摘要
目的探讨栀子苷(GPO)调节腺苷酸活化蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)通路对阿霉素诱导的肾病综合征(NS)大鼠肾损伤的影响。方法将SD大鼠分为对照组(CK组)、Model组、低剂量GPO组(GPO-L组,25 mg/kg)、高剂量GPO组(GPO-H组,100 mg/kg)、醋酸泼尼松组(PA组,6.3 mg/kg)、GPO-H+compound C(AMPK抑制剂)组(100 mg/kg+0.2 mg/kg),每组12只。除CK组外,其他组均需构建NS大鼠模型。建模成功后,进行给药处理,给药每天1次,持续8周。检测大鼠24 h尿蛋白(24 h UP)及大鼠血清中肌酐(Scr)、尿素氮(BUN)、甘油三酯(TG)、总胆固醇(TC)水平。HE染色检测大鼠肾组织病理损伤;检测大鼠肾组织中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、干扰素-γ(IFN-γ)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、活性氧(ROS)水平;TUNEL染色检测肾细胞凋亡;Western blot检测肾组织中p-AMPK、SIRT1蛋白表达。结果与CK组比较,Model组大鼠肾组织病理损伤严重,24 h UP[(82.32±7.31)mg vs.(358.85±34.26)mg]、Scr[(42.28±3.67)mmol/L vs.(163.34±14.45)mmol/L]、BUN[(3.02±0.21)mmol/L vs.(9.73±1.02)mmol/L]、TG[(0.31±0.02)mmol/L vs.(0.99±0.08)mmol/L]、TC[(2.25±0.64)mmol/L vs.(8.55±1.04)mmol/L]、TNF-α[(31.36±3.23)pg/mL vs.(256.67±22.33)pg/mL]、IL-6[(52.35±4.67)pg/mL vs.(148.72±11.24)pg/mL]、IFN-γ[(89.82±6.42)pg/mL vs.(326.59±29.87)pg/mL]、ROS[(267.75±22.35)ng/L vs.(492.79±46.63)ng/L]水平及肾细胞凋亡率[(4.26±0.33)%vs.(39.94±3.15)%]升高,SOD[(345.52±32.27)U/mL vs.(126.58±11.42)U/mL]、GSH-Px[(321.68±31.12)U vs.(156.54±13.35)U]水平及p-AMPK、SIRT1蛋白表达降低,差异有统计学意义(P均<0.05);与Model组比较,GPO-L组、GPO-H组、PA组对应指标变化趋势与上述相反,差异有统计学意义(P均<0.05)。Compound C减弱了高剂量GPO对NS大鼠肾损伤的改善作用。结论GPO可能通过激活AMPK/SIRT1信号通路改善阿霉素诱导的NS大鼠肾损伤。
Objective To investigate the impacts of geniposide(GPO)on renal injury in rats with adriamycin-induced nephrotic syndrome(NS)by regulating adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(SIRT1)pathway.Methods SD rats were grouped into control group,model group,low-dose GPO group(GPO-L group,25 mg/kg),high-dose GPO group(GPO-H group,100 mg/kg),prednisone acetate group(PA group,6.3 mg/kg),GPO-H+compound C(AMPK inhibitor)group(100 mg/kg+0.2 mg/kg),12 animals in each group.Except for the CK group,constructed NS model rats were used for all other groups.Treatment was performed once a day for 8 weeks.The levels of serum creatinine(Scr),blood urea nitrogen(BUN),triglyceride(TG),total cholesterol(TC)and 24 h urinary protein(24 h UP)in rats were measured.HE staining was used to detect the pathological damage of rat kidney tissue.The levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interferon-γ(IFN-γ),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and reactive oxygen species(ROS)in rat kidney tissue were measured.TUNEL staining was used to detect renal cell apoptosis.Western blot was used to detect the expression of p-AMPK,SIRT1 proteins in rat kidney tissue.Results Compared with the CK group,the model group had severe renal tissue pathological damage,and the levels of 24 h UP(82.32±7.31)mg vs.(358.85±34.26)mg,Scr(42.28±3.67)mmol/L vs.(163.34±14.45)mmol/L,BUN(3.02±0.21)mmol/L vs.(9.73±1.02)mmol/L,TG(0.31±0.02)mmol/L vs.(0.99±0.08)mmol/L,TC(2.25±0.64)mmol/L vs.(8.55±1.04)mmol/L,TNF-α(31.36±3.23)pg/mL vs.(256.67±22.33)pg/mL,IL-6(52.35±4.67)pg/mL vs.(148.72±11.24)pg/mL,IFN-γ(89.82±6.42)pg/mL vs.(326.59±29.87)pg/mL,ROS(267.75±22.35)ng/L vs.(492.79±46.63)ng/L and renal cell apoptosis(4.26±0.33)%vs.(39.94±3.15)%increased,the levels of SOD(345.52±32.27)U/mL vs.(126.58±11.42)U/mL,GSH-Px(321.68±31.12)U vs.(156.54±13.35)U,and the protein expressions p-AMPK and SIRT1 decreased(all P<0.05);compared with the model group,the corresponding indicators in the GPO-L group,GPO-H group and PA group had the opposite trends(all P<0.05);compound C attenuated the ameliorating effect of high-dose GPO on renal injury in NS rats.Conclusion GPO might ameliorate adriamycin-induced renal injury in NS rats by activating the AMPK/SIRT1 signaling pathway.
作者
韩博
于敏
熊锡山
HAN Bo;YU Min;XIONG Xi-shan(Department of Nephrology,Fifth Medical Center,Chinese People's Liberation Army General Hospital,Beijing 100071,China;Department of Nephrology,Suzhou Hospital Affiliated to Anhui Medical University,Suzhou,Anhui 234000,China)
出处
《热带医学杂志》
CAS
2022年第10期1345-1350,1463,共7页
Journal of Tropical Medicine
基金
安徽省高校自然科学研究项目(KJ2021A0346)
关键词
栀子苷
腺苷酸活化蛋白激酶/沉默信息调节因子1
肾病综合征
氧化应激
Geniposide
Adenosine monophosphate activated protein kinase/silent information regulator 1
Nephrotic syndrome
Oxidative stress
作者简介
韩博(1978-),男,学士,主治医师,主要从事血液净化、汞中毒相关性肾病、肿瘤相关性肾病方面研究;通信作者:熊锡山,E-mail:sunghai@163.com
