摘要
考察金水宝片对顺铂诱导大鼠急性肾损伤的防治作用及机制。分别采用单次腹腔注射顺铂5 mg/kg和连续5 d静脉注射顺铂2 mg/kg诱导大鼠急性肾损伤模型。观察大鼠急性肾损伤模型分别经预防性或治疗性给予金水宝片后的肾功能的变化,给药结束后进行肾脏组织病理学检查,并检测肾脏肿瘤坏死因子-α(TNF-α)和活性氧(ROS)的含量、半胱天冬酶3(Caspase 3)活性以及t-p38、p-p38、Bax及Bcl-2的蛋白表达。结果显示,金水宝片预防性给药和治疗性给药均能显著抑制顺铂诱导的大鼠急性肾损伤模型的血清尿素氮(BUN)和肌酐(CRE)水平的上升,显著增加肾脏肌酐清除率,显著改善肾小管变性和炎症浸润,且预防性给药的起效时间较治疗性给药缩短。同时两种给药方式均能显著降低肾脏TNF-α、ROS含量以及Caspase 3活性。Western blot结果显示,金水宝片能显著减少肾脏中p-p38、t-p38的蛋白表达,显著增大Bcl-2/Bax比值。研究结果表明,金水宝预防性给药和治疗性给药均能通过改善肾功能和肾脏组织病理变化,以达到对顺铂所致急性肾损伤的防治作用,且其作用机制可能与金水宝抑制TNF-α,抑制ROS-p38MAPK-Caspase 3通路,进而抑制细胞凋亡有关。
This study aimed to observe the therapeutic effect and mechanism of Jinshuibao tablet on acute renal injury induced by cisplatin.Acute renal injury models in SD rats were induced separately by single intraperitoneal injection of cisplatin(5 mg/kg)and intravenous injection for 5 consecutive days at a dosage of 2 mg/kg per day.The renal function and renal histopathological changes were observed in rat acute renal injury models after prevention and treatment with Jinshuibao tablet,respectively.The content of tumor necrosis factor(TNF-α)and reactive oxygen species(ROS),the activity of Caspase 3 and the expression of t-p38,p-p38,Bax and Bcl-2 in the kidneys were detected.The results showed that preventive and therapeutic administration of Jinshuibao tablets could both significantly inhibit the increase of the blood urea nitrogen(BUN)and creatinine(CRE),increase the creatinine clearance rate,reduce the contents of TNF-αand ROS,and decrease the activity of Caspase 3 in acute renal injury models induced by cisplatin.The renal histopathological results showed that Jinshuibao tablets could significantly reduce renal histopathology scores,ameliorate renal tubule degeneration and inflammatory infiltration.Western blot results showed that Jinshuibao tablets could significantly decrease the expression of t-p38 and p-p38,while increasing the Bcl-2/Bax ratio in the kidneys.These results suggested that preventive and therapeutic administration of Jinshuibao tablets could both improve renal function and pathological changes of renal tissue,which might be related to the inhibition of TNF-αand the ROS-p38 MAPK-Caspase3 pathway and thus inhibition of apoptosis.
作者
刘学武
周志敏
姜德建
龙利
LIU Xuewu;ZHOU Zhiming;JIANG Dejian;LONG Li(Hunan Provincial Research Center for Safety Evaluation of Drugs,Changsha 410331;Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs,Changsha 410331;Nephrology Department of the Third People′s Hospital of Hubei Province,Wuhan 430033,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2020年第1期76-83,共8页
Journal of China Pharmaceutical University
基金
湖南省重点研发计划资助项目(No.2018SK2115)。
关键词
金水宝片
顺铂
肾脏损伤
作用机制
Jinshuibao tablets
cisplatin
acute kidney injury
mechanism
