Abstract：
BACKGROUND: Lithium is widely used in the treatment of bipolar disorders and may lead to nephrogenic diabetes insipidus (NDI), following long-term treatment. Metformin is considered the preferred initial therapy for patients with type 2 diabetes mellitus (T2D).
OBJECTIVE: To investigate the protective effect of metformin on the kidney damage caused by lithium administration.
METHODS: Using an animal model of chronic lithium-induced NDI, rats were divided into 4 groups: sham, metformin, lithium, and lithium + metformin. The effects of these treatments were examined using serum electrolytes, blood and tissue total antioxidant status, total oxidant status, the oxidative stress index, urine and blood osmolality, and tissue aquaporin-2 (AQP2) levels. Additionally, histopathological changes, including congestion, hydropic swelling, tubular necrosis, tubular atrophy, and Bowman\'s capsule dilatation, were evaluated. The total histopathological score was obtained by summing the scores for each pathological finding.
RESULTS: In the lithium group, biochemical variables indicating NDI, including sodium, chloride and blood osmolality, increased, and urine osmolality decreased, compared to the sham group. With metformin treatment, the blood osmolality decreased from 328.17 mOsm/kg to 306.33 mOsm/kg, and urine osmolality increased from 349.67 mOsm/kg to 754.50 mOsm/kg (p = 0.004 and p = 0.001, respectively). Tissue AQP2 levels decreased with lithium administration but stabilized with metformin treatment. Additionally, in comparison to the lithium group, the total histopathological score in the metformin group declined from 8.0 to 2.0 (p = 0.002).
CONCLUSIONS: Metformin may help protect the kidneys from lithium-induced NDI through the AQP2 regulating effect and a reduction in oxidative stress.
OBJECTIVE: To investigate the protective effect of metformin on the kidney damage caused by lithium administration.
METHODS: Using an animal model of chronic lithium-induced NDI, rats were divided into 4 groups: sham, metformin, lithium, and lithium + metformin. The effects of these treatments were examined using serum electrolytes, blood and tissue total antioxidant status, total oxidant status, the oxidative stress index, urine and blood osmolality, and tissue aquaporin-2 (AQP2) levels. Additionally, histopathological changes, including congestion, hydropic swelling, tubular necrosis, tubular atrophy, and Bowman\'s capsule dilatation, were evaluated. The total histopathological score was obtained by summing the scores for each pathological finding.
RESULTS: In the lithium group, biochemical variables indicating NDI, including sodium, chloride and blood osmolality, increased, and urine osmolality decreased, compared to the sham group. With metformin treatment, the blood osmolality decreased from 328.17 mOsm/kg to 306.33 mOsm/kg, and urine osmolality increased from 349.67 mOsm/kg to 754.50 mOsm/kg (p = 0.004 and p = 0.001, respectively). Tissue AQP2 levels decreased with lithium administration but stabilized with metformin treatment. Additionally, in comparison to the lithium group, the total histopathological score in the metformin group declined from 8.0 to 2.0 (p = 0.002).
CONCLUSIONS: Metformin may help protect the kidneys from lithium-induced NDI through the AQP2 regulating effect and a reduction in oxidative stress.
摘要：
背景：锂广泛用于双相情感障碍的治疗，并可能导致肾源性尿崩症（NDI），长期治疗后。二甲双胍被认为是2型糖尿病（T2D）患者的首选初始治疗方法。
目的：探讨二甲双胍对补锂肾损害的保护作用。
方法：使用慢性锂诱导的NDI动物模型，将大鼠分为4组：假，二甲双胍,锂，和锂+二甲双胍。使用血清电解质检查这些治疗的效果，血液和组织总抗氧化状态，总氧化剂状态，氧化应激指数，尿液和血液渗透压,和组织水通道蛋白2（AQP2）水平。此外,组织病理学变化,包括拥堵，积水肿胀,肾小管坏死,肾小管萎缩,和鲍曼的胶囊扩张，进行了评估。通过对每个病理发现的评分求和获得总组织病理学评分。
结果：在锂组中，指示NDI的生化变量，包括钠,氯化物和血液渗透压，增加,尿液渗透压下降，与假手术组相比。用二甲双胍治疗，血液渗透压从328.17mOsm/kg下降到306.33mOsm/kg，和尿渗透压从349.67mOsm/kg增加到754.50mOsm/kg（分别为p=0.004和p=0.001）。组织AQP2水平随着锂给药而降低，但随着二甲双胍治疗而稳定。此外,与锂组相比，二甲双胍组的组织病理学总评分从8.0降至2.0(p=0.002).
结论：二甲双胍可能通过AQP2调节作用和减少氧化应激，有助于保护肾脏免受锂诱导的NDI的影响。
目的：探讨二甲双胍对补锂肾损害的保护作用。
方法：使用慢性锂诱导的NDI动物模型，将大鼠分为4组：假，二甲双胍,锂，和锂+二甲双胍。使用血清电解质检查这些治疗的效果，血液和组织总抗氧化状态，总氧化剂状态，氧化应激指数，尿液和血液渗透压,和组织水通道蛋白2（AQP2）水平。此外,组织病理学变化,包括拥堵，积水肿胀,肾小管坏死,肾小管萎缩,和鲍曼的胶囊扩张，进行了评估。通过对每个病理发现的评分求和获得总组织病理学评分。
结果：在锂组中，指示NDI的生化变量，包括钠,氯化物和血液渗透压，增加,尿液渗透压下降，与假手术组相比。用二甲双胍治疗，血液渗透压从328.17mOsm/kg下降到306.33mOsm/kg，和尿渗透压从349.67mOsm/kg增加到754.50mOsm/kg（分别为p=0.004和p=0.001）。组织AQP2水平随着锂给药而降低，但随着二甲双胍治疗而稳定。此外,与锂组相比，二甲双胍组的组织病理学总评分从8.0降至2.0(p=0.002).
结论：二甲双胍可能通过AQP2调节作用和减少氧化应激，有助于保护肾脏免受锂诱导的NDI的影响。
