机构地区:[1]江西省南昌大学第一附属医院肾内科,江西南昌330006
出 处:《中药新药与临床药理》2015年第6期759-764,共6页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:江西省卫生厅科技计划项目(20091053)
摘 要:目的探讨黄葵总黄酮对C-BSA慢性肾小球肾炎大鼠的治疗作用以及对肾脏炎症和氧化自由基水平的影响。方法取SD大鼠60只,随机分为5组,每组12只,即正常对照组,模型组,黄葵总黄酮低、中、高剂量组(5,10,15 mg·kg-1)。采用小牛血清白蛋白(C-BSA)诱发慢性肾小球肾炎大鼠模型。对照组和模型组大鼠尾静脉注射等体积的PBS。连续治疗3周,对大鼠24 h尿蛋白定量(24 h UTP)、血肌酐(Scr)和尿素氮(BUN)水平进行分析。3周后观察肾脏组织病理学变化。采用实时荧光定量PCR和ELISA测定白介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)等炎症因子的变化。并测定大鼠血清丙二醛(MDA)、一氧化氮(NO)和超氧化物歧化酶(SOD)活性的变化。结果治疗3周后,黄葵总黄酮低、中、高剂量组大鼠24 h UTP、Scr、BUN水平较模型组明显改善(P<0.05)。黄葵总黄酮低、中、高剂量组,大鼠蛋白尿、血清肌酐和尿素氮水平呈剂量依赖性下降(P<0.05)。病理结果显示,黄葵总黄酮各剂量组大鼠肾小球增大、基底膜增厚、间质和曲管病变随着剂量的增加有不同程度的减轻。黄葵总黄酮各剂量组大鼠肾脏组织中炎症因子IL-1β与TNF-αmRNA和蛋白质水平较模型组明显下降,而且随着药物剂量增加,大鼠肾脏组织中炎症因子IL-1β与TNF-αmRNA和蛋白质水平也逐渐下降。但是高剂量组大鼠肾脏组织中IL-1β与TNF-αmRNA和蛋白质水平略高于对照组(P<0.05)。黄葵总黄酮各剂量组大鼠血清中MDA水平较模型组明显下降,而SOD和NO较模型组显著升高(P<0.05)。结论黄葵总黄酮治疗慢性肾小球肾炎疗效显著,可显著下调肾脏组织炎症因子水平,同时清除机体自由基,有望成为治疗慢性肾小球肾炎的药物。Objective To investigate the therapeutic effect of Huangkui (Radix seu Folium Abelmoschi Moschati) flavonoids on rats with chronic glomerulonephritis induced by calf-bovine serum albumin (C-BSA), and to observe the effect of Huangkui flavonoids (HF) on oxygen free radicals. Methods A total of 60 SD rats were randomized into normal control group, model group, and low-, middle- and high-dose HF groups (5, 10, 15 mg.kg-1), 12 rats in each group. Rat model of chronic glomerular nephritis was induced by C-BSA. Rats in the normal control group and model group were given intravenous injection of equal volume of PBS through the caudal vein. The treatment lasted for 3 weeks.The urine protein, serum creatinine and urea nitrogen levels in rats of the five groups were analyzed. Inflammatory cytokines of interleukin-1β(IL-1β) and tumor necrosis factor alpha(TNF-α) mRNA and protein level were analyzed by real-time fluorescence quantitative PCR and ELISA. Serum activities of malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase(SOD) in rats were also analyzed before and after treatment. At the end of the experiment, the kidney was sliced for the renal pathological observation. Results After treatment for three weeks, urine protein, serum creatinine and urea nitrogen levels in low-, middle- and high-dose HF groups were significantly decreased(P 〈 0.05 compared with those of the model group), and the decrease was in dose-dependent manner(P 〈 0.05). The results of renal pathological observation showed that the glomerulus enlargement, basal membrane thickening, and stroma and tubule affection were reduced with the increase of the dose in HF groups. Inflammatory cytokines of IL-1 β and TNF-αmRNA and protein levels in HF groups were dose-dependently decreased compared with those of the model group(P 〈 0.05), but their levels in high-dose HF group were still higher than the normal control group (P 〈 0.05). Serum MDA level was significantly reduced, but SOD an
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