阿霉素肾病大鼠模型的优化

Optimization of adriamycin-induced nephropathy rat model

目的确定适合于防己黄芪汤药效评价的阿霉素肾病大鼠模型最佳造模方法。方法通过改变阿霉素给药剂量和给药次数,并给予防己黄芪汤系列受试药物进行干预,以大鼠体质量、脏器指数、尿蛋白定量、肾组织病理以及血清生化指标等为评价指标,探索不同的阿霉素给药剂量和次数对模型的影响。结果 M1[(5+2)mg/kg]模型,大鼠死亡率较高;M2(6 mg/kg)模型,死亡率高达20%,给予供试药物干预,反映肾功能的各项指标不仅没有回调,反而沿模型组变化方向表现更高的水平;对于M3[(4+2)mg/kg]模型,大鼠部分指标:肺脏和肾脏脏器指数、血清三酰甘油(TG)及总蛋白(TP)水平发生回调,但治愈效果并不理想;对于M4或M4’[(4+1)mg/kg]模型,于造模第14天,大鼠尿蛋白定量水平与对照组相比,具有显著性差异,且呈现持续稳定增长趋势,给予防己黄芪汤高、中、低剂量,各指标均有不同程度回调。结论最终确定采用大鼠起始造模体质量约300 g,阿霉素造模累计剂量为5 mg/kg,分2次尾iv给药,首次于实验第1天注射4mg/kg,时隔1周,于实验第8天注射1 mg/kg,为最佳造模方式,适合评价由防己黄芪汤衍生的相关受试药物的药效作用。

Objective To determine the optimal model for the evaluation of pharmacodynamics of Fangji Huangqi Decoction. MethodsBy changing the doses and times of doxorubicin and the intervention of Fangji Huangqi Decoction and a series of test drugs, the effects of different doses and times of doxorubicin on the model were explored, and body weight, organism index, urine protein quantitation, renal histopathology results, and serum biochemistry can be regarded as evaluation indexes. Results For M1（5 ＋ 2） mg/kg model, the mortality rate of rats was higher. For M2（6 mg/kg） model, the mortality rate was up to 20%, and the indicators reflecting renal function did not callback, but instead it showed much higher levels than the model group after receiving the test drug. For M3（4 ＋ 2） mg/kg model, the callback of part of the indexes, such as lung and kidney organ index, serum total triglyceride, and total protein levels, occurred after receiving the test drug, but the curative effect is not ideal. For M4 or M4＇（4 ＋ 1） mg/kg model, the quantitative level of urinary protein in model rats was significantly different from that in the control at the 14 th d, and the sustained and stable growth trend was observed; Moreover, the indicators mentioned above have different degrees of callback with high-, middle-, and low dose of Fangji Huangqi Decoction. Conclusion The final model weight of the rats was determined to be about 300 g, and the cumulative dose of doxorubicin was 5 mg/kg tail intravenous injection of doxorubicin was adopted as follows： on the 1 st d of the experiment, 4 mg/kg doxorubicin was injected, and followed another 1 mg/kg at intervals of 1 week, which was the best way to evaluate the pharmacological effect of the related drugs derived from the Fangji Huangqi Decoction and the middle dose was the best.