2型糖尿病合并肝纤维化大鼠模型构建的初探  

Establishment and evaluation of rat model of type 2 diabetes with liver fibrosis

作　　者：何宏星 廖乃顺 HE Hongxing;LIAO Naishun(Laboratory Animal Center,Fujian Medical University,Fuzhou 350004,China;the United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350028,China)

机构地区：[1]福建医科大学实验动物中心,福州350004 [2]福建医科大学孟超肝胆医院,福建省孟超肝胆技术联合创新重点实验室,福州350028

出　　处：《中国实验动物学报》2025年第1期82-88,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：福建省自然科学基金项目(2020J011152)。

摘　　要：目的采用高脂高糖膳食联合四氯化碳(carbon tetrachloride,CCl_(4))与链脲佐菌素诱导法构建2型糖尿病合并肝纤维化动物模型。方法SD大鼠按体质量随机分为肝纤维化组、糖尿病合并肝纤维化组及正常对照组,每组10只。肝纤维化组、糖尿病合并肝纤维化组大鼠饲喂高脂高糖饲料4周后,肝纤维化组按体质量5 mL/kg腹腔注射20%CCl_(4)(1次/周),诱导肝纤维化模型,糖尿病合并肝纤维化组大鼠分别按体质量5 mL/kg腹腔注射20%CCl_(4)、25 mg/kg链脲佐菌素(1次/周),两组动物继续高脂高糖喂养4周。尾静脉取血检测空腹血糖(fasting blood glucose,FBG)含量。酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测血液中胰岛素(insulin,INS)与糖化血红蛋白(hemoglobin A1c,HbA1c)含量。血清生化分析检测谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、总胆红素(total bilirubin,Tbil)、透明质酸(hyaluronic acid,HA)水平。肝组织匀浆、生化分析羟脯氨酸(hydroxyproline,HYP)含量。苏木素-伊红(HE)染色、Masson染色检查肝组织形态改变。结果与正常对照组和肝纤维化组比较,糖尿病合并肝纤维化组大鼠FBG、HbA1c含量和胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)显著升高,INS含量显著减少。与正常对照组比较,肝纤维化组、糖尿病合并肝纤维化组血清的ALT、AST、Tbil和HA水平,肝组织的HYP含量显著增加,且呈炎症细胞浸润、纤维化增生病变,肝组织炎症分级在G1级、G2级,纤维化分期主要在S2期。结论高脂高糖膳食联合CCl_(4)与链脲佐菌素诱导法可构建2型糖尿病合并肝纤维化大鼠模型。Objective To establish a rat model of type 2 diabetes mellitus with hepatic fibrosis using a high-lipid-sugar diet(HLSD)combined with inducement with carbon tetrachloride(CCl_(4))and streptozotocin.Methods SD rats were randomly divided into a liver fibrosis(LF)group,type 2 diabetes combined with liver fibrosis(DLF)group,and normal group,with 10 rats in each group.All rats in the LF or DLE group were fed an HLSD for 4 weeks;then,all rats were intraperitoneally injected with 20%CCl_(4)(once a week)according to body weight(5 mL/kg)to induce hepatic fibrosis for another 4 weeks.During CCl_(4)treatment,rats in the DLF group were also intraperitoneally injected with 25 mg/kg STZ(once a week).After STZ treatment,the contents of FBG,INS,HOMA-IR,and HbA1c were evaluated once a week.The level of FBG was detected by blood glucose meter,and INS and HbA1c contents were detected by ELISA.Biochemical analysis was used to analyze the serum levels of AST,ALT,Tbil,and HA,as well as the HYP content in liver tissues.HE and Masson staining were used to evaluate pathological changes in liver tissues.Results The contents of FBG,HbA1c,and HOMA-IR were significantly increased,while the INS content was significantly decreased in the DLF group compared with those in the normal or LF group.Compared with the normal group,the LF group and DLF group showed higher levels of ALT,AST,Tbil,HA,and HYP,as well as fibrotic changes and inflammation in the liver tissue.Conclusions HLSD combined with CCl_(4)and STZ inducement is an effective strategy for establishing a rat model of type 2 diabetes mellitus with liver fibrosis.

关 键 词：2型糖尿病 肝纤维化 糖尿病合并肝纤维化 大鼠 

分 类 号：Q95-33[生物学—动物学]