摘要
目的探讨hsa_circ_0004535对2型糖尿病(T2DM)合并代谢相关脂肪性肝病(MAFLD)模型小鼠的影响。方法选取48只SPF级健康Balb/c小鼠进行建模并分组,每组6只,对照组:正常饲料喂养;T2DM组:2型糖尿病高糖高脂饲料诱导的糖尿病模型;T2DM合并MAFLD组:非酒精性脂肪肝高糖高脂饲料诱导糖尿病合并脂肪肝模型;T2DM合并MAFLD+hsa_circ_NC组:建模4周后,尾静脉注射每只10 nmol hsa_circ_NC;T2DM合并MAFLD+hsa_circ_0004535组:建模4周后,尾静脉注射每只10 nmol circ_0004535;T2DM合并MAFLD+miRNA_NC组:建模4周后,尾静脉注射每只10 nmol miRNA空白对照;T2DM合并MAFLD+miR-1827 agomir组:建模4周后,尾静脉注射每只10 nmol miR-1827 agomir;T2DM合并MAFLD+miR-1827 antagomir组:建模4周后,尾静脉注射每只10 nmol miR-1827 antagomir。给予干预措施后每周测量体质量并记录;进行葡萄糖耐量和胰岛素耐受实验;测血脂、肝功能;计算肝指数、胰岛素抵抗指数;病理学指标(HE染色、油红O染色、免疫组化、TUNEL染色、Masson染色)检测肝炎症、脂肪沉积及纤维化程度。结果(1)注射hsa_circ_0004535组的动物体质量、肝重量、肝指数、胰岛素抵抗指数及生化指标均显著低于注射hsa_circ_NC组与T2DM合并MAFLD组(P<0.05)。(2)HE染色显示,T2DM合并MAFLD+circ_0004535组,脂肪变性空泡减少变小,炎性细胞浸润减少。油红O染色结果和HE染色结果相一致。(3)TUNEL染色显示,T2DM合并MAFLD+hsa_circ_0004535组TUNEL阳性细胞明显减少(P<0.05)。(4)Masson染色显示,T2DM合并MAFLD+hsa_circ_0004535组胶原纤维沉积显著减少(P<0.05)。结论在T2DM合并MAFLD的动物模型中,hsa_circ_0004535和miRNA-1827的表达在调控脂质代谢、胰岛素敏感性、炎症通路、肝细胞凋亡、肝纤维化相关通路方面发挥着重要作用。
Objective To explore the influence of hsa_circ_0004535 on type 2 diabetes(T2DM)combined with metabolic-associated fatty liver disease(MAFLD)model mice.MethodsForty-eight healthy SPF grade Balb/c mice were selected for modeling and divided into the following groups(n=6 per group):Control group:normal feed;T2DM group:diabetes model induced by high-glucose and high-fat diet;T2DM combined MAFLD group:non-alcoholic fatty liver high-glucose and high-fat diet-induced diabetes combined with fatty liver model;T2DM combined MAFLD+hsa_circ_NC group:after 4 weeks of modeling,10 nmol hsa_circ_NC injected into the tail vein;T2DM combined MAFLD+hsa_circ_0004535 group:after 4 weeks of modeling,10 nmol circ_0004535 injected into the tail vein;T2DM combined MAFLD+miRNA_NC group:after 4 weeks of modeling,10 nmol miRNA blank control injected into the tail vein;T2DM combined MAFLD+miR-1827 agomir group:after 4 weeks of modeling,10 nmol miR-1827 agomir injected into the tail vein;and T2DM combined MAFLD+miR-1827 antagomir group:after 4 weeks of modeling,10 nmol miR-1827 antagomir injected into the tail vein.Mouse body weight was measured after the interventions and recorded weekly.Glucose and insulin tolerance tests were performed,blood lipids and liver function were measured,the liver and insulin resistance indexes were calculated,and pathological tests(hematoxylin/eosin(HE),oil red O,and Masson staining,immunohistochemistry,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL))were performed to measure the degree of hepatic inflammation,fat deposition,and fibrosis.Results(1)Body weight,liver weight,liver index,insulin resistance index,and biochemical indexes were all significantly lower in the hsa_circ_0004535 injection group compared with the hsa_circ_NC injection group and the T2DM combined MAFLD group(both P<0.05).(2)Steatosis vacuoles were reduced and smaller and inflammatory cell infiltration was reduced in the T2DM combined MAFLD+circ_0004535 group,as shown by HE and oil red staining.(3)TUNEL-positive cells were significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group(P<0.05).(4)Collagen fiber deposition was significantly reduced in the T2DM combined MAFLD+hsa_circ_0004535 group,as shown by Masson staining(P<0.05).ConclusionsThe expression of hsa_circ_0004535 and miRNA-1827 play important roles in regulating lipid metabolism,insulin sensitivity,inflammatory pathways,hepatocyte apoptosis,and hepatic fibrosis-related pathways in an animal model of T2DM combined with MAFLD.
作者
周彩娟
李敏
徐卉
陈兵茹
孟清
熊玮
ZHOU Caijuan;LI Min;XU Hui;CHEN Bingru;MENG Qing;XIONG Wei(the Sixth Affiliated Hospital of Xinjiang Medical University,Urumqi 830063,China;Xinjiang Production and Construction Corps Hospital,Urumqi 830092)
出处
《中国比较医学杂志》
2025年第8期78-93,共16页
Chinese Journal of Comparative Medicine
基金
新疆医科大学第六附属医院科研专项基金-在读博士生专项基金(LFYKYZX2023-16)。
作者简介
周彩娟(1993-),女,在读硕士研究生,研究方向:内分泌与代谢病临床医疗技能训练。E-mail:1748104787@qq.com;通信作者:李敏(1977-),女,博士,硕士生导师,研究方向:糖尿病及其并发症。E-mail:limin_77711@163.com。
