2型糖尿病合并肝纤维化大鼠模型构建的初探
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1.福建医科大学实验动物中心;2.福建医科大学孟超肝胆医院

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福建省自然科学基金面上项目(2020J011152)


Establishment and evaluation of rat model of type 2 diabetes with liver fibrosis
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1.Laboratory Animal Center,Fujian Medical University;2.Mengchao Hepatobiliary Hospital of Fujian Medical University

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Funded by the Natural Science Foundation of Fujian (2020J011152)

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    摘要:

    目的 采用高脂高糖膳食联合CCl4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%四氯化碳(CCl4, 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% CCl4、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(FBG)含量。酶联免疫吸附分析 (ELISA)检测血液中胰岛素(INS)与糖化血红蛋白(HbA1c)含量。血清生化分析检测谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(Tbil)、透明质酸(HA)水平。肝组织匀浆、生化分析羟脯氨酸(HYP)含量。HE染色、Masson染色检查肝组织形态改变。 结果 与正常对照组与肝纤维化组比较,糖尿病合并肝纤维化组大鼠FBG、HbA1c含量,胰岛素抵抗指数(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、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。 结论 高脂高糖膳食联合CCl4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。

    Abstract:

    Objective To establish a rat model of type 2 diabetes mellitus with hepatic fibrosis by using the high-lipid-sugar diet (HLSD) combined with the inducement of CCl4 and streptozotocin. Methods SD rats were randomly divided into liver fibrosis (LF) group, type 2 diabetes combined with liver fibrosis (DLF) group, and normal group, 10 rats in each group. All rats in LF or DLE group were fed with HLSD for 4 weeks, and then all rats were intraperitoneally injected 20% carbon tetrachloride (CCl4, once in a week) according to the body weight of 5 mL/kg to induce hepatic fibrosis for another 4 weeks. During the CCl4 treatment, rats in the DLF group were also intraperitoneally injected with 25 mg/kg streptozotocin (STZ, once in a week). After STZ treatment, the content of FBG, INS, HOMA-IR, and HbA1c were evaluated once in a week. The FBG level was detected by blood glucose meter. The contents of INS and HbA1c were detected by ELISA method. 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 staining and Masson staining were used to evaluate the pathological changes in liver tissues. Results The contents of FBG, HbA1c and HOMA-IR in DLF group were significantly increased as compared to those in normal or LF group. While the INS content in DLF group was significantly decreased when compared to those in normal or LF group. Comparing with normal group, the high levels of ALT, AST, Tbil, HA and HYP, as well as fibrotic changes and inflammation in liver tissue were all observed in LF group and DLF group. Conclusions HLSD combined with CCl4 and streptozotocin inducement is an effective strategy to establish a rat model of type 2 diabetes mellitus with liver fibrosis.

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  • 收稿日期:2024-05-30
  • 最后修改日期:2024-11-29
  • 录用日期:2024-12-23
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