conclusion,2,TiaoganQuzhi Formula can reduce miR-34a expression， increase SIRT1/PPARα expression， regulate blood lipids and liver function， and improve liver cell degeneration in NAFLD rats.

关键词

非酒精性脂肪肝调肝祛脂方微小RNA-34a沉默调节蛋白1过氧化物酶体增殖物激活受体α大鼠

Keywords

Nonalcoholic fatty liverTiaoganQuzhi FormulamicroRNA-34asilencing regulatory protein 1peroxisome proliferator-activated receptorrats

references

FRIEDMAN SL, NEUSCHWANDER-TETRI BA, RINELLA M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018,24(7):908-922.

MERRY TL, TRAN M, DODD GT, et al. Hepatocyte glutathione peroxidase-1 deficiency improves hepatic glucose metabolism and decreases steatohepatitis in mice[J]. Diabetologia, 2016,59:2632-2644.

GORI M, ARCIELLO M, BALSANO C. Micrornas in nonalcoholic fatty liver disease: novel biomarkers and prognostic tools during the transition from steatosis to hepatocarcinoma[J]. Biomed Res Int, 2014,2014:741465.

WANG L, SUN M, CAO Y, et al. miR-34a regulates lipid metabolism by targeting sirt1 in non-alcoholic fatty liver disease with iron overload[J]. Arch Biochem Biophys, 2020,695:108642.

段晓燕, 范建高. 2010国家级脂肪性肝病诊疗进展研讨会纪要[J]. 胃肠病学和肝病学杂志,2010,19(6):566-568.

BUZZETTI E, PINZANI M, TSOCHATZIS EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)[J]. Metabolism, 2016,65(8):1038-1048.

SUKSANGRAT T, PHANNASIL P, JITRAPAKDEE S. miRNA regulation of glucose and lipid metabolism in relation to diabetes and non-alcoholic fatty liver disease[J]. Adv Exp Med Biol, 2019,1134:129-148.

MOTA M, BANINI BA, CAZANAVE SC, et al. Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease[J]. Metabolism, 2016,65(8):1049-1061.

NASSIR F, IBDAH JA. Sirtuins and nonalcoholic fatty liver disease[J]. World J Gastroenterol, 2016,22(46):10084-10092.

HAN X, WU Y, YANG Q, et al. Peroxisome proliferator-activated receptors in the pathogenesis and therapies of liver fibrosis[J]. Pharmacol Ther, 2021,222:107791.

MONTAGNER A, POLIZZI A, FOUCHÉ E, et al. Liver pparΑ is crucial for whole-body fatty acid homeostasis and is protective against nafld[J]. Gut, 2016,65(7):1202-1214.

NIKAM A, PATANKAR J V, SOMLAPURA M, et al. The pparΑ agonist fenofibrate prevents formation of protein aggregates (mallory-denk bodies) in a murine model of steatohepatitis-like hepatotoxicity[J]. Sci Rep, 2018,8(1):12964.

XU Y, ZHU Y, HU S, et al. Hepatocyte mir-34a is a key regulator in the development and progression of non-alcoholic fatty liver disease[J]. Mol Metab, 2021,51:101244.

WANG L, SUN M, CAO Y, et al. miR-34a regulates lipid metabolism by targeting sirt1 in non-alcoholic fatty liver disease with iron overload[J]. Arch Biochem Biophys, 2020,695:108642.

GUO XY, SUN F, CHEN JN, et al. CIRCRNA_0046366 inhibits hepatocellular steatosis by normalization of ppar signaling[J]. World J Gastroenterol, 2018,24(3):323-337.

覃映霖, 胡振斌, 陈彩凤,等. 非酒精性脂肪肝证候分布规律探析[J]. 中国中医药现代远程教育,2021,19(17):45-48.

张巍, 邵明亮, 苗同国,等. 清热利湿方对脂肪肝细胞磷脂肌醇-3激酶/肾上腺受体激酶表达的调节作用研究[J]. 北京中医药,2020,39(8):832-836,封3.

穆杰, 王庆国, 王雪茜,等. 论肝郁生痰为非酒精性脂肪肝病机[J]. 环球中医药,2017,10(1):34-36.

刘福栋, 庞博, 吕文良,等. 从气虚络瘀角度探讨肝纤维化氧化应激机制[J]. 北京中医药,2022,41(6):634-636.

石雪娅. 非酒精性肥胖型脂肪肝的中医药研究现状及展望[J]. 中医临床研究,2018,10(24):54-57.

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