阿霉素诱发肾性水肿病症大鼠模型的建立

Establishment of rat models of adriamycin-induced renal edema based on disease combined with TCM syndrome type

目的考察复制大鼠的肾性水肿(肾阴虚、肾阳虚水肿)病症结合模型的可行性。方法采用灌胃甲状腺素片及尾静脉注射阿霉素的方法制造大鼠肾阴虚水肿模型,肌注氢化可的松和尾静脉注射阿霉素方法制造大鼠肾阳虚水肿模型。通过观察模型大鼠体征变化、24 h尿蛋白含量、三碘甲状腺原氨酸(T3)、甲状腺(T4)、环磷酸腺苷(c AMP)、环磷酸鸟苷(c GMP)、雌二醇(E2)及睾酮(T)等指标含量,判断模型是否成功。结果阴虚水肿组动物出现多动、脱毛、大便干结、体重降低和体温升高等临床表现,与空白组比较T3、T4、c AMP、E2、24h尿蛋白含量明显升高,c GMP、T含量降低,c AMP/c GMP比值显著升高,且各项指标均差异具有显著性(P<0.05)。阳虚水肿组动物则出现活动减少、大便溏泻、体重和体温下降等体征变化,与空白组相比,T3、T4、c AMP、E2含量显著降低,c GMP、T、24h尿蛋白含量明显升高,c AMP/c GMP比值降低,且各项指标均差异具有显著性(P<0.05)。结论分别由甲状腺素片联合阿霉素、氢化可的松注射液联合阿霉素诱导的动物病症结合模型,符合中医证型诊断下肾阴虚、阳虚水肿病症,造模方法可行。

Objective To study the feasibility of rat models of renal edema based on disease combined with traditional Chinese medicine syndrome yin-deficiency and yang-deficiency types. Methods Gastric gavage of thyroxine and tail vein injection of Adriamycin were performed to induce a rat model of kidney Yin deficiency edema, and intramuscular injection of hydroeortisone and tail vein injection of Adriamyein were used to establish a rat model of kidney Yang deficiency edema. The 24 h urine protein content, triiodothyronine （T3）, thyroxine （1＂4）, cyclic adenosine monophosphate （cAMP）, cyclic guanosine monophosphate （eGMP）, estradiol （E2） and testosterone （T） and other indicators were assayed to determine whether the rat models were successfully established. Result The rats of Yin deficiency edema group had clinical presentation such as hyperactivity, hair loss, dry stool, weight loss and temperature rise. Compared with the blank group, T3, T4, cAMP, E2, and 24 h urinary protein levels were significantly increased, cGMP and T content decreased, and cAMP/cGMP ratio was significantly increased, showing significant differences （P 〈 0.05 for all）. The Yang deficiency edema animals displayed reduced activity, diarrhea, decreased body weight and body temperature, and other signs of disease. Compared with the blank group, T3, T4, cAMP, and E2 contents were significantly decreased, cGMP, T, and 24 h urinary protein levels were significantly increased, and cAMP/cGMP ratio decreased, showing significant differences （P 〈 0.05 for all）. Conclusions The rat model of renal edema disease combined with TCM syndrome yin-deficiency was successfully induced by thyroxine in combination with Adriamycin, and the rat model of renal edema based on disease combined with TCM syndrome yang-deficiency is suecesslully established by administration of hydrocortisone plus Adriamycin. These two rat models demonstrate similar clinic^d manifestations of human renal edema based on disease combined with TCM syndrome yin-deficiency and yang-deficiency, respeetively, therefore, may serve as useful tools for further research on this disease.