论文部分内容阅读
目的:筛选并初步建立能够诱导小鼠肝肾同时损伤的实验动物模型,为评价肝肾损伤治疗药物提供实验动物模型。方法:考察尾静脉注射刀豆蛋白A(Con A)10,15,20,40 mg·kg-1,造模时间12 h;ig给药D-半乳糖胺(D-Gal)1 g·kg-1及腹腔注射0.3%四氯化碳(CCl4,20 mL·kg-1)60 mg·kg-1,造模时间24 h;药物对模型小鼠肝脏、肾脏的损伤作用,通过检测肝肾功能相关的生化指标,肝脏及肾脏病理组织学改变,确定有效的造模方案。为进一步确定该模型是否能有效评价治疗肝肾损伤药物的药效,考察了大黄甘草汤对小鼠肝肾损伤模型的保护作用。结果:给予小鼠1 g·kg-1D-Gal,CCl460 mL·kg-1造模后,其血清直接胆红素(DBIL)、总胆红素(TBIL)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性与对照组比较均显著升高(P<0.05或P<0.01),而尿素氮(BUN)、肌酐(CRE)、总胆固醇(TC)、甘油三脂(TG),血清总蛋白(TP)、白蛋白(ALB)含量无明显变化,组织病理变化与血清生化指标结果相同,说明上述两种药物可诱发小鼠肝损伤模型,但未检测到肾损伤相关生化指标及病理变化;给予小鼠Con A 20 mg·kg-1造模后,小鼠血清DBIL,TBIL,ALT,AST,BUN,TC,TG,CRE,TP,ALB值与对照组相比较差异显著(P<0.01,P<0.05),说明Con A 20 mg·kg-1可诱发小鼠肝肾同时损伤,进一步优化模型,确定15 mg·kg-1Con A为诱发小鼠肝肾损伤的最佳剂量;给予模型验证方药大黄甘草汤干预后,肝肾损伤小鼠的生化和组织学检查均有显著改善。结论:初步建立尾静脉注射Con A 15 mg·kg-1诱导小鼠实验性肝肾同时损伤模型,用大黄甘草汤验证说明模型建立成功。
OBJECTIVE: To screen and preliminarily establish an experimental animal model capable of inducing simultaneous liver and kidney injury in mice and provide experimental animal models for the evaluation of drugs for liver and kidney injury. Methods: The caudal vein was injected with Con A 10,15,20,40 mg · kg-1 for 12 h, and D-galactosamine 1 g · kg 1 and intraperitoneal injection of 0.3% carbon tetrachloride (CCl4, 20 mL · kg-1) 60 mg · kg-1, the model time was 24 h. The effects of drugs on the liver and kidney in mice were detected by detecting liver and kidney Function-related biochemical indicators, liver and kidney histopathological changes to determine an effective modeling program. To further determine whether the model can effectively evaluate the efficacy of drugs for treating liver and kidney injury, the protective effect of rhubarb and licorice soup on liver and kidney injury in mice was investigated. RESULTS: After administration of 1 g · kg-1 D-Gal and 60 μg · kg-1 of CCl4, the levels of serum direct bilirubin (DBIL), total bilirubin (TBIL), alanine aminotransferase Aspartate aminotransferase (AST) activity was significantly higher than that of the control group (P <0.05 or P <0.01), while the levels of BUN, CRE, TC, TG ), Serum total protein (TP), albumin (ALB) content had no significant change, histopathological changes and serum biochemical indicators of the same, indicating that the two drugs can induce liver injury in mice model, but did not detect the renal injury related biochemistry Index and histopathological changes. The levels of DBIL, TBIL, ALT, AST, BUN, TC, TG, CRE, TP and ALB in serum of mice after 20 mg · kg-1 Con A treatment were significantly different from those of the control group (P <0.01, P <0.05), indicating that con A 20 mg · kg-1 can induce simultaneous liver and kidney injury in mice, and further optimize the model to determine 15 mg · kg-1Con A induced liver and kidney damage in mice the best Dose; given the model validation rhubarb liquorice soup intervention, liver and kidney injury in mice biochemical and histological examination were significantly improved. CONCLUSION: The model of simultaneous liver and kidney injury induced by Con A at the dose of 15 mg · kg-1 in tail vein is established. The model of Rhizoma Glycyrrhizae is validated.