研究肾结石草酸钙纳米晶体中动物模型的选择

Selection of Animal Models for Studying Calcium Oxalate Nanocrystals in Renal Stones

摘要: 目的：研究3种肾草酸钙结石动物模型中纳米晶体造模的优缺点。方法：将20只SD大鼠、20只C57BL/6N小鼠、20只KM小鼠分为6组。造模I组为10只SD大鼠，采用1%乙二醇 + 2%氯化铵2 ml进行灌胃，造模28天。对照I组为10只SD大鼠采用常规喂养 + 生理盐水2 ml进行灌胃，造模28天。造模II组为10只C57BL/6N小鼠，采用100 mg/kg的乙醛酸腹腔注射，造模7天。对照II组为10只C57BL/6N小鼠采用同等量生理盐水腹腔注射，造模7天。造模III组为10只KM小鼠，采用80 mg/kg的乙醛酸进行腹腔注射，造模7天。对照III组为10只KM小鼠采用同等量生理盐水腹腔注射，造模7天。电镜下观察各组尿液中纳米晶体的形态和聚集，比较I组、II组、III组中造模组和对照组的血生化指标，通过肾脏切片评估各组肾小管损伤程度和草酸钙晶体形成情况。结果：电镜下对照II组尿液中为小尺寸的圆钝颗粒晶体，造模II组尿液中为多棱角尖锐晶体，尺寸较大，符合正常人和肾结石患者尿液中草酸钙纳米晶体的变化特点。各造模组相较于对应的对照组均呈现血BUN水平上升，有统计学意义(P < 0.05)。肾脏病理结果显示各造模组均表现出肾小管扩张以及管腔中存在草酸钙晶体沉积，但造模II组和造模III组肾脏切片中可见的晶体沉积情况相较于造模I组更为明显。结论：C57BL/6N小鼠的模型组合在肾草酸钙纳米晶体造模上的表现优于其他两组。

Abstract: Objective: To investigate the advantages and disadvantages of nanocrystal modeling in three animal models of renal calcium oxalate stones. Methods: A total of 20 SD rats, 20 C57BL/6N mice, and 20 KM mice were divided into six groups. Model Group I consisted of 10 SD rats, administered with 1% ethylene glycol + 2% ammonium chloride (2 ml) via gavage for 28 days. Control Group I consisted of 10 SD rats, fed conventionally and administered with 2 ml of normal saline via gavage for 28 days. Model Group II consisted of 10 C57BL/6N mice, injected intraperitoneally with 100 mg/kg glyoxylic acid for 7 days. Control Group II consisted of 10 C57BL/6N mice, injected intraperitoneally with an equal volume of normal saline for 7 days. Model Group III consisted of 10 KM mice, injected intraperitoneally with 80 mg/kg glyoxylic acid for 7 days. Control Group III consisted of 10 KM mice, injected intraperitoneally with an equal volume of normal saline for 7 days. The morphology and aggregation of nanocrystals in the urine of each group were observed under an electron microscope. Blood biochemical indicators were compared between the model and control groups in Groups I, II, and III. Renal tissue sections were used to assess the degree of renal tubular injury and calcium oxalate crystal formation in each group. Results: Under the electron microscope, Control Group II showed small, rounded, and blunt granular crystals in the urine, while Model Group II exhibited larger, multi-angled, and sharp crystals, consistent with the characteristics of calcium oxalate nanocrystals in the urine of healthy individuals and kidney stone patients. Compared to their respective control groups, all model groups showed a statistically significant increase in blood BUN levels (P < 0.05). Renal pathology results revealed renal tubular dilation and calcium oxalate crystal deposition in the lumen of all model groups. However, crystal deposition in the renal sections of Model Group II and Model Group III was more pronounced than in Model Group I. Conclusion: The model combination of C57BL/6N mice demonstrated superior performance in modeling renal calcium oxalate nanocrystals compared to the other two groups.