摘要
目的探讨褪黑素对顺铂(cisplatin,CP)诱导的小鼠急性肾损伤(acute kidney injury,AKI)肾组织中Ki67、髓过氧化物酶(myeloperoxidase,MPO)蛋白表达的影响。方法将40只SPF级雄性C57BL/6J小鼠随机分为对照组(Control组)、模型组(Cisplatin组)、治疗组(Cis+Mel组)及褪黑素组(Mel组),每组10只。Cisplatin组和Cis+Mel组采用腹腔一次性注射CP(15 mg·kg^(-1))建立小鼠AKI模型,Cis+Mel组在注射CP 2 h后腹腔注射褪黑素(20 mg·kg^(-1)),每日1次,连续给药3 d,Mel组一次性腹腔注射褪黑素(20 mg·kg^(-1)),观察各组小鼠精神状态及每天体质量。取小鼠肾脏,用质量分数4%多聚甲醛溶液固定,苏木精-伊红(HE)染色观察小鼠肾组织形态学改变,免疫组化法检测肾组织中Ki67、MPO蛋白表达。结果与Control组比较,Cisplatin组小鼠体质量下降,差异有统计学意义(P<0.001),肾组织中肾小管上皮细胞死亡、脱落,肾小球内充血水肿、炎症细胞浸润,肾组织中Ki67、MPO蛋白表达升高,差异有统计学意义(P<0.001);与Cisplatin组比较,Cis+Mel组小鼠体质量增高,差异有统计学意义(P<0.001),肾小管上皮细胞坏死、肾小球充血水肿明显减轻,炎症细胞浸润减少,肾组织中Ki67、MPO蛋白表达降低,差异有统计学意义(P<0.05)。结论褪黑素可通过降低肾组织中Ki67、MPO蛋白表达,对CP诱导的AKI小鼠肾脏具有保护作用。
Objective To investigate the effects of melatonin on the expression of Ki67 and MPO in acute kidney injury mice induced by cisplatin.Methods Forty SPF male C57BL/6J mice were randomly divided into control group,model group(Cisplatin group),treatment group(Cis+Mel group)and melatonin group(Mel group),10 mice in each group.Cisplatin group and Cis+Mel group were given intraperitoneal injection of CP(15 mg·kg^(-1))to establish mouse AKI model,while Cis+Mel group received intraperitoneal injection of melatonin(20 mg·kg^(-1))2 h after CP injection,once a day for 3 consecutive days,and the Mel group was given a one-time intraperitoneal injection of melatonin(20 mg·kg^(-1)).The mental state and daily body weight of the mice in each group were observed.The kidneys of mice were taken and fixed with 4%paraformaldehyde solution.Hematoxylin-eosin(HE)staining was used to observe the morphological changes of mouse kidneys.Immunohistochemistry was used to detect the protein expressions of Ki67 and MPO in kidney tissue.Results Compared with the control group,the body weight of the mice in the Cisplatin group decreased,and the difference was statistically significant(P<0.001),and the death and shedding of renal tubular epithelial cells,the congestion and edema in the glomerulus,and the infiltration of inflammatory cells were observed in the Cisplatin group.Compared with the control group,the expressions of Ki67 and MPO in renal tissue of Cisplatin group were increased,and the difference was statistically significant(P<0.001).Compared with Cisplatin group,Cis+Mel group had increased body weight(P<0.001)and decreased Ki67 and MPO expressions(P<0.05)in kidney tissue,and tubular epithelial cell necrosis,reduced glomerular congestion and edema,and reduced inflammatory cell infiltration were found in the control group.Conclusion Melatonin can protect the kidney of cisplatin-induced acute kidney injury by reducing the expressions of Ki67 and MPO.
作者
李宁宁
孙韬
雷延飞
李晓英
马香芹
杨亮
LI Ningning;SUN Tao;LEI Yanfei;LI Xiaoying;MA Xiangqin;YANG Liang(Department of Basic Medicine,Henan Medical College,Zhengzhou Henan 451191,China;Department of Medicine,Henan Medical College,Zhengzhou Henan 451191,China;Department of Medical Laboratory Science,Henan Medical College,Zhengzhou Henan 451191,China)
出处
《河南医学高等专科学校学报》
2022年第4期387-391,共5页
Journal of Henan Medical College
基金
河南省科技攻关计划项目(212102310704)。