| 应俊杰,徐毅,雷樟明,等.搜风解毒汤对顺铂诱导的急性肾损伤小鼠肾脏氧化应激和自噬的影响[J].浙江中医药大学学报,2024,48(9):1093-1101. |
| 搜风解毒汤对顺铂诱导的急性肾损伤小鼠肾脏氧化应激和自噬的影响 |
| Effect of Soufeng Jiedu Decoction on Renal Oxidative Stress and Autophagy in Mice with Cisplatin-induced Acute Kidney Injury |
| DOI：10.16466/j.issn1005-5509.2024.09.005 |
| 中文关键词: 搜风解毒汤 顺铂 急性肾损伤 氧化应激 自噬 NRF2 AMPK |
| 英文关键词: Soufeng Jiedu Decoction cisplatin acute kidney injury oxidative stress autophagy NRF2 AMPK |
| 基金项目:浙江省中医药科技计划项目(2020ZA120)；衢州市科技计划竞争性分配项目(2023K120) |
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| 中文摘要: |
| [目的] 探讨搜风解毒汤干预顺铂诱导的急性肾损伤的作用及机制。[方法] 40只C57BL/6J小鼠随机分为5组，每组8只，对照组和模型组以蒸馏水灌胃，阳性对照组以泼尼松龙5 mg/(kg·d)灌胃，搜风解毒汤低、高剂量组分别以搜风解毒汤300、500 mg/(kg·d)灌胃，连续给药10 d。给药第7天，模型组，阳性对照组，搜风解毒汤低、高剂量组分别单次腹腔注射顺铂20 mg·kg-1，对照组给予同等剂量0.9%氯化钠溶液。采用生化法检测各组小鼠血尿素氮(blood urea nitrogen，BUN)、血清肌酐(serum creatinine，SCr)，肾组织丙二醛(malondialdehyde，MDA)水平及超氧化物歧化酶(superoxide dismutase，SOD)和过氧化氢酶(catalase，CAT)活性；苏木精-伊红(hematoxylin-eosin，HE)染色观察肾组织病理学形态；实时定量聚合酶链式反应(Real time-quantitative polymerase chain reaction，RT-qPCR)检测肾脏肾损伤分子-1(kidney injury molecule-1，Kim-1)、中性粒细胞明胶酶相关脂质运载蛋白(neutropil gelatinase-associated lipocalin，Ngal)、醌氧化还原酶1(NADPH: quinone oxidoreductase 1，Nqo1)和谷氨酸半胱氨酸连接酶(glutamate cysteine ligase，Gclm)基因表达；免疫印迹法检测核因子红细胞2相关因子2(nuclear factor erythroid 2-related factor 2，NRF2)、血红素加氧酶-1(heme oxygenase-1，HO-1)、p62、微管相关蛋白轻链3(microtubule-associated protein light chain 3，LC3B)、磷酸化AMP依赖的蛋白激酶(phosphorylated-AMP-activated protein kinase，p-AMPK)等蛋白表达情况。[结果] 与对照组比较，模型组小鼠BUN、SCr水平和Kim-1、Ngal基因表达显著升高(P<0.01)；肾脏损伤严重，表现为肾小管变性、水肿、坏死、囊性扩张伴局灶性出血；MDA水平显著升高，CAT和SOD活性显著降低(P<0.01)；肾脏Nqo1和Gclm基因表达升高，NRF2、HO-1、LC3B蛋白表达水平显著升高，p62、p-AMPK蛋白表达显著降低(P<0.01)。与模型组比较，搜风解毒汤能够显著降低小鼠BUN、SCr水平，抑制肾脏Kim-1、Ngal基因表达；减轻急性肾损伤小鼠肾组织病变；降低肾脏MDA水平，提高CAT和SOD活性；促进Nqo1和Gclm基因以及NRF2、HO-1、LC3B、p-AMPK蛋白表达，抑制p62蛋白表达(P<0.01)。[结论] 搜风解毒汤能够有效缓解顺铂诱导的急性肾损伤，其机制可能与抑制肾脏氧化应激和促进自噬有关。 |
| 英文摘要: |
| [Objective] To investigate the effect and mechanism of Soufeng Jiedu Decoction on cisplatin-induced acute kidney injury. [Methods] Forty C57BL/6J mice were randomly divided into 5 ?groups，8 mice in each group: control group and model group were gavaged with distilled water， positive control group was gavaged with prednisolone 5 mg/(kg·d)， Soufeng Jiedu Decoction low and high dose groups were gavaged with Soufeng Jiedu Decoction 300 and 500 mg/(kg·d) respectively. These drugs were administered continuously for 10 days. On the 7th day of administration， mice in model group， positive control group， Soufeng Jiedu Decoction low dose group， and Soufeng Jiedu Decoction high dose group were intraperitoneally injected with 20 mg·kg-1 cisplatin， while the control group received an equivalent volume of 0.9% sodium chloride solution. Biochemical approaches were utilized to measure the levels of blood urea nitrogen(BUN)， serum creatinine(SCr)， malondialdehyde(MDA)， and the activity of superoxide dismutase(SOD) and catalase(CAT). Kidney tissue pathological morphology was assessed using hematoxylin-eosin(HE) staining in all groups. Real time-quantitative polymerase chain reaction(RT-qPCR) was employed to determine the gene expressions of kidney injury molecule-1(Kim-1)， neutrophil gelatinase-associated lipocalin(Ngal)， quinone oxidoreductase 1(Nqo1) and glutamate cysteine ligase(Gclm) in the kidney of mice. Western blot analysis was conducted to evaluate the protein expressions of nuclear factor erythroid 2-related factor 2(NRF2)， heme oxygenase-1(HO-1)， p62， microtubule-associated protein light chain 3(LC3B) and phosphorylated-AMP-activated protein kinase(p-AMPK). [Results] Compared with control group， model group exhibited a significant increase in levels of BUN and SCr， as well as upregulation of Kim-1 and Ngal gene expression(P<0.01). Notably， severe kidney injury was observed in model group， characterized by tubular degeneration， edema， necrosis， cystic dilatation with focal hemorrhage. Moreover， model group exhibited a significant increase in MDA levels， accompanied by a notable decrease in CAT and SOD activities(P<0.01). On the other hand， model group displayed elevated expressions of renal Nqo1 and Gclm genes， as well as increased protein expressions of NRF2， HO-1， and LC3B， while the protein expressions of p62 and p-AMPK were significantly reduced(P<0.01). Compared with model group， treatment with Soufeng Jiedu Decoction resulted in a significant reduction in BUN and SCr levels， as well as suppression of Kim-1 and Ngal gene expression in the kidney of mice. Furthermore， Soufeng Jiedu Decoction ameliorated acute kidney injury-associated renal tissue lesions. Treatment with Soufeng Jiedu Decoction also led to a decrease in MDA levels， and an increase in CAT and SOD activities within the kidney. Additionally， Soufeng Jiedu Decoction promoted the expression of Nqo1 and Gclm genes， as well as the protein expressions of NRF2， HO-1， LC3B and p-AMPK， while inhibiting the expression of p62 protein(P<0.01). [Conclusion] Soufeng Jiedu Decoction effectively alleviates cisplatin-induced acute kidney injury possibly by inhibiting oxidative stress and promoting autophagy in the kidney. |
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