时珍国医国药2026，Vol.37Issue(16)：3009-3016,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-1602
益肾活血方调控线粒体动力学平衡改善急性肾损伤慢性化的机制研究
Mechanism of Yishen Huoxue Decoction(益肾活血方)in ameliorating in chronic progression of acute kidney injury by regulating mitochondrial dynamic balance
摘要
Abstract
Objective To investigate the protective effect and mechanism of Yishen Huoxue Decoction(益肾活血方,YSHXD)on the chronic progression of acute kidney injury(AKI)by regulating mitochondrial dynamic balance.Methods(1)In vivo experiment:Thirty male Sprague-Dawley rats were randomly divided into five groups(n=6):sham-operated group(Sham),model group(IRI),inhibitor group(Mdivi-1,50 mg/kg),YSHXD high-dose group(YSHXD-H,18.48 g/kg/d),and YSHXD low-dose group(YSHXD-L,4.62 g/kg/d).A rat model of chronic AKI was established using the bilateral renal pedicle clamping method.The Sham and IRI groups received an equal volume of normal saline.Rats were sacrificed on day 28 after surgery.Serum creatinine(CRE)and blood urea nitrogen(BUN)levels were measured.Renal histopathological changes were assessed by HE and Masson staining.Mitochondrial ultra-structural changes were observed by electron microscopy.Protein expression levels of Drp1,Fis1,Opa1,and Mfn2 were detected by Western blot(WB).(2)In vitro experiment:Human renal tubular epithelial cells(HK-2)were cultured and divided into Control,H/R,Mdivi-1,and YSHXD groups.A hypoxia-reoxygenation(H/R)model was established to induce cell injury.Cells were treated with YSHXD-containing serum or Mdivi-1 for 24 hours.Cell morphology and viability were assessed.Malondialdehyde(MDA),superoxide dismutase(SOD),and ATP activity were measured by ELISA.α-SMA expression was detected by immunofluorescence.Protein expres-sion levels of Drp1,Fis1,Opa1,and Mfn2 were determined by WB.Results In vivo experiment:Compared with the Sham group,the IRI group showed significantly increased renal function indices(CRE,BUN),severe renal histopathological damage,collagen fiber deposition,mitochondrial structural disruption,upregulation of Drp1 and Fis1 expression,and downregulation of Opa1 and Mfn2 expression(P<0.05,P<0.01).Compared with the IRI group,the YSHXD-H group significantly improved renal function,alleviated renal histopathological injury and fibrosis,repaired mitochondrial structure,and reversed the abnormal expression of the aforementioned proteins(P<0.05,P<0.01).In vitro experiment:H/R induction decreased HK-2 cell viability,increased MDA levels,decreased SOD and ATP activity,upregulated α-SMA expression,upregulated Drp1 and Fis1 expression,and downregulated Opa1 and Mfn2 expression(P<0.05,P<0.01).Compared with the H/R group,YSHXD-containing serum improved cell viability,reduced MDA levels,increased SOD and ATP activity,downregulated α-SMA expression,downregulated Drp1 and Fis1 expression,and upregulated Opa1 and Mfn2 expression(P<0.05,P<0.01).Conclusion YSHXD may delay the chronic progression of AKI by maintaining mito-chondrial dynamic stability,reducing oxidative stress,and alleviating renal tubular epithelial cell injury,possibly through downregulat-ing Drp1 and Fis1 expression and upregulating Opa1 and Mfn2 expression.关键词
急性肾损伤/益肾活血方/线粒体动力学/缺血/再灌注损伤/肾小管上皮细胞Key words
Acute kidney injury/Yishen Huoxue Decoction(益肾活血方)/Mitochondrial dynamics/Ischemia-reperfusion injury/Renal tubular epithelial cells分类
医药卫生引用本文复制引用
罗芳,姚春,杜谋英,石晓冬,吕沁珂,翁雪莹,李凯,钟建..益肾活血方调控线粒体动力学平衡改善急性肾损伤慢性化的机制研究[J].时珍国医国药,2026,37(16):3009-3016,8.基金项目
国家自然科学基金(82260866) （82260866）
广西自然科学基金(2023GXNSFAA026245) （2023GXNSFAA026245）
国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023166) （zyyzdxk-2023166）
白求恩·圣创未来-慢性肾病研究基金(SCWLKY-050-001) （SCWLKY-050-001）
