还原型谷胱甘肽对双氯芬酸所致大鼠急性肾损伤的防护作用及其机制研究  

Protective effect of reduced glutathione on acute renal injury induced by diclofenac in rats and its mechanism

作　　者：陈水钫[1] 陈慧[2] 陈雪梅[1] 吕美玲[1] 申九妹[3] 纪凤卿[4] Chen Shuifang;Chen Hui;Chen Xuemei;Lyu Meiling;Shen Jiumei;Ji Fengqing(Department of Pharmacy,Xiamen Hospital of Traditional Chinese Medicine,Fujian Province,Xiamen 361009,China;Department of Nephrology,Xiamen Hospital of Traditional Chinese Medicine,Fujian Province,Xiamen 361009,China;Department of Pathology,Xiamen Hospital of Traditional Chinese Medicine,Fujian Province,Xiamen 361009,China;Department of Clinical Laboratory,Xiamen Hospital of Traditional Chinese Medicine,Fujian Province,Xiamen 361009,China)

机构地区：[1]厦门市中医院药学部,厦门361009 [2]厦门市中医院肾病科,厦门361009 [3]厦门市中医院病理科,厦门361009 [4]厦门市中医院检验科,厦门361009

出　　处：《药物不良反应杂志》2023年第4期223-228,共6页Adverse Drug Reactions Journal

基　　金：厦门市科技计划项目(3502Z20214ZD1163)。

摘　　要：目的探讨还原型谷胱甘肽(GSH)对双氯芬酸诱导大鼠急性肾损伤(AKI)的防护作用及其机制。方法将33只8周龄无特定病原体级雄性SD大鼠按随机数字表法随机分成对照组、模型组和GSH组,每组11只。模型组和GSH组大鼠以双氯芬酸钠溶液(200 mg/kg)灌胃建立AKI模型。建模后30 min,GSH组大鼠用GSH溶液(500 mg/kg)灌胃,对照组和模型组大鼠用等容积0.9%氯化钠注射液灌胃。24 h后采血并分离肾脏,进行肾功能[血尿素氮(BUN)、血清肌酐(Scr)]、肾脏组织病理学以及血清和肾脏组织氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)和炎症细胞因子肿瘤坏死因子(TNF‑α)、白细胞介素6(IL‑6)检查。比较3组大鼠各项检查结果。结果模型组大鼠BUN和Scr明显高于对照组和GSH组[BUN:(14.34±8.47)mmol/L比(7.89±2.20)和(8.46±3.58)mmol/L;Scr:(34.44±6.56)μmol/L比(24.77±9.50)和(29.28±4.33)μmol/L],差异均有统计学意义(均P<0.05)。模型组和GSH组大鼠均可见肾小球和肾小管形态学改变,但GSH组改变程度轻于模型组。GSH组大鼠血清和肾脏组织MDA、TNF‑α和IL‑6水平明显低于模型组[MDA:(9.5±0.2)nmol/ml比(10.2±0.6)nmol/ml,(3.6±0.3)nmol/ml比(4.0±0.2)nmol/ml;TNF‑α:(2.9±2.5)pg/ml比(5.4±3.0)pg/ml,(420.9±40.3)pg/ml比(470.4±31.3)pg/ml;IL‑6:(92.1±34.4)pg/ml比(123.9±16.6)pg/ml,(7547±604)pg/ml比(8047±470)pg/ml],而SOD活性明显高于模型组[(102.8±2.8)U/ml比(99.7±4.1)U/ml,(387.0±12.7)U/ml比(375.9±11.7)U/ml],差异均有统计学意义(均P<0.05)。结论GSH对双氯芬酸所致大鼠急性肾损伤有一定防护作用,其可能机制为抑制氧化应激和炎症反应。Objective To investigate the protective effect of reduced glutathione(GSH)on diclofenac‑induced acute kidney injury(AKI)in rats and its mechanism.Methods Thirty-three male 8‑week‑old specified pathogen‑free SD rats were randomly divided into control,model,and GSH groups(11 rats in each group)according to a random number table method.Diclofenac sodium solution(200 mg/kg)was intragastrically administered to rats in the model group and GSH group to establish the AKI model.Thirty minutes later,rats in the GSH group were treated with intragastric administration of GSH solution(500 mg/kg),while rats in the control and model groups were with 0.9%sodium chloride injection of equal volume.After 24 hours of administration,blood sample was collected and kidneys were isolated.Kidney function[blood urea nitrogen(BUN),serum creatinine(Scr)],kidney histopathology,and serum and kidney tissue oxidative stress indicators such as malondialdehyde(MDA),superoxide dismutase(SOD),and the inflammatory cytokines such as tumor necrosis factor(TNF)‑αand interleukin 6(IL‑6)were examined.The results of each examination results among rats of the 3 groups were compared.Results The BUN and Scr in rats of the model group were significantly higher than those in the control and GSH groups[BUN:(14.34±8.47)mmol/L vs.(7.89±2.20)and(8.46±3.58)mmol/L;Scr:(34.44±6.56)μmol/L vs.(24.77±9.50)and(29.28±4.33)μmol/L,all P<0.05].Glomerular and tubular morphological changes were observed in both model and GSH rats,but the change in rats of GSH group was less severe than that of the model group.The mean levels of MDA,TNF‑α,and IL‑6 in both serum and kidney tissue in rats of GSH group were significantly lower than those of the model group[MDA:(9.5±0.2)nmol/ml vs.(10.2±0.6)nmol/ml,(3.6±0.3)nmol/ml vs.(4.0±0.2)nmol/ml;TNF‑α:(2.9±2.5)pg/ml vs.(5.4±3.0)pg/ml,(420.9±40.3)pg/ml vs.(470.4±31.3)pg/ml;IL‑6:(92.1±34.4)pg/ml vs.(123.9±16.6)pg/ml,(7547±604)pg/ml vs.(8047±470)pg/ml,all P<0.05],while the activity of SOD was significan

关 键 词：谷胱甘肽 双氯芬酸 急性肾损伤 氧化应激 炎症反应 

分 类 号：R692[医药卫生—泌尿科学]