顺铂诱导肾损伤模型在C57BL/6小鼠J和N亚型中的差异性研究  

Differences in susceptibility to cisplatin-induced kidney injury in J and N subtypes of C57BL/6 mice

作　　者：王婵 邱会琴 唐亚婷 朱方媛 范彦英 杨彩红 WANG Chan;QIU Hui-qin;TANG Ya-ting;ZHU Fang-yuan;FAN Yan-ying;YANG Cai-hong(Dept of Pharmacology,Basic Medical Sciences Center,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学基础医学院药理学教研室,山西太原030001

出　　处：《中国药理学通报》2024年第4期792-797,共6页Chinese Pharmacological Bulletin

基　　金：山西省自然科学基金资助项目(No 201901D111198,202303021211125);山西医科大学教学改革项目(No SZL20200301)。

摘　　要：目的探讨C57BL/6 J和N亚型小鼠在顺铂诱导肾损伤模型中的易感性差异,为选择药物肾损伤模型提供理论依据。方法雄性C57BL/6小鼠J和N两种亚型,各随机分为正常组(Control)、模型组(cisplatin,CDDP)。模型组腹腔注射顺铂(3.33 mg·kg^(-1)),隔天给药,持续2周,记录小鼠体重变化、存活率;检测Scr、BUN和β2-MG评价肾功能;HE、Masson和PAS染色法观察肾皮质病理改变。IL-6、IL-1β和IL-18等炎症因子检测顺铂导致的肾脏炎症反应。结果与Control组相比,CDDP组两种亚系小鼠Scr、BUN和β2-MG均明显升高;组织学结果显示肾小管损伤,胶原纤维化和糖原沉积均增加;IL-6、IL-1β和IL-18炎症因子含量和肾皮质蛋白表达均明显升高。C57BL/6N与C57BL/6J系小鼠比较,C57BL/6N系小鼠肾功能指标Scr和BUN均值明显偏高(P<0.01),组织学评分各病理损伤较C57BL/6J亚系小鼠明显偏高,反映纤维化的Masson染色差异具有统计学意义(P<0.01);IL-6、IL-1β和IL-18均值明显偏高,但差异无统计学意义。结论C57BL/6 J和N亚型小鼠均可使用顺铂诱导成功肾损伤模型,相比于C57BL/6J小鼠,C57BL/6N亚系小鼠在肾功能、组织学以及炎症因子等方面损伤明显,提示C57BL/6N亚系小鼠更适于作为药物或者其他肾功能损伤模型的建立。Aim To investigate the differences of cisplatin-induced kidney injury in susceptibility of C57BL/6 J and N subtypes,and to provide theoretical basis for selecting drug-induced kidney injury models.Methods Male C57BL/6 mice of J and N subtypes,were randomly divided into the normal control group and the CDDP group.The model group were intraperitoneally injected with CDDP of 3.33 mg every other day in 2 weeks.Body weight and survival rate were recorded for each group of mice.The levels of creatinine(CRE),blood urea nitrogen(BUN)andβ2-microglobulin(β2-MG)were detected to evaluate renal function.IL-6,IL-1βand IL-18 inflammatory factors were used to detect kidney inflammation in CDDP-induced kidney injury.Hematoxylin-eosin(HE)staining,Masson staining and periodic acid-Schiff(PAS)staining were used to observe the pathological changes of renal cortex.Results Compared with the normal control group,the contents of Scr,BUN,andβ2-MG in serum of the CDDP group were significantly increased(P<0.01).Histological results showed increased renal tubular injury,collagen fibrosis(P<0.01),and glycogen deposition.Concurrently,the contents and renal cortex protein expression levels of IL-1β,IL-6,and IL-18 were significantly elevated(P<0.01 or P<0.05).In C57BL/6N compared to C57BL/6J mice,the mean values of Scr and BUN in C57BL/6N mice were notably higher(P<0.01).The histological scores for each pathological injury in the mice were significantly higher than those in C57BL/6J mice,particularly in the Masson staining of fibrosis(P<0.01).Although the mean values of IL-6,IL-1βand IL-18 were significantly higher in C57BL/6N mice,but the difference was not statistically significant.Conclusions Both C57BL/6J and N subtype mice can be successfully induced renal injury model with cisplatin.Compared with C57BL/6J mice,C57BL/6N mice exhibited marked renal function impairment as well as histological and inflammatory factors-related damage.This experiment suggests that C57BL/6N subtype mice are more suitable for the establishment of drug or oth

关 键 词：顺铂 亚急性肾损伤 C57BL/6亚系 炎症因子 IL-6 IL-1β IL-18 

分 类 号：R-332[医药卫生] R322.61R364.5R692.5R979.19