目的建立高血糖大鼠肝损伤模型,探讨胰岛素强化治疗的疗效。方法利用链脲佐菌素(STZ)和D-半乳糖胺(D-gal)注射建立高血糖肝损伤模型大鼠,分为强化治疗组(血糖控制在6~8mmol/L)和常规治疗组(血糖控制在9-12mmol/L),分别于损伤模型制备前及制备后1、3、5、7d处死大鼠,经腹主动脉抽血检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(T-Bil)、白蛋白(ALB)、总蛋白(TP)、碱性磷酸酶(ALP)含量。取上述处死的大鼠肝脏组织,制作病理切片,行HE染色观察。取第7天大鼠肝组织行组织电镜观察。结果成功建立了大鼠高血糖肝损伤模型。胰岛素强化治疗可明显降低模型大鼠的死亡风险,强化治疗组病死率明显低于常规治疗组(P〈O.01);胰岛素强化治疗后,肝脏ALT、AST、T-Bil明显降低,ALB、TP升高,ALP降低(P〈0.05或P〈0.01);HE染色及透射电镜结果表明肝细胞变性坏死显著减少。结论胰岛素强化治疗可降低高血糖肝损伤大鼠的病死率,减轻肝脏损伤程度,具有很好的临床应用前景。
Objective To reproduce a liver injury model in hyperglycemic rats, and investigate the effect of intensive insulin therapy on the liver. Methods Streptozotocin (STZ) and D-gal were injected to reproduce hyperglycemic liver injury model in rats. These rats were divided into intensive insulin group (with blood glucose controlled at 6-8mmol/L) and conventional treatment group (with blood glucose 9-12mmol/L). Before and 1, 3, 5, 7 days after the reproduction of the model, the rats were sacrificed, and alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, total protein, alkaline phosphatase were determined. The pathological sections of the liver tissues from the model rats and normal rats were made, they were examined after HE staining. Electron microscopic examination was also performed for the liver tissue of the 7-d models. Results Liver injury model of rats with hyperglycemia was successfully reproduced. Intensive insulin therapy can reduce the death risk in model rats. The mortality of rats was lower in intensive insulin group than in conventional treatment group (P〈0.01). After intensive insulin therapy, ALT, AST, T-Bil and ALP decreased, while albumin and total protein increased (P〈0.01 or P〈0.05). HE staining and transmission electron microscopy revealed that degeneration and necrosis of hepatocytes were ameliorated. Conclusion The liver injury model of rats with hyperglycemia has been successfully reproduced. Intensive insulin therapy can decrease the mortality of model rats and reduce the degree of rat liver injury, and the results show a prospect for clinical application.