【摘要】 目的探讨分心木提取物对横纹肌溶解所致急性肾损伤大鼠的防治作用及其可能机制。方法将大鼠随机分成正常对照组、模型组、分心木水和醇提取物180和360 mg/kg各2组,共6组,以设计剂量每日1次灌胃30 d后,采用大鼠双侧后腿注射甘油建立横纹肌溶解急性肾损伤动物模型,于造模后的第24 h和48 h分别观察各组动物的肾功能和肾组织病理变化,并检测血清中抗氧化指标及肿瘤坏死因子-ɑ(TNF-ɑ)水平。结果造模成功后,模型组较正常对照组动物24 h尿量显著减少,血清中肌酐(Cr)、尿素氮(BUN)、TNF-ɑ和丙二醛(MDA)水平显著增高,谷胱甘肽过氧化物酶(GSH-Px)和总超氧化歧化酶(T-SOD)活性显著下降,肾小管出现各种病变,大量蛋白管型形成,管腔完全消失,以上指标随时间推移加剧(P<0.05或P<0.01)。应用分心木醇提取物干预后,与模型组比较,180 mg/kg干预仅能有效增加24 h尿量和降低第48 h的TNF-ɑ和MDA水平,肾脏病变没有随时间而加剧;而360 mg/kg干预则可显著增加24 h尿量并提高GSH-Px和T-SOD活性,同时降低各时点Cr、BUN和MDA水平以及第48 h的TNF-ɑ水平,肾脏病变少于模型组,部分动物肾小管恢复可见狭窄的管腔,以上差异具有统计学意义(P<0.05或P<0.01)。应用分心木水提取物干预后,与模型组比较,180 mg/kg干预各项指标均无明显改善,差异无统计学意义(P>0.05);而360 mg/kg干预可显著增加24 h尿量,提高第48 h的T-SOD活性,并有效降低第48 h的Cr、BUN、TNF-ɑ和MDA水平,同时肾脏病变得到有效改善,但作用强度不及相同剂量醇提取物,以上差异具有统计学意义(P<0.05或P<0.01)。结论分心木提取物360 mg/kg能有效改善横纹肌溶解导致的急性肾功能损伤,保护累及的肾组织,且醇提取物效果优于水提取物。其作用机制可能与抑制炎症反应,发挥抗氧化作用有关。更多还原

【Abstract】 Objective To investigate the protective effect and possible mechanism of Diaphragma Juglandis Fructus(DJF)extracts on the rhabdomyolysis-induced acute kidney injury(AKI)in Sprague-Dawley(SD)rats.Methods Sixty male SD rats were randomly divided into 6 groups:normal control group,model group as well as the four test groups treated with 180 mg/kg and 360 mg/kg water extract or alcohol extract of DJF.The rats were orally administered once a day by gavage with the designed concentration of test substances or distilled water(for controls)for 30 days.After the last drug administration,all rats except for those in the normal control group were subjected to the intramuscular injection of 50% glycerol to both hind limbs to create the rat model of rhabdomyolysis-induced AKI.The renal function and kidney histopathology were then examined and the serum level of tumor necrosis factor-alpha(TNF-ɑ)and antioxidant indicators were detected at 24 and 48 hours after the glycerol injection.Results Compared with the normal control group,the urine volume for 24 h as well as the serum glutathione peroxidase(GSH-Px)and total superoxide dismutase(TSOD)activities were significantly decreased,while the serum creatinine(Cr),blood urea nitrogen(BUN),TNF-ɑ and malondialdehyde(MDA)level was significantly increased in the model group(P<0.05 or P<0.01).Meanwhile,various lesions in renal tubules appeared in the model group,including plenty of protein casts and complete disappearance of the lumen,etc.Compared with the model group,the intervention with the 180 mg/kg DJF alcohol extract effectively increased the urine volume for 24 h and reduced the serum MDA and TNF-α level on the 48 h.Furthermore,the administration of 360 mg/kg DJF alcohol extract not only effectively increased the urine volume for 24 h, enhanced the serum GSH-Px and T-SOD activity, and decreased the serum Cr,BUN,MDA and TNF-ɑ(48 h)level,but also significantly improved the rhabdomyolysis-induced AKI in rat(P<0.05 or P<0.01).On the other hand, the administration of 180 mg/kg DJF water extract did not effectively improve any related parameters(P>0.05).However,the intervention with the 360 mg/kg DJF water extract significantly increased the urine volume for 24 h,enhanced the serum T-SOD activity on the 48 h,and decreased the serum Cr,BUN,MDA and TNF-α level on the 48 h(P<0.05 or P<0.01).Conclusion sBoth the 360 mg/kg DJF alcohol and water extracts could effectively protect the rhabdomyolysis-induced AKI,which caused by glycerol in SD rats,and the effect of the alcohol extract was better than that of the water extract.The possible mechanism is likely related to the inhibition of inflammation and a positive role in antioxidation.更多还原