目的 观察木香烃内酯对糖尿病大鼠肾脏损伤的保护作用。方法 70只雄性SD大鼠,正常组12只给予普通饲料喂养,其余给予高脂高糖饮食喂养8周后,以鼠尾静脉注射STZ方法建立糖尿病大鼠模型,并随机分为糖尿病组、胰岛素组、木香烃内酯低剂量组(10 mg)和高剂量组(20 mg)。给药后每周观察各组大鼠一般情况,测量体重、血糖。药物干预8周后,留取血清检测肾功能、SOD、GSH和MDA含量;肾脏组织切片行HE染色;ELISA法测定肾脏组织IL-6、TNF-α的水平;Western-blot法检测各组肾脏组织Nrf2及其下游信号分子HO-1, NF-кB信号通路相关分子NF-кB p65、IKKβ的蛋白表达水平。结果 木香烃内酯治疗组大鼠血糖及肾功能指标较糖尿病组明显下降,肾脏病变显著改善,血清抗氧化指标SOD、GSH较糖尿病组明显升高(P<0.05),氧化应激产物MDA明显降低。肾脏组织IL-6、TNF-α水平较糖尿病组显著降低(P<0.05),Nrf2、HO-1蛋白表达增加(P<0.05),NF-кB p65、IKKβ蛋白表达减少(P<0.05);木香烃内酯高剂量组GSH水平高于低剂量组,IL-6低于低剂量组(P<0.01),其余指标均无统计学差异。结论 木香烃内酯对糖尿病大鼠肾脏损伤具有显著保护作用,可能是通过上调Nrf2表达增强机体抗氧化能力,同时抑制NF-кB炎症通路发挥其保护作用。
Abstract
Objective To investigate the protective effect of costunolide on kidneys in diabetic rats.Methods Twelve male SD rats (chosen from 70 rats) in the control group were fed with normal diet. The other 58 rats were injected with STZ via tail vein after fed with high-sugar and high-fat diet for 8 weeks. Then, these rats were randomly divided into diabetic model group, insulin group, costunolide low dosage group (10 mg) and costunolide high dosage group (20 mg). The general situation, body weight and blood glucose of rats were measured every week after administration. Drug intervention treatment was performed for 8 weeks. Then serum was collected to measure renal function, superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) content. Kidneys were embedded for pathological section with hematoxylin and eosin staining; renal inflammatory cytokines IL-6 and TNF-α expression were detected by ELISA; western blot was used to detect the protein content of Nrf2 and its downstream signaling molecules of HO-1, NF-кB p65signaling pathway related molecules in renal tissue.Results Blood glucose and renal function were significantly better than those in the diabetic group after costunolide treatment. Morphologic observation showed that rat kidney lesion was significantly improved in costunolide treatment group. Serum antioxidant index in costunolide treatment group significantly improved compared with the diabetic group (P<0.05), IL-6 and TNF-α expression were lower than thatof diabetic group (P<0.05). Protein expression of Nrf2, HO-1 increased and NF-кB p65, IKKβ decreased in Costunolide treatment group than that of diabetic group by Western blot(P<0.05). Compared with different CS dose groups, GSH level was higher than CS low dose group and IL-6 was significantly lower than CS low dose group (P<0.01), while the other indicators were not statistically significant.Conclusions Costunolide can significantly protect kidney lesion in diabetic rats, which may be done through upregulating Nrf2 enhanced antioxidant capacity and suppressing the NF-кB inflammatory pathways.
关键词
木香烃内酯 /
糖尿病肾脏疾病 /
抗氧化 /
Nrf2 /
NF-кB
Key words
costunolide /
diabetic kidney disease /
anti-oxidation /
NRf2 /
NF-кB
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