摘要
目的:研究山莨菪碱对顺铂诱导的急性肾损伤大鼠Toll样受体(TLR4)/核因子κB(NF-κB)信号通路的调节作用。方法:90只大鼠随机分为正常对照组、急性肾损伤组、山莨菪碱低、中、高剂量组以及阳性对照组,除正常对照组外,其余大鼠腹腔注射顺铂建立急性肾损伤大鼠模型,山莨菪碱低、中、高剂量组分别按照2.5 mg/kg、5 mg/kg、10 mg/kg腹腔注射给予大鼠山莨菪碱,阳性对照组腹腔注射1.0 mg/kg安磷汀,正常对照组及急性肾损伤组给予生理盐水,1次/d,连续14 d。使用ELISA试剂盒测定大鼠24 h尿蛋白量、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)水平、血清尿素氮(BUN)及肌酐(Cr)水平,苏木精-伊红(HE)染色法对大鼠进行肾组织病理学检查,实时定量PCR(RT-PCR)法检测大鼠肾组织TLR4及NF-κBp65 mRNA水平,免疫印迹(Western blot)法测定大鼠肾组织TLR4及NF-κBp65蛋白水平。结果:山莨菪碱低、中、高剂量组大鼠24 h尿蛋白量、尿NAG水平、血清BUN及Cr水平、肾组织TLR4及NF-κBp65 mRNA水平、肾组织TLR4及NF-κBp65蛋白水平较急性肾损伤组大鼠均降低,差异有统计学意义(P<0.05),且各项指标变化与山莨菪碱剂量表现出依赖性,同时山莨菪碱各剂量组大鼠肾组织病理学明显改善。结论:山莨菪碱能够缓解顺铂诱导的大鼠急性肾损伤状态,改善大鼠肾组织病理学,其机制可能与调节TLR4/NF-κB信号通路有关。
Objective:To study the regulatory effect of anisodamine on Toll-like receptor(TLR4)/nuclear factor κB(NF-κB) signal pathway in cisplatin-induced acute renal injury in rats. Methods:90 rats were randomly divided into normal control group, acute renal injury group, low, middle and high dose anisodamine groups and positive control group. Except for the normal control group, the rat model of renal injury was established by intraperitoneal injection of cisplatin. Anisodamine injection was given to rats in low, middle and high dose anisodamine groups according to 2.5 mg/kg, 5 mg/kg and 10 mg/kg, respectively. The positive control group was intraperitoneally injected with 1.0 mg/kg, while the normal control group and acute renal injury group were given normal saline once a day for 14 days. 24-hour urinary protein, urinary N-acetyl-β-D-glucosaminidase(NAG) level, serum urea nitrogen(BUN) and creatinine(Cr) level were measured by ELISA kit. Renal histopathology was examined by hematoxylin-eosin(HE) staining, and renal tissue TLR4 and NF-κBp65 mRNA levels were detected by real-time quantitative PCR(RT-PCR). The levels of TLR4 and NF-κBp65 protein in rat kidney tissue were measured by immunoblotting(Western blot). Results:24-hour urinary protein, urine NAG level, serum BUN and Cr levels, renal tissue TLR4 and NF-κBp65 mRNA levels, renal tissue TLR4 and NF-κBp65 protein levels in anisodamine low, middle and high dose groups were significantly lower than those in acute renal injury group(P<0.05), and the changes of various indexes were dependent on the dose of anisodamine. At the same time, the renal histopathology of rats in each dose group of anisodamine was significantly improved. Conclusion:Anisodamine can alleviate cisplatin-induced acute renal injury and improve renal histopathology in rats. The mechanism may be related to the regulation of TLR4/NF-κB signal pathway.
作者
彭海萍
吴广礼
PENG Haiping;WU Guangli(Department of Renal Medicine,Xinrui Hospital,Xinwu District,Wuxi,214028)
出处
《中国中西医结合肾病杂志》
2021年第9期769-773,共5页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
“六个一工程”拔尖人才科研项目(No.LGY2017052)。
