山东医药2017，Vol.57Issue(46)：7-11,5.DOI:10.3969/j.issn.1002-266X.2017.46.002
普罗布考联合山莨菪碱对糖尿病大鼠对比剂肾损伤的影响
Effect of probucol combined with anisodamine on contrast-induced nephropathy in diabetic rats
摘要
Abstract
Objective To explore the synergistic effect of probucol combined with anisodamine on contrast-induced nephropathy (CIN)in diabetic rats. Methods Totally 130 rats were selected to make the models of diabetic rats. The di-abetic rat models were randomly divided into the model group,probucol group,anisodamine group,and the combination group (probucol combined with anisodamine),with 21 rats in each group. In addition,10 normal rats were selected as the control group. After 9-week feeding,the diabetic rats in the probucol group and the combination group received intragastric administration of probucol (500 mg/ kg)for 6 d. On the eighth day,rats in the anisodamine group and combination group were injected with anisodamine 100 μg/ 100g intraperitoneally before the preparation of CIN model. After 15 min,all dia-betic rats were injected with urografin 0. 8 mL/ 100 g intravenously to prepare the CIN models. One hour later,rats in the anisodamine group and combination group were given anisodamine 100 μg/ 100 g intraperitoneally for 7 times. The coomassie brilliant blue (CBB)was used to determine the urinary protein before and after injection with contrast medium 24 h. Blood samples were taken from the inner canthus vein for measuring the serum BUN and Scr levels. After weighed,the left and right kidneys of all rats were also weighed for calculating the renal index. Pathological changes of kidneys were ob-served by HE staining. The renal tissues were homogenized for testing nitric oxide (NO),nitric oxide synthase (NOS), superoxide dismutase (SOD),malondialdehyde (MDA)and total antioxidant capacity (T-AOC). The expression levels of B cell lymphoma/ leukemia-2 gene (Bcl-2)and Bcl-2-related X protein (Bax)mRNA were detected by fluorescent quanti-tative PCR. Results ①The levels of BUN,Scr,and UAE in the model group were higher than those in the control group. The levels of BUN,Scr and UAE in the probucol group and combination group were lower than those in the model group, and the levels of BUN,Scr,and UAE in the combination group were lower than those of the anisodamine group (all P <0. 05). ②The renal index in the model group was higher than that of the control group,and the renal index in the probucol group and the combination group was lower than that in the model group (all P < 0. 05). ③Compared with the model group,the NOS level increased and MDA decreased in the probucol group and anisodamine group (both P < 0. 05). The levels of SOD and T-AOC in the combination group were higher than those in the probucol group and anisodamine group (both P < 0. 05). ④Compared with the model group,the Bax expression decreased,the levels of Bcl-2 and the ratio of Bcl-2 / Bax increased in the probucol group and combination group (all P < 0. 05),and the ratio of Bcl-2 / Bax in the aniso-damine group increased (P < 0. 05). The ratio of Bcl-2 / Bax in the combination group was higher than that in the aniso-damine group (P < 0. 05). Conclusion The probucol combined with anisodamine can alleviate the renal injury of diabetic CIN rats. The mechanism may be related to the inhibition of oxidative stress and up-regulation of Bcl-2 / Bax ratio,and the effect is superior to single drug application.关键词
普罗布考/山莨菪碱/对比剂肾病/糖尿病/氧化应激/B细胞淋巴瘤/白血病-2基因/Bcl-2相关X蛋白质Key words
probucol/anisodamine/contrast-induced nephropathy/diabetes mellitus/oxidative stress/B cell lym-phoma/ leukemia-2 gene/Bcl-2 related X protein分类
医药卫生引用本文复制引用
高巧营,刘晋津,吴腾,张一,李东华,赵凯..普罗布考联合山莨菪碱对糖尿病大鼠对比剂肾损伤的影响[J].山东医药,2017,57(46):7-11,5.基金项目
天津市卫生局科技基金项目(2014KZ050). （2014KZ050）
