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

发布时间：2018-03-26 01:41

本文选题：普罗布考　切入点：山莨菪碱　出处：《山东医药》2017年46期

【摘要】：目的探讨普罗布考联合山莨菪碱对糖尿病大鼠对比剂肾病(CIN)的影响。方法选取130只大鼠制备糖尿病大鼠模型,将造模成功大鼠随机分为模型组、普罗布考组、山莨菪碱组、联合组各21只。另选10只正常大鼠为正常对照组。糖尿病造模9周后,普罗布考组及联合组给予普罗布考500 mg/kg灌胃,连续6 d;第8天时,于制备CIN模型前,山莨菪碱组及联合组经腹腔注射山莨菪碱100μg/100 g,15 min后,模型组、普罗布考组、山莨菪碱组、联合组经尾静脉注射复方泛影葡胺注射液0.8 m L/100 g制备CIN模型;1 h后,山莨菪碱组、联合组经腹腔注射山莨菪碱100μg/100 g共7次。注射对比剂前及24 h后,采用CBB法测定尿蛋白。内眦静脉取血,测定血清BUN、Scr水平。称重,开腹后采集左右肾脏并称重,计算肾指数。HE染色法观察肾脏组织病理变化。取肾脏组织制成肾组织匀浆,测定氧化应激指标包括一氧化氮(NO)、一氧化氮合成酶(NOS)、超氧化物歧化酶(SOD)、丙二醛(MDA)及总抗氧化能力(T-AOC)。荧光定量PCR法检测肾组织Bcl-2相关X蛋白质(Bax)和B细胞淋巴瘤/白血病-2基因(Bcl-2)mRNA表达。结果 (1)模型组BUN、Scr、UAE均高于正常对照组(P均0.05)。普罗布考组及联合组BUN、Scr、UAE均低于模型组,联合组BUN、Scr、UAE均低于山莨菪碱组(P均0.05)。(2)模型组肾指数高于正常对照组,普罗布考组及联合组肾指数低于模型组(P均0.05)。(3)与模型组比较,普罗布考组、山莨菪碱组肾脏NOS水平升高,MDA水平降低(P均0.05)。联合组肾脏SOD、T-AOC均高于普罗布考组和山莨菪碱组(P均0.05)。(4)与模型组比较,普罗布考组、联合组肾脏Bax表达水平降低,Bcl-2及Bcl-2/Bax升高(P均0.05);山莨菪碱组肾脏Bcl-2/Bax升高(P0.05),联合组肾脏Bcl-2/Bax高于山莨菪碱组(P0.05)。结论普罗布考、山莨菪碱联用可减轻糖尿病CIN大鼠的肾脏损伤,其机制可能与抑制氧化应激反应、上调Bcl-2/Bax比值有关,且效果优于单药应用。
[Abstract]:Objective to investigate the effect of probucol combined with anisodamine on diabetic rat nephropathy. Methods 130 diabetic rats were selected and randomly divided into three groups: model group, Probucol group and anisodamine group. After 9 weeks of diabetic modeling, probucol group and combined group were given probucol 500 mg/kg intragastric perfusion for 6 days. On the 8th day, before the CIN model was made, the rats in the probucol group and the combined group were treated with probucol for 6 days, and 10 normal rats were selected as the normal control group. The model group, probucol group, anisodamine group and combined group were injected intraperitoneally with anisodamine 100 渭 g / 100g for 15 min. The model group, Probucol group, anisodamine group were injected with compound meglumine diatrizoate (0.8 mL / 100 g) through tail vein for 1 hour. In the combined group, Anisodamine 100 渭 g / 100g was injected intraperitoneally for 7 times. Before and 24 hours after injection of contrast agent, urine protein and blood were measured by CBB method, and serum BUNT SCR levels were measured. The left and right kidneys were collected and weighed after laparotomy. The pathological changes of kidney tissue were observed by HE staining. The kidney tissue was made into homogenate of kidney tissue. The indexes of oxidative stress include nitric oxide (no), nitric oxide synthase (NOS), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (T-AOC). Fluorescence quantitative PCR assay was used to detect Bcl-2 related X protein Baxand B cell lymphoma. Results the mRNA expression of BUNG Scr-UAE in the model group was significantly higher than that in the normal control group (P < 0.05), and that in the Probucol group and the combined group was lower than that in the model group. The renal index in the model group was higher than that in the normal control group, and the renal index in the Probucol group and the combined group was lower than that in the model group and the model group, and the renal index in the probucol group was lower than that in the model group, and the renal index in the probucol group was lower than that in the model group. Compared with the model group, the renal NOS level in the combined group was higher than that in the Probucol group and anisodamine group. The expression of Bax in kidney of combined group was lower than that of control group (P 0.05), and that of kidney Bcl-2/Bax in anisodamine group was higher than that in anisodamine group (P 0.05). Conclusion Probucol and anisodamine can reduce renal injury in diabetic CIN rats. The mechanism may be related to the inhibition of oxidative stress and the upregulation of Bcl-2/Bax ratio, and its effect is better than that of single drug application.
【作者单位】：天津市南开医院;
【基金】：天津市卫生局科技基金项目(2014KZ050)
【分类号】：R587.2;R692

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