吴茱萸碱通过抑制氧化应激反应对肾草酸钙结石模型大鼠肾功能的影响

Effect of Evodiamine by Inhibiting Oxidative Stress on Kidney Function in Rat Modelsof Renal Calcium Oxalate Stones

目的:观察吴茱萸碱(EVO)通过抑制氧化应激反应对肾草酸钙结石模型大鼠肾功能的影响。方法:从50只SPF级SD雄性大鼠中随机选出10只大鼠作为空白组,其余大鼠通过灌胃1.25%乙二醇+1%氯化铵混合液构建草酸钙结石模型,造模成功后随机分为模型组、L-EVO组、H-EVO组以及阳性组,每组10只。L-EVO组、H-EVO组分别通过腹腔注射40 mg/kg和80 mg/kg的EVO,阳性组灌胃20 mg/kg的葛根素,每天1次,连续处理4周,空白组、模型组给予等量0.9%氯化钠溶液。检测大鼠尿液以及血清生化指标;HE染色检测肾组织病理变化;Pizzolato染色检测草酸钙晶体沉积。结果:组织病理学检查显示,空白组大鼠肾组织染色清晰,均无草酸钙沉积、肾小管变性、坏死或炎症,未见草酸钙晶体沉积。与空白组比较,模型组发现了广泛的肾小管内草酸晶体沉积,严重的肾小管变性、坏死,炎性细胞浸润到肾间质以及肾小管囊肿形成。与模型组比较,L-EVO组、H-EVO组、阳性组肾脏结构明显改善。与空白组比较,模型组草酸钙晶体数量、钙、草酸盐、磷酸盐、尿素氮、尿素、尿酸、丙二醛(MDA)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)、草酸钙晶体沉积升高(P<0.05),镁、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量降低(P<0.05)。与模型组比较,L-EVO组、H-EVO组、阳性组草酸钙晶体数量、钙、草酸盐、磷酸盐、尿素氮、尿素、尿酸、MDA、TNF-α、IL-1β、草酸钙晶体沉积含量降低(P<0.05),镁、SOD、GSH含量升高(P<0.05)。与L-EVO组比较,H-EVO组草酸钙晶体数量、钙、草酸盐、磷酸盐、尿素氮、尿素、尿酸、MDA、TNF-α、IL-1β、草酸钙晶体沉积含量减少(P<0.05),镁、SOD、GSH含量增加(P<0.05)。结论:EVO可通过抑制氧化应激反应改善肾草酸钙结石模型大鼠肾功能。

Objective:To observe the effect of Evodiamine(EVO)by inhibiting oxidative stress on kidney function in rat models of renal calcium oxalate stones.Methods:A total of 10 rats were randomly selected from 50 SPF SD male rats as the blank group,and the rest rats were used to establish the rat models ofrenal calcium oxalate stones by intragastrical administration of 1.25% ethylene glycol + 1% ammoniumchloride mixture. After successful modeling, the above rat models were randomly divided into the modelgroup , the L-EVO group , the H-EVO group and the positive group , with 10 rats in each group. TheL-EVO group and the H-EVO group were intraperitoneally injected with 40 mg/kg and 80 mg/kg EVO,respectively. The positive group was intragastrically administered with 20 mg/kg Puerarin once a day. All thegroups were treated for four weeks. The blank group and the model group were given the same amount ofnormal saline. The urine and serum biochemical indexes of rats were detected;HE staining was used todetect the pathological changes of renal tissue;the deposition of calcium oxalate crystals was detected byPizzolato staining. Results:Histopathological examination showed that the staining of renal tissue of rats inthe blank group was clear, and there was no calcium oxalate deposition, renal tubular degeneration,necrosis or inflammation, and calcium oxalate crystal deposition. Compared with the blank group, themodel group found extensive oxalate crystal deposition in the renal tubules, severe renal tubulardegeneration and necrosis,inflammatory cell infiltration into the renal interstitium and the formation of renaltubular cyst. The renal structure in the L-EVO group, the H-EVO group and the positive group wassignificantly improved when compared with that in the model group. The number of calcium oxalate crystals,and the levels of calcium, oxalate, phosphate, urea nitrogen, urea, uric acid, MDA, TNF- α, IL-1βand calcium oxalate crystal deposition in the model group were elevated when compared with those in theblank group (P<0.05), and the contents of magnesium, SOD and GSH were down-regulated (P<0.05).Compared with those in the model group, the number of calcium oxalate crystals, and the levels ofcalcium,oxalate,phosphate,urea nitrogen,urea,uric acid,MDA,TNF-α,IL-1β and calcium oxalatecrystal deposition in the L-EVO group,H-EVO group and positive group were respectively dwindled (P<0.05),and the contents of magnesium,SOD and GSH were up-regulated (P<0.05). Compared with thosein the L-EVO group, the number of calcium oxalate crystals, and the levels of calcium, oxalate,phosphate,urea nitrogen,urea,uric acid,MDA and TNF-α,IL-1β and calcium oxalate crystal depositionin the H-EVO group were reduced (P<0.05), and the contents of magnesium, SOD and GSH wereelevated (P<0.05). Conclusion:EVO can improve the kidney function in rat models of renal calcium oxalatestones by inhibiting oxidative stress.