KK-Ay小鼠糖尿病肾病模型气阴两虚证的演变与评价

Evolution and evaluation of deficiency of both qi and yin syndrome in KK-Ay mice diabetic nephropathy model

目的:通过观察KK-Ay小鼠糖尿病肾病(DN)模型气阴两虚证的演变,探讨DN气阴两虚证病证结合动物模型的建立与评价方法。方法:选择KK-Ay小鼠(模型组)和C57BL/6J小鼠(对照组)各30只,分别给予高脂和普通饲料喂养,观察一般情况、体质量、疾病指标-血糖指标[空腹血糖(FBG)、糖化血红蛋白(HbA1c)]、肾脏指标[24h尿量(UV)、尿白蛋白/肌酐比(UACR)、脏器系数、肾脏组织病理形态及超微结构]和证候指标-气虚证指标[(抓力、摄食量、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)]、阴虚证指标[摄水量、促肾上腺皮质激素(ACTH)、促肾上腺皮质激素释放激素(CRH)、舌面RGB值、脉搏幅度]。结果:与同周龄对照组比较,14周龄KK-Ay小鼠一般情况较差,体质量、FBG、UV、UACR显著升高(P<0.01),肾小球系膜细胞及系膜基质增生,肾小管空泡变性,足细胞足突排列紊乱、融合明显,抓力、脉搏幅度、ATP显著下降(P<0.01),食水量显著升高(P<0.01);16周龄KK-Ay小鼠除上述指标变化外,舌面G、B值、R+G+B值显著升高(P<0.05,P<0.01),CRH显著下降(P<0.05);23周龄KK-Ay小鼠肾脏脏器系数显著降低(P<0.05),ATP、ADP、ACTH、CRH显著降低(P<0.01,P<0.05)。结论:高脂喂养KK-Ay小鼠至14周龄可构建DN气阴两虚证模型,简单方便,符合中医证候特点。

Objective:To establish and evaluate the animal model of diabetic nephropathy(DN)with deficiency of both qi and yin syndrome.Methods:A total of 30 KK-Ay mice(model group)and 30 C57BL/6J mice(control group)were selected and fed with high-fat feedstuff and common feedstuff respectively.The general condition,body weight,disease indexes-blood glucose indexes[fasting blood glucose(FBG),glycosylated hemoglobin(HbA1c)],renal indexes[24 h urine volume(UV),urinary albumin/creatinine ratio(UACR),organ coefficient,pathological morphology and ultrastructure of renal tissue)and syndrome indexes-qi deficiency syndrome indexes[grasping power,food intake,adenosine triphosphate(ATP),adenosine diphosphate(ADP),yin deficiency syndrome indexes[water intake,adrenocorticotrophic hormone(ACTH),corticotrophin releasing hormone(CRH),RGB value of tongue surface,pulse amplitude were detected.Results:Compared with the control group,the general condition of 14 weeks old KK-Ay was poor,and the body weight,FBG,UV,and UACR were increased(P<0.01),glomerular mesangial cells and mesangial matrix proliferated,renal tubular vacuoles degenerated,podocytes and podocytes arranged in disorder and fused obviously,grasping power,pulse amplitude and ATP decreased significantly(P<0.01),and water intake increased significantly(P<0.01).In 16 weeks old KK-Ay mice,the G and B values and R+G+B value of the tongue surface were increased(P<0.05,P<0.01),and CRH was decreased(P<0.05);the kidney organ coefficient of 23 weeks old KK-Ay was decreased(P<0.05),The levels of ATP,ADP,ACTH and CRH were decreased(P<0.01,P<0.05).Conclusion:KK-Ay mice fed with high-fat feedstuff to the age of 14 weeks could establish DN with deficiency of both qi and yin syndrome.