阿霉素联合腺嘌呤诱导大鼠病理性衰老模型的建立  

The establishment of a rat model of pathological aging induced by adriamycin combined with adenine

作　　者：张华琴[1] 万凤 唐玥雯 杨汝春[1] 王洲婷 Zhang Huaqin

机构地区：[1]杭州市中医院,310007 [2]浙江中医药大学,310053

出　　处：《浙江临床医学》2022年第9期1269-1271,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省自然科学基金资助项目(LY20H050004);浙江省中医药科技计划重点研究项目(2020ZZ016)。

摘　　要：目的探讨阿霉素联合腺嘌呤诱导大鼠病理性衰老模型的建立.方法采用尾静脉注射阿霉素联合腺嘌呤灌胃诱导大鼠病理性肾衰老(A+X组),以D-半乳糖诱导的衰老模型(D组)及正常大鼠(NC组)为对照.12周后处死大鼠,收集尿液和肾脏组织标本.测定大鼠24 h尿蛋白和肾功能指标;取肾脏,计算肾重与体重指数;检测肾组织匀浆液中丙二醛(Malonic dialdehyde,MDA)水平;采用HE和Masson染色观察肾脏组织病理损伤和纤维化;免疫组化检测肾组织p16^(INK4α)蛋白原位表达;肾组织冷冻切片检测SA-β-GAL活性;透射电镜下观察肾组织超微病理改变.结果D组大鼠和A+X组大鼠肾重/体重指数比正常(NC)组增高,A+X组肾重/体重指数、血肌酐水平均比NC组及D组增高.HE和Masson染色结果显示,A+X组大鼠肾组织中呈现明显的肾间质炎性细胞浸润和纤维化;透射电镜结果显示,A+X组大鼠足细胞轻中度融合;D组和A+X组大鼠肾间质SA-β-GAL和p16^(INK4α)水平均比NC组增加,A+X组肾小球p16^(INK4α)水平比D组增加.结论阿霉素联合腺嘌呤诱导可有效建立肾损伤致病理性衰老大鼠动物模型.Objective To observe the combined induction fect of adriamycin and adenine on renal injury and renal aging in rats.Methods Rat renal injury was induced respectively via the tail vein injection of adriamycin combined with intragastric administration of adenine(A+X).Meanwhile,the aging model induced by D-galactose(D)was used as the control.After 12 weeks,the rats were sacrificed and their urine and kidney tissue samples were collected.24-hour urinary protein and serum renal function indexes of different groups were measured using a biochemical analyzer.Kidney tissues were collected,and the kidney weight and body weight indexes were calculated,the levels of Malonic dialdehyde(MDA)in renal tissue homogenate were detected.HE and Masson staining were used to observe the pathological injury and fibrosis of renal tissue.Immunohistochemical analysis was used to observe the in situ expreson of p16^(INK4α)protein in real tisue.SA-β-GAL was deteted by fozen setion of real tisue.The ulrastructura pathological changes of real tissue were observed under a transmssion electron microscope.ResultsCompared with NC group,the renal weight/body mass index of rats in group D and group A+X was significantly increased.Renal weight/body mass index and serum creatinine of rats in group A+X were significantly higher than that in the normal(NC)group and D group.The results of HE and Masson staining showed there were obvious inflammatory cell infiltration and interstitial fibrosis in the renal tissue of rats in the group.Transmision electron microscopy showed that podocyte fusion was mild to moderate in group A+X.Renal aging markers SA-β-GAL and p16^(INK4α)also increased significanty in rats of D group and A+X group,and the levels of pl6^(INK4α)in glomerular of rats in group A+X were significantly increased compared with group D.Conclusion Adriamycin combined with adenine can effectively establish a rat model of renal injury with pathological renal aging.

关 键 词：阿霉素 腺嘌呤 D-半乳糖 大鼠 肾损伤 

分 类 号：R692[医药卫生—泌尿科学] R-332[医药卫生—外科学]