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孟鲁司特对链脲佐菌素诱导的大鼠糖尿病肾病模型的作用评估。

Evaluation of Effect of Montelukast in the Model of Streptozotocin Induced Diabetic Nephropathy in Rats.

作者信息

Kokate Dhananjay, Marathe Padmaja

机构信息

Department of Pharmacology and Therapeutics, Seth GSMC and KEM Hospital, Acharya Donde Marg, Parel, Mumbai, Maharashtra, India.

出版信息

Indian J Endocrinol Metab. 2024 Jan-Feb;28(1):47-54. doi: 10.4103/ijem.ijem_414_22. Epub 2024 Feb 26.

Abstract

BACKGROUND

Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy.

METHODS

40 Wistar rats of either sex were randomly divided into four groups . 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study.

RESULTS

Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group.

CONCLUSION

Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.

摘要

背景

糖尿病肾病是一种进行性疾病,是终末期肾病的主要原因。氧化应激和炎症在其发病机制中起重要作用。在临床前研究中,孟鲁司特已显示出肾脏保护和抗氧化特性,因此计划开展本研究以评估孟鲁司特在链脲佐菌素(STZ)诱导的糖尿病肾病模型中的作用。

方法

40只Wistar大鼠(雌雄不限)被随机分为四组。1. 赋形剂对照组;2. 依那普利(5毫克/千克)组;3. 孟鲁司特低剂量(10毫克/千克)组;4. 高剂量(20毫克/千克)组。第1天,通过腹腔注射单剂量STZ(60毫克/千克)诱导糖尿病。根据第7天的空腹血糖(FBG)水平验证糖尿病诱导情况,从第8天至第42天,给大鼠服用研究药物。在研究前和研究后评估FBG、血清肌酐、血尿素氮(BUN)和尿微量白蛋白水平。在研究结束时进行肾脏丙二醛(MDA)、还原型谷胱甘肽(GSH)评估和肾脏组织病理学检查。

结果

与赋形剂对照组相比,孟鲁司特10毫克/千克组的尿微量白蛋白水平显著降低(p < 0.05)。与赋形剂对照组相比,孟鲁司特20毫克/千克组的FBG、血清肌酐、BUN和尿微量白蛋白水平显著降低(p < 0.05)。此外,与赋形剂对照组相比,孟鲁司特20毫克/千克组对肾脏MDA和GSH水平(p < 0.05)以及组织病理学评分也显示出更好的效果。

结论

孟鲁司特因其抗氧化作用在糖尿病肾病模型中显示出保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c588/10962779/e4bc1bd9e693/IJEM-28-47-g001.jpg

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