Abstract: Objective This paper aimed to study the synergistic effect and mechanism of lemon-dark plum extract on the prevention of renal calcium oxalate calculus, so as to provide a theoretical basis for further research and clinical application in the prevention and treatment of renal stone. Methods A total of 50 rats (body weight 200-250 g) were divided into five groups by the random number table method: group A (control group), group B (calculus group), group C (lemon extract group), group D (dark plum extract group), and group E (lemon-dark plum extract group). After modeling and dosing for 4 weeks, 24-hour urine volume and urine related indexes, blood creatinine, urea nitrogen, and other biochemical indexes were measured. The crystal deposition and pathological changes of rat kidney were detected. The expression of osteopontin in renal tissue was detected by immunohistochemistry. Independent sample t test was used for measurement data, and rank sum test was used for ranked data. Results The urine volume and urine creatinine in group B decreased significantly [(11.42±1.70) ml and (4.94±1.23) mmol/24 h], while the three kinds of extracts restored the urine volume and increased the urine creatinine level [(15.58±1.61) ml, (15.70±1.69) ml, (16.43±1.55) ml; (6.21±1.17) mmol/24 h, (6.86±2.06) mmol/24 h, (7.40±1.26) mmol/24 h] (all P<0.05). Urinary calcium, uric acid, and oxalic acid in the urine of group B increased significantly [(80.57±12.00) μmol/24 h, (2.20±0.39) mmol/24 h, and (76.98±11.89) μmol/24 h], and the lemon-dark plum extract reduced the three indexes [(35.85± 5.57) μmol/24 h, (1.68±0.16) mmol/24 h, and (56.85±8.34) μmol/24 h], and its effect was significantly better than that of single drug extract (all P<0.05). The three kinds of extracts all reduced the levels of blood creatinine and urea nitrogen in stone rats. The renal tubular lumen of the rats in group B was significantly expanded, and flake or mass calcium oxalate crystals could be seen; the three kinds of extracts significantly improved the crystal deposition and lumen expansion. The extracts of lemon and dark plum significantly down-regulated the expression of osteopontin induced by lithogenesis. Conclusion The lemon-dark plum extract may reduce the occurrence of renal calculus and prevent the recurrence of renal calculus by reducing the content of blood urea nitrogen and creatinine, increasing the level of urine pH, increasing the micturition and creatinine excretion of rats, and inhibiting the formation of renal calcium oxalate crystals.

Key words: Lemon, Dark plum, Renal calculus, Calcium oxalate

摘要： 目的 本文旨在通过研究柠檬乌梅提取液对预防肾草酸钙结石产生的协同效应及其作用机制，为进一步研究和临床预防和治疗肾结石的应用提供理论基础。方法 将 50只大鼠（体质量 200～250 g）按随机数字表法分为5组，A组（对照组）、B组（成石组）、C组（柠檬提取液组）、D组（乌梅 提取液组）、E组（柠檬乌梅提取液组），造模和加药处理4周检测大鼠24 h尿量和尿液相关指标，检测血液肌酐、尿素氮等生化指标；检测大鼠肾脏结晶沉积和病理学改变；通过免疫组织化学方法检测肾组织骨桥蛋白的表达水平。计量资料组间比较用独立样本t检验，等级资料采用秩和检验。结果 B 组大鼠的尿量和尿液肌酐显著下降［（11.42±1.70）ml、（4.94±1.23）mmol/24 h］，而C组、D组、E组3组均能恢复大鼠的尿量和提高尿液肌酐水平［（15.58±1.61）ml、（15.70±1.69）ml、（16.43±1.55）ml；（6.21± 1.17）mmol/24 h、（6.86±2.06）mmol/24 h、（7.40±1.26）mmol/24 h］（均 P<0.05）；B 组尿液中的尿钙、尿酸和尿草酸明显增加［（80.57±12.00）μmol/24 h、（2.20±0.39）mmol/24 h、（76.98±11.89）μmol/24 h］，柠檬乌梅提取液处理能够下调这 3 项指标［（35.85±5.57）μmol/24 h、（1.68±0.16）mmol/24 h、（56.85± 8.34）μmol/24 h］，效果比单药提取液显著（均P<0.05）。C组、D组、E组3组均能降低结石大鼠的血肌酐和尿素氮含量；B组大鼠肾小管管腔明显扩张，可见片状或团状草酸钙结晶，C组、D组、E组3组能够明显改善结晶沉积和管腔扩张的情况；柠檬、乌梅提取液能够显著下调成石诱导肾脏骨桥蛋白的表达。结论 柠檬乌梅提取液可能通过降低血尿素氮和肌酐含量，提高尿液pH水平，增加大鼠的排尿量和肌酐排泄，抑制肾脏草酸钙结晶的形成，从而减少肾结石的发生和预防肾结石的复发。

关键词: 柠檬, 乌梅, 肾结石, 草酸钙