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目的探讨血红素加氧酶-1(HO-1)对肝硬化导致的糖代谢紊乱的影响及机制。方法 50只雄性SD大鼠随机分4组:假手术组、肝硬化组、锌原卟啉-IX(ZnPP-IX)组、氯高铁血红素(Hemin)组。除假手术组外,其余3组造肝硬化模型,于造模成功后,向ZnPP-IX组大鼠隔日一次(qod)腹腔注射ZnPP-IX 10μmol/kg,Hemin组大鼠同时点腹腔注射Hemin 30μmol/kg,肝硬化组和假手术组大鼠同时点腹腔注射等量生理盐水,共干预4周。于4周末做葡萄糖耐量实验,测各组糖代谢相关指标。采用免疫组化和Western blot检测HO-1蛋白在肝组织中的表达情况。结果肝硬化组大鼠肝组织HO-1蛋白表达高于假手术组和ZnPP-IX组(P<0.05),低于Hemin组(P<0.05)。各组间空腹血糖(FPG)差异无统计学意义(P>0.05)。与假手术组比,肝硬化组大鼠2h血糖(PPG)、空腹胰岛素(FINS)、2h胰岛素(PINS)、胰岛素抵抗指数(HOMA-IR)均增高(P均<0.05),胰岛素敏感指数(ISI)则降低(P<0.05)。ZnPP-IX组较肝硬化组PPG、FINS、PINS、HOMA-IR进一步增高(P均<0.05),ISI进一步降低(P<0.05)。Hemin组相比肝硬化组各指标变化与ZnPP-IX组相反(P均<0.05)。结论提高HO-1在肝脏的表达能改善肝硬化大鼠的糖代谢紊乱,其作用机制可能与HO-1代谢产物所具备的保护作用有关。
Objective To investigate the effect and mechanism of heme oxygenase-1 (HO-1) on disturbance of glucose metabolism caused by cirrhosis. Methods Fifty male Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, cirrhosis group, ZnPP-IX group and Hemin group. Except for the sham-operation group, the other three groups were made into the model of cirrhosis. After the model was established successfully, ZnPP-IX 10μmol / kg was intraperitoneally injected into the ZnPP-IX group, and the Hemin group was given intraperitoneal injection of Hemin At 30μmol / kg, rats in cirrhosis group and sham operation group were injected intraperitoneally with the same amount of normal saline for 4 weeks. Glucose tolerance test was done at the end of 4 weeks, and the indexes of glucose metabolism in each group were measured. The expression of HO-1 protein in liver tissue was detected by immunohistochemistry and Western blot. Results The expression of HO-1 protein in liver cirrhosis group was higher than that in sham operation group and ZnPP-IX group (P <0.05), but lower than that in Hemin group (P <0.05). There was no significant difference in fasting plasma glucose (FPG) among the three groups (P> 0.05). Compared with sham operation group, the levels of blood glucose (PPG), fasting insulin (FINS), 2h insulin (PINS) and insulin resistance index (HOMA-IR) in liver cirrhosis group were significantly increased (P <0.05) ISI) decreased (P <0.05). The levels of PPG, FINS, PINS and HOMA-IR in ZnPP-IX group were significantly higher than those in cirrhosis group (all P <0.05), and the ISI was further decreased (P <0.05). Hemin group compared with the changes of various indicators of liver cirrhosis and ZnPP-IX group opposite (P all <0.05). Conclusions Increasing the expression of HO-1 in the liver can improve the disorder of glucose metabolism in cirrhotic rats. The mechanism may be related to the protective effect of HO-1 metabolites.