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成都大学附属医院急诊科,成都 610081
Published:15 June 2024,
Received:28 December 2023,
Revised:11 April 2024,
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申翔,徐尚刚,黄洋辉等.薯蓣皂苷对脓毒症大鼠肾损伤的影响及机制 Δ[J].中国药房,2024,35(11):1334-1338.
SHEN Xiang,XU Shanggang,HUANG Yanghui,et al.Effect and mechanism of dioscin on renal injury in septic rats[J].ZHONGGUO YAOFANG,2024,35(11):1334-1338.
申翔,徐尚刚,黄洋辉等.薯蓣皂苷对脓毒症大鼠肾损伤的影响及机制 Δ[J].中国药房,2024,35(11):1334-1338. DOI: 10.6039/j.issn.1001-0408.2024.11.09.
SHEN Xiang,XU Shanggang,HUANG Yanghui,et al.Effect and mechanism of dioscin on renal injury in septic rats[J].ZHONGGUO YAOFANG,2024,35(11):1334-1338. DOI: 10.6039/j.issn.1001-0408.2024.11.09.
目的
2
探究薯蓣皂苷对脓毒症大鼠肾损伤的影响及可能机制。
方法
2
采用盲肠结扎和穿刺法建立脓毒症大鼠模型。将建模成功的60只大鼠按照随机数字表法分为模型组(0.5%羧甲基纤维素钠溶液),薯蓣皂苷低、中、高剂量组(30、60、120 mg/kg)和地塞米松组(阳性对照,10 mg/kg),每组12只;另取12只大鼠作为假手术组(0.5%羧甲基纤维素钠溶液)。造模15 min后,各组大鼠尾静脉注射给药/0.5%羧甲基纤维素钠溶液。给药24 h后,检测大鼠血清中肌酐(Cr)、尿素氮(BUN)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子1(KIM-1)、白细胞介素6(IL-6)、IL-1β、肿瘤坏死因子α(TNF-α)水平以及肾组织中丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性和核因子E2相关因子2(Nrf2)、血红素加氧酶1(HO-1)、NOD样受体蛋白3(NLRP3)表达量,并观察肾组织病理形态学变化。
结果
2
与模型组比较,薯蓣皂苷低、中、高剂量组大鼠肾组织病理损伤明显改善,血清中Cr、BUN、NGAL、KIM-1、IL-6、IL-1β、TNF-α水平和肾组织中MDA水平、NLRP3蛋白表达量均显著降低(
P
<0.05),肾组织中SOD活性和Nrf2、HO-1蛋白表达量均显著升高(
P
<0.05),且薯蓣皂苷的作用具有剂量依赖性(
P
<0.05);薯蓣皂苷高剂量组和地塞米松组大鼠肾组织病理损伤情况相似,上述指标水平差异均无统计学意义(
P
>0.05)。
结论
2
薯蓣皂苷可能是通过激活Nrf2/HO-1信号通路抑制NLRP3炎性小体,实现对炎症因子表达和氧化应激的抑制,从而发挥对脓毒症肾损伤的保护作用。
OBJECTIVE
2
To investigate the effect of dioscin on renal injury in septic rats and its possible mechanism.
METHODS
2
The septic rat model was induced by using cecal ligation and puncture. Sixty model rats were randomly divided into model group (0.5% sodium carboxymethyl cellulose solution), dioscin low-dose, medium-dose and high-dose groups (30, 60, 120 mg/kg) and dexamethasone group (positive control, 10 mg/kg), with 12 rats per group; another 12 rats were selected as the sham operation group (0.5% sodium carboxymethyl cellulose solution). After 15 minutes of modeling, rats in each group were injected with medicine/0.5% sodium carboxymethyl cellulose solution via the tail vein. Twenty-four hours after administration, the levels of creatinine (Cr), blood urea nitrogen (BUN), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin 6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) in serum and malondialdehyde (MDA) in renal tissue, superoxide dismutase (SOD) activity and the protein expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NOD-like receptor protein 3 (NLRP3) were detected; renal histomorphology was observed.
RESULTS
2
Compared with model group, pathological injury of renal tissue was improved significantly in dioscin low-dose, medium-dose and high-dose groups; the levels of Cr, BUN, NGAL, KIM-1, IL-6, IL-1β and TNF-α in serum, MDA level and protein expression of NLRP3 in renal tissue were decreased significantly (
P
<0.05); SOD activity in renal tissue, protein expressions of Nrf2 and HO-1 were increased significantly (
P
<0.05), in a dose-dependent manner (
P
<0.05). The pathological damage of renal tissue in the dioscin high-dose group was similar to dexamethasone group, and there was no statistically sig
nificant difference in the levels of the above indicators (
P
>0.05).
CONCLUSIONS
2
Dioscin can activate the Nrf2/HO-1 signaling pathway to inhibit NLRP3 inflammasome, and realize the inhibition of inflammatory factors and oxidative stress, so as to protect the kidney injury in sepsis.
薯蓣皂苷Nrf2/HO-1信号通路NLRP3炎性小体脓毒症肾损伤
Nrf2/HO-1 signaling pathwayNOD-like receptor protein 3 inflammasomesepsisrenal injury
ZARBOCK A,NADIM M K,PICKKERS P,et al. Sepsis-associated acute kidney injury:consensus report of the 28th Acute Disease Quality Initiative Workgroup[J]. Nat Rev Nephrol,2023,19(6):401-417.
陈彬彬,陈丹,戴爱国. 薯蓣皂苷减轻脂多糖诱导的急性肺损伤中的炎症反应、氧化应激和Th17/Treg细胞失平衡[J]. 中国组织化学与细胞化学杂志,2022,31(5):461-467.
CHEN B B,CHEN D,DAI A G. Dioscin alleviates inflammatory response,oxidative stress and Th17/Treg cell imbalance in lipopolysaccharide induced acute lung injury[J]. Chin J Histochem Cytochem,2022,31(5):461-467.
刘鹏,王晨,王昀,等. 薯蓣皂苷抑制NF-κB信号通路改善尿酸诱导的肾小管上皮细胞炎性损伤的机制研究[J]. 中国临床药理学与治疗学,2022,27(10):1099-1105.
LIU P,WANG C,WANG Y,et al. Dioscin attenuates inflammatory injury in uric acid-induced renal tubular epithelial cells by suppression of NF-κB signaling pathway[J]. Chin J Clin Pharmacol Ther,2022,27(10):1099-1105.
王爽,金圣子,刘云. 薯蓣皂苷对顺铂诱导急性肾损伤模型大鼠的保护作用[J]. 中国兽医科学,2022,52(9):1199-1206.
WANG S,JIN S Z,LIU Y. Protective effect of dioscin on cisplatin-induced acute kidney injury model in rat[J]. Chin Vet Sci,2022,52(9):1199-1206.
YANG R,CHEN W,LU Y,et al. Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism[J]. Sci Rep,2017,7:40035.
SEDIGHI M,BALUCHNEJADMOJARAD T,AFSHIN-MAJD S,et al. Anti-aging klotho protects SH-SY5Y cells against amyloid β1-42 neurotoxicity:involvement of Wnt1/pCrEB/Nrf2/HO-1 signaling[J]. J Mol Neurosci,2021,71(1):19-27.
GAO Z M,SUI J D,FAN R,et al. Emodin protects against acute pancreatitis-associated lung injury by inhibi- ting NLRP3 inflammasome activation via Nrf2/HO-1 signaling[J]. Drug Des Devel Ther,2020,14:1971-1982.
RiTTIRSCH D,HUBER-LANG M S,FLIERL M A, et al. Immunodesign of experimental sepsis by cecal ligation and puncture[J]. Nat Protoc,2009,4(1):31-36.
楼屹,朱之青,谢莉莉,等. 电针“足三里”对脓毒症大鼠肠黏膜免疫屏障的影响及机制研究[J]. 针刺研究,2022,47(5):386-392.
LOU Y,ZHU Z Q,XIE L L,et al. Study on the effect and machanism of electroacupuncture at “Zusanli” on the immune barrier of intestinal mucosa in sepsis rats[J]. Acupunct Res,2022,47(5):386-392.
武豪杰,张明辉,洪成智. 薯蓣皂苷对滑膜炎大鼠症状的改善作用和对TLR2-NF-κB信号通路的调节作用及其机制[J]. 吉林大学学报(医学版),2021,47(4):943-950.
WU H J,ZHANG M H,HONG C Z. Improvement effect of diosgenin on symptoms of synovitis rats and its regulatory effect on TLR2-NF-κB signaling pathway and mechanism[J]. J Jilin Univ Med Ed,2021,47(4):943-950.
熊玮,彭斌,高智. 松果菊苷对尿毒症大鼠肾损伤的影响及机制[J]. 中国药房,2024,35(2):198-203.
XIONG W,PENG B,GAO Z. Effects of echinacoside on renal injury in uremia rats and its mechanism[J]. China Pharm,2024,35(2):198-203.
ALMAGHRABI S Y. Apigenin ameliorates hypercho- lesterolemic-induced kidney injury via modulating renal KIM-1,Fn1,and Nrf2 signaling pathways[J]. Eur Rev Med Pharmacol Sci,2023,27(3):1155-1169.
王其政,林小飞,朱红利. 地塞米松联合注射用头孢哌酮钠舒巴坦钠对儿童脓毒症的疗效及对血清PCT、Presepsin及NT-proBNP的影响[J]. 药物评价研究,2022,45(1):118-123.
WANG Q Z,LIN X F,ZHU H L. Influences of dexamethasone combined with cefoperazone and sulbactam on efficacy of sepsis in children and serum PCT,presepsin and NT-proBNP[J]. Drug Eval Res,2022,45(1):118-123.
PENG Y Q,LI Y,LI H,et al. Shikonin attenuates kidney tubular epithelial cells apoptosis,oxidative stress,and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model[J]. Drug Dev Res,2022,83(5):1111-1124.
CHOI Y H. Activation of Nrf2/HO-1 antioxidant signaling correlates with the preventive effect of loganin on oxidative injury in ARPE-19 human retinal pigment epithelial cells[J]. Genes Genomics,2023,45(3):271-284.
WANG S H,TSAI K L,CHOU W C,et al. Quercetin mitigates cisplatin-induced oxidative damage and apoptosis in cardiomyocytes through Nrf2/HO-1 signaling pathway[J]. Am J Chin Med,2022,50(5):1281-1298.
CAI Y J,LI X L,TAN X Y,et al. Vitamin D suppresses ferroptosis and protects against neonatal hypoxic-ischemic encephalopathy by activating the Nrf2/HO-1 pathway[J]. Transl Pediatr,2022,11(10):1633-1644.
ZHANG J,WANG C S,KANG K,et al. Loganin atte- nuates septic acute renal injury with the participation of AKT and Nrf2/HO-1 signaling pathways[J]. Drug Des Devel Ther,2021,15:501-513.
LI N,XIONG R,HE R Y,et al. Mangiferin mitigates lipopolysaccharide-induced lung injury by inhibiting NLRP3 inflammasome activation[J]. J Inflamm Res,2021,14:2289-2300.
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