段争 1杨丹宁 1曹瑞琪 1聂亚珍 1陈成 1刘伟丽 2陈照立2
作者信息
- 1. 天津中医药大学研究生院,天津 301617||军事科学院军事医学研究院,天津 300050
- 2. 军事科学院军事医学研究院,天津 300050
- 折叠
摘要
Abstract
[Objective]To investigate the protective mechanism of asiaticoside(AS)against renal injury in rats exposed to chronic hypobaric hypoxia.[Methods]A simulated high-altitude environment(approximately 6 000 meters,with a partial pressure of oxygen of about 11.0 kPa for 23 h/d)was created using an animal hypobaric hypoxia chamber.Thirty-two Wistar rats were randomly divided into four groups(n=8 each):a normoxic control group(Normoxia),a hypobaric hypoxia model group(HH),a low-dose asiaticoside intervention group(HH+40AS,40 mg/kg),and a high-dose asiaticoside intervention group(HH+80AS,80 mg/kg).After the experiment,the following assessments were performed:24-hour urinary indices,serum creatinine(Scr),and blood urea nitrogen(BUN)levels;renal histopathological changes observed via hematoxylin-eosin(HE)staining,Masson's trichrome staining,and periodic acid-Schiff(PAS)staining;renal cell death detected by TUNEL staining;oxidative stress levels in serum and renal tissue measured using kits for superoxide dismutase(SOD),malondialdehyde(MDA),and lactate dehydrogenase(LDH);serum and renal tissue levels of inflammatory factors[interleukin-1β(IL-1β),interleukin-18(IL-18)]measured by enzyme-linked immunosorbent assay(ELISA);and protein expression levels of NOD-like receptor thermal protein domain-associated protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),Caspase-1,cleaved Caspase-1(p20),gasdermin D(GSDMD),and its N-terminal fragment(GSDMD-N)in renal tissue determined by Western blot.[Results]Compared with the Normoxia group,the HH group showed significant renal histopathological damage,increased 24-hour urinary indices,Scr,and BUN,a higher number of TUNEL-positive cells,upregulated levels of MDA,LDH,IL-1β,and IL-18 in both renal tissue and serum,significantly increased protein expression of NLRP3,ASC,cleaved Caspase-1(p20),and GSDMD-N(P<0.01),and significantly decreased SOD levels in renal tissue and serum(P<0.01).Asiaticoside intervention,especially in the HH+80AS group,markedly improved renal function indicators,alleviated renal histopathological damage and cell death,reduced inflammatory factor levels,and dose-dependently inhibited the activation of the NLRP3 inflammasome and the cleavage of downstream GSDMD.[Conclusion]Asiaticoside can alleviate pyroptosis and oxidative stress in rat renal tissue by inhibiting the activation of the NLRP3/Caspase-1/GSDMD signaling pathway,thereby mitigating renal tissue injury and fibrosis induced by chronic hypobaric hypoxia.关键词
积雪草苷/高原低压低氧/肾脏损伤/NLRP3/焦亡Key words
asiaticoside/hypobaric hypoxia/kidney injury/NLRP3/pyroptosis分类
医药卫生
