基于Notch信号通路探讨灯盏花素片对腺嘌呤所致肾纤维化大鼠的改善作用  

Therapeutic Effects of Breviscapine Tablets on Renal Fibrosis Induced by Adenine in Rats Based on Notch Signaling Pathway

作　　者：史晶晶[1] 王灿[2] 贺嘉 张思森 SHI Jingjing;WANG Can;HE Jia;ZHANG Sisen(Henan University of Chinese Medicine,Zhengzhou 450046;The Fifth People’s Hospital of Henan University of Chinese Medicine,Zhengzhou 450000)

机构地区：[1]河南中医药大学,郑州450046 [2]河南中医药大学第五临床医学院,郑州450000

出　　处：《中药药理与临床》2024年第2期29-34,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：河南省高等学校青年骨干教师培养计划项目(编号:2020GGJS108);中原学者工作站项目(编号:224400510011);河南省博士后科研资助项目(编号:HN2022079);河南省中医药科学研究专项课题(编号:2022ZY1184)。

摘　　要：目的:本研究旨在探究灯盏花素片对大鼠肾纤维化的改善作用,并初步探讨可能的潜在作用机制。方法:将SD大鼠分为正常对照组、模型对照组、秋水仙碱0.45 mg/kg组、灯盏花素片5.5、11、22 mg/kg组。造模大鼠采用灌胃给药腺嘌呤建立大鼠肾纤维化模型,模型成功后,各组灌胃给予相应药物或蒸馏水,1次/d,连续30 d。末次给药2 h后,深度麻醉大鼠,取血,用于检测血清中尿素氮(BUN)和肌酐(Scr)含量;取出肾脏,检测肾脏指数;苏木精伊红染色(HE)和马松(Masson)染色法观察肾脏组织病理形态学变化;免疫组化法和RT-PCR法检测肾脏中Notch1、Jagged1、Hes1蛋白和mRNA表达。结果:和正常对照组比较,模型对照组大鼠肾脏指数、血清BUN和Scr含量显著升高(P<0.01),而BUN/Scr比值明显降低(P<0.05);肾脏组织HE染色见肾小管结构破坏,炎症细胞浸润,Masson染色呈现蓝色阳性染色面积增加,肾脏中Notch1、Jagged1、Hes1蛋白及mRNA表达显著上调(P<0.01);与模型对照组相比,灯盏花素片各组均能明显降低肾脏指数及血清中BUN、Scr含量(P<0.05),显著增加BUN/Scr值(P<0.01),改善肾脏病理形态中纤维化病变,下调肾脏中的Notch1、Jagged1、Hes1蛋白及mRNA表达(P<0.01)。结论:灯盏花素片能够减轻腺嘌呤诱导的大鼠肾功能损伤,在一定程度上改善肾间质纤维化,抑制Notch信号通路可能是其作用机制。Objective:To study the therapeutic effects of breviscapine tablets on renal fibrosis in rats and explore its potential mechanisms.Methods:SD rats were divided into the following groups:blank control,model control,colchicine group(0.45 mg/kg),and breviscapine tablet groups(5.5,11,and 22 mg/kg).The rat model of renal fibrosis was established by intragastric administration of adenine,the rats were intragastrically administered with breviscapine tablet suspension once a day,for 30 days.Two hours after the final administration,the rats were anesthetized,and their blood samples were collected to measure the content of serum creatinine(Scr)and blood urea nitrogen(BUN).The kidney was collected to determine the kidney index,and the pathologic changes of renal tissue were observed through hematoxylin-eosin(HE)staining and Masson’s staining.Immunohistochemistry and RT-PCR were performed to measure the protein and mRNA expressions of Notch1,Jagged,and Hes1 in renal tissue.Results:Compared with the blank control group,the model control group showed a significant increase in kidney index,BUN,and Scr content(P<0.01),while the BUN/Scr ratio decreased greatly(P<0.05).According to HE staining results of renal tissue,disrupted renal tubular structures and infiltration of inflammatory cells were observed.Masson’s staining result showed that the blue positive staining area was increased,and the protein and mRNA expression levels of Notch1,Jagged1,and Hes1 were significantly up-regulated(P<0.01).Compared with the model control group,the kidney index and the content of BUN and Scr were significantly decreased in breviscapine tablet groups(P<0.05),and the BUN/Scr ratio significantly increased (P < 0.01). Furthermore, the severity of renal fibrosis wasimproved according to the pathologic changes of the kidney. The protein and mRNAexpression levels of Notch1, Jagged1, and Hes1 in the kidney were down-regulatedsignificantly (P < 0.01). Conclusions: Breviscapine tablets can alleviate adenineinducedrenal functional injury in rats and imp

关 键 词：灯盏花素片 腺嘌呤 肾纤维化 NOTCH信号通路 

分 类 号：R285.5[医药卫生—中药学]