摘要
目的探讨柚皮素(naringenin,Nar)对妊娠高血压综合征(pregnancy-induced hypertension syndrome,PIH)肾损伤的影响,并分析其相关的机制。方法在妊娠第8—20 d每天腹腔注射50mg/kg L-NAME,诱导PIH模型;在妊娠第8—20 d,每天口服200 mg/kg Nar作为Nar对照,每天腹腔注射50 mg/kg L-NAME的同时口服200 mg/kg Nar作为PIH的Nar治疗。在妊娠第1、8、12、14、16、18和20 d监测大鼠收缩压。ELISA法检测妊娠第20 d的尿白蛋白和肌酐含量,并计算尿白蛋白排泄率和肌酐清除率。在妊娠第21 d,处死大鼠并收集肾组织,用HE、PAS和Masson染色观察肾组织病理学,评估组织学损伤、肾小球硬化和肾小管间质纤维化严重程度,生化法测定肾组织中MDA、CAT和GSH含量,TUNEL染色以及Cleaved Caspase-3、Bcl-2和Bax免疫组织化学染色评估肾组织凋亡情况;免疫组织化学染色评估肾组织中NRF-2和HO-1表达。结果在PIH大鼠,Nar虽不影响收缩压,但能降低尿白蛋白排泄率和增加肌酐清除率,抑制肾小管上皮细胞凋亡,改善肾小球硬化和肾小管间质纤维化,降低氧化应激水平,并增强肾组织中NRF-2/HO-1活性。结论柚皮素可能通过降低氧化应激水平抑制PIH大鼠的肾损伤。
Objective To investigate the effects of naringenin(Nar)on kidney injury caused by pregnancy-induced hypertension syndrome(PIH)and its mechanism.Methods The PIH model was induced by intraperitoneal injection of 50 mg/kg L-NAME every day from the 8th to 20th days of pregnancy;On the 8th to 20th day of pregnancy,200 mg/kg Nar was orally administered daily as Nar control,and 50 mg/kg L-NAME was intraperitoneally injected daily while 200 mg/kg Nar was orally administered as Nar treatment for PIH.The systolic blood pressure of rats was monitored at gestation days 1,8,12,14,16,18 and 20.The contents of urinary albumin and creatinine of rats in each group were measured by ELISA on the 20th day of gestation,and the excretion rate of urinary albumin and creatinine clearance rate were calculated.On the 21th day of gestation,the rats were sacrificed and the renal tissues were collected;the histopathological changes of the kidneys were observed with HE,PAS and Masson staining,and the degrees of histological dam-age,glomerulosclerosis and renal tubulointerstitial fibrosis were assessed;the contents of MDA,CAT and GSH in renal tissue were determined by biochemical method;renal apoptosis was evaluated by TUNEL staining and immunohistochemical staining for Cleaved Caspase-3,Bcl-2 and Bax;the expression of NRF-2 and HO-1 in renal tissues was assessed by immunohistochemical staining.Results In PIH rats,although Nar did not affect systolic blood pressure,it reduced urinary albumin excretion rate and increased creatinine clearance rate,inhibited apoptosis of renal tubular epithelial cells,improved glomerulosclerosis and tubulointerstitial fibrosis,reduced the level of oxidative stress,and enhanced NRF-2/HO-1 activity in renal tissue.Conclusion Nar may alleviate renal injury in PIH rats by reducing the level of oxidative stress.
作者
刘雨
汤容
王晓霜
Liu Yu;Tang Rong;Wang Xiaoshuang(Department of Obstetrics,Chongqing Traditional Chinese Medicine Hospital,Chongqing 400021;Department of Obstetrics,Affiliated Women’s and Children’s Hospital,University of Electronic Science and Technology of China/Chengdu Women and Children’s Central Hospital,Chengdu 610073)
出处
《中国组织化学与细胞化学杂志》
CAS
CSCD
2022年第4期359-366,共8页
Chinese Journal of Histochemistry and Cytochemistry
关键词
柚皮素
妊娠高血压
肾损伤
氧化应激
NRF-2/HO-1信号通路
Naringenin
pregnancy-induced hypertension syndrome
kidney injury
oxidative stress
NRF-2/HO-1 signaling pathway