当归补血汤配伍人参调控Notch信号通路改善单侧输尿管梗阻大鼠肾间质纤维化的机制  

The mechanism of Danggui Buxue Decoction combined with Ginseng in improving renal interstitial fibrosis in rats with unilateral ureteral obstruction by regulating the Notch signaling pathway

作　　者：邱赛悦 唐录 骆美秀 朴松兰 王颖航[4] 潘志[1] QIU Saiyue;TANG Lu;LUO Meixiu;PIAO Songlan;WANG Yinghang;PAN Zhi(Jilin Ginseng Academy,Changchun University of Chinese Medicine,Jilin Changchun 130117,China;College of Integrative Medicine,Changchun University of Chinese Medicine,Jilin Changchun 130117,China;College of Clinical Medicine,Changchun University of Chinese Medicine,Jilin Changchun 130117,China;Department of Rheumatoloy,the First Affiliated Hospital of Changchun University of Chinese Medicine,Jilin Changchun 130117,China)

机构地区：[1]长春中医药大学人参科学研究院,吉林长春130117 [2]长春中医药大中西医结合学院,吉林长春130117 [3]长春中医药大临床医学院,吉林长春130117 [4]长春中医药大学第一附属医院风湿病科,吉林长春130117

出　　处：《中国医院药学杂志》2025年第2期128-134,共7页Chinese Journal of Hospital Pharmacy

基　　金：吉林省科技发展计划项目(编号:20230508065RC);吉林省科技发展计划项目(编号:212558JC010388146);吉林省科技发展计划项目(编号:20210101235JC);国家自然科学基金项目(编号:82074324)。

摘　　要：目的:探讨当归补血汤配伍人参调控Notch信号通路改善单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾间质纤维化(renal interstitial fibrosis,RIF)的作用机制。方法:将56只SPF级Wistar大鼠随机分为假手术(Sham)组、UUO组、氯沙坦钾(RX)组、当归补血汤(DBD)组(3.75 g·kg^(-1)、7.5 g·kg^(–1))、当归补血汤配伍人参(GDBD)组(4.4 g·kg^(-1)、8.8 g·kg^(-1))。Sham组大鼠剥离输尿管,不结扎,其余各组大鼠进行单侧输尿管结扎,构建UUO大鼠RIF模型。采用生化分析仪检测血清中BUN和Cr含量;ELISA检测大鼠血清中TGF-β1、TNF-α、α-SMA的含量;HE、Masson染色观察肾组织病理变化和胶原纤维沉积情况;PCR和Western blot检测大鼠肾组织中Notch1、JAG1、HES1 mRNA和蛋白表达情况。结果:与Sham组相比,UUO组大鼠肾功能异常,肾脏损伤和纤维化的关键指标TGF-β1、TNF-α、α-SMA表达升高,Notch1、JAG1、HES1 mRNA和蛋白表达升高;与UUO组相比,各给药组指标变化趋势与上述相反;且与DBD组比较,GDBD组BUN、Cr、α-SMA、Notch1、JAG1和HES1差异有统计学意义。结论:人参对DBD延缓RIF具有增效作用,GDBD可能通过调控Notch信号通路,降低TGF-β1的表达,对延缓UUO大鼠RIF起着重要作用。OBJECTIVE To investigate the mechanism of Danggui Buxue Decoction combined with Ginseng in improving renal interstitial fibrosis(RIF) in rats with unilateral ureteral obstruction(UUO) by regulating the Notch signaling pathway.METHODS A total of 56 Wistar rats in the specific pathogen free(SPF) level were randomly divided into sham operation(Sham) group,UUO group,losartan potassium(RX) group,Danggui Buxue Decoction(DBD) group(3.75 g·kg^(–1),7.5g·kg^(–1)),and Danggui Buxue Decoction combined with Ginseng(GDBD) group(4.4 g·kg^(–1),8.8 g·kg^(–1)).Rats in the Sham group were stripped of the ureter without ligation,and those in the remaining groups were subjected to unilateral ureteral ligation to construct a RIF model in rats with UUO.Serum blood urea nitrogen(BUN) and creatinine(Cr) were detected by biochemical analyzer.Serum TGF-β1,TNF-α and α-SMA in rats were detected by Enzyme-linked immunosorbent assay(ELISA).H&E and Masson's trichrome staining were used to observe the pathological changes and collagen fiber deposition of the kidney tissue.polymerase chain reaction(PCR) and Western blot were applied to detect the mRNA and protein levels of Notch1,JAG1 and HES1 in rat kidney tissue,respectively.RESULTS Compared with Sham group,rats in the UUO group had abnormal renal function,increased serum levels of kidney injury and fibrosis markers(TGF-β1,TNF-α,α-SMA),and upregulated mRNA and protein levels of Notch1,JAG1 and HES1.Compared with the UUO group,opposite changing trends were observed in rats with drug administration.There were significant differences in the levels of BUN,Cr,α-SMA,Notch1,JAG1 and HES1 between DBD and GDBD groups.CONCLUSION Ginseng has a synergistic effect on DBD in delaying RIF.GDBD plays an important role in delaying RIF in UUO rats by downregulating TGF-β1 and regulating the Notch signaling pathway.

关 键 词：当归补血汤 人参 NOTCH信号通路 单侧输尿管梗阻 肾间质纤维化 

分 类 号：R965[医药卫生—药理学]