茯苓酸调控Sirt1/PGC-1α通路改善妊娠高血压大鼠肾损伤的机制OA
Mechanism of pachymic acid in ameliorating renal injury in pregnancy induced hypertension rats by regulating the Sirt1/PGC-1α pathway
目的 基于沉默信息调节因子2同源蛋白1/过氧化物酶体增殖物激活受体γ辅激活因子1α(Sirt1/PGC-1α)通路探究茯苓酸对妊娠高血压(PIH)大鼠肾损伤的作用机制.方法 SD大鼠雌雄合笼喂养制备孕鼠,并通过腹腔注射N-硝基-左旋精氨酸甲酯构建PIH大鼠模型.将PIH大鼠分为模型组、低-茯苓酸(低剂量茯苓酸,10 mg/kg)组、高-茯苓酸(高剂量茯苓酸,20 mg/kg)组、高-茯苓酸+EX527(20 mg/kg茯苓酸+10 mg/kg EX527)组,每组6只.另取6只正常孕鼠为空白组.各组孕鼠每日灌胃或腹腔注射相应药物或溶剂,每日1次,连续28 d.末次给药后,检测各组孕鼠24 h尿蛋白和尾动脉收缩压(SBP),血清中血肌酐(Scr)、尿素氮(BUN)、尿酸(UA)、胱抑素C(Cys-C)水平,肾组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、8-羟基脱氧鸟苷(8-OHdG)含量以及Sirt1、PGC-1α mRNA及蛋白表达水平;同时,通过苏木精-伊红(HE)染色和过碘酸-雪夫染色(PAS)染色评估各组大鼠肾组织病理学变化.结果 与模型组比较,低-茯苓酸组和高-茯苓酸组大鼠24 h尿蛋白,尾动脉SBP,血清中Scr、BUN、UA、Cys-C水平,肾小球硬化指数评分,肾小管损伤评分,肾组织PAS阳性面积百分比及MDA、8-OHdG含量均显著降低(P＜0.05),SOD、GSH-Px含量和Sirt1、PGC-1α mRNA及蛋白表达水平均显著升高(P＜0.05),且高-茯苓酸组变化更明显(P＜0.05);与高-茯苓酸组比较,高-茯苓酸+EX527组孕鼠上述指标变化均显著逆转(P＜0.05).结论 茯苓酸可通过激活Sirt1/PGC-1α通路改善PIH诱导的孕鼠肾损伤.
OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension(PIH)rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α(Sirt1/PGC-1α)pathway.METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L-arginine methyl ester(L-NAME)method.PIH rats were randomly divided into model group,L-pachymic acid(low-dose pachymic acid,10 mg/kg)group,H-pachymic acid(high-dose pachymic acid,20 mg/kg)group,and H-pachymic acid+EX527(20 mg/kg pachymic acid+10 mg/kg EX527)group,with 6 rats in each group.Another 6 normal pregnant rats were selected as blank group.Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily,once a day,for 28 consecutive days.After the last administration,24 h urinary protein and tail artery systolic blood pressure(SBP)were measured in pregnant rats from each group,along with the levels of serum creatinine(Scr),blood urea nitrogen(BUN),uric acid(UA),and cystatin C(Cys-C).The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in renal tissue,as well as the mRNA and protein expression levels of Sirt1 and PGC-1α,were also determined.Meanwhile,renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining.RESULTS Compared with model group,L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification,tail artery SBP,Scr,BUN,UA,Cys-C levels,glomerulosclerosis index score of renal tissue,renal tubular injury score,the percentage of PAS positive area,MDA and 8-OHdG(P＜0.05).Conversely,the contents of SOD and GSH-Px,along with the mRNA and protein expression levels of Sirt1 and PGC-1α,were significantly increased(P＜0.05).Moreover,these improvements were more pronounced in H-pachymic acid group(P＜0.05).Compared with H-pachymic acid group,the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal(P＜0.05).CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats,potentially through activation of the Sirt1/PGC-1α pathway.
朱俊江;林金秤;吴佳健;曾夷;胡君;李敏;刘鸿颖;李金芬
赣南医科大学第三附属医院肾内科,江西 赣州 341000赣南医科大学第三附属医院肾内科,江西 赣州 341000赣南医科大学第三附属医院心内科,江西 赣州 341000赣南医科大学第三附属医院妇产科,江西 赣州 341000赣南医科大学第三附属医院内分泌科,江西 赣州 341000赣南医科大学第三附属医院肾内科,江西 赣州 341000赣南医科大学第三附属医院肾内科,江西 赣州 341000赣州市人民医院产科,江西 赣州 341000
医药卫生
茯苓酸妊娠高血压肾损伤Sirt1/PGC-1α通路
pachymic acidpregnancy induced hypertensionrenal injurySirt1/PGC-1α pathway
《中国药房》 2026 (2)
186-191,6
江西省自然科学基金项目(No.2024BAC205023)江西省卫生健康委科技计划项目(No.202120014)
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