非诺贝特通过抑制增强的转化生长因子-β1/ Smad3信号通路减轻实验性糖尿病大鼠模型中的糖尿病肾病。
Fenofibrate attenuates diabetic nephropathy in experimental diabetic rat's model via suppression of augmented TGF-β1/Smad3 signaling pathway.
作者信息
Al-Rasheed Nouf Mohamed, Al-Rasheed Nawal Mohamed, Al-Amin Maha Abdelrahman, Hasan Iman Huesein, Al-Ajmi Hanaa Najeeb, Mohammad Raeesa Ahmed, Attia Hala Aboulfotooh
机构信息
a Pharmacology and Toxicology Department , College of Pharmacy, King Saud University , Riyadh , KSA.
b Pharmacology Department , College of Pharmacy, Princess Nora Bint Abdul Rahman University , KSA.
出版信息
Arch Physiol Biochem. 2016 Oct;122(4):186-194. doi: 10.3109/13813455.2016.1164186. Epub 2016 Apr 5.
CONTEXT
Fibrates, the ligands of peroxisome profileferator-activated receptor-α have been shown to have a renal protective action in diabetic nephropathy (DN).
OBJECTIVE
This study aimed to elucidate the effect of fenofibrate on renal transforming growth factor-β1 (TGF-β1) and Smad3 in Streptozotocin (STZ)-induced DN.
METHODS
Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were given fenofibrate (100 mg/kg, p.o.). After 12 weeks, diabetic nephropathy biomarkers were assessed. The mRNA expression of collage I and III, TGF-β1 and Smad3 and were detected by RT-PCR.
RESULTS
Fenofibrate reduced significantly serum creatinine, kidney/body weight ratio, serum albumin excretion Collage I & III, TGF-β1 and Smad3 mRNA expression.
CONCLUSIONS
Our results give further insights into the mechanisms underlying the protective role of fenofibrate in DN, suggesting that interference with TGF-β1/Smad3 signaling pathway may be a useful therapeutic approach to prevent DN.
背景
贝特类药物作为过氧化物酶体增殖物激活受体-α的配体，已被证明在糖尿病肾病（DN）中具有肾脏保护作用。
目的
本研究旨在阐明非诺贝特对链脲佐菌素（STZ）诱导的糖尿病肾病中肾转化生长因子-β1（TGF-β1）和Smad3的影响。
方法
通过单次腹腔注射链脲佐菌素（55mg/kg）诱导大鼠患糖尿病。给糖尿病大鼠口服非诺贝特（100mg/kg）。12周后，评估糖尿病肾病生物标志物。通过RT-PCR检测I型和III型胶原、TGF-β1和Smad3的mRNA表达。
结果
非诺贝特显著降低了血清肌酐、肾/体重比、血清白蛋白排泄量、I型和III型胶原、TGF-β1和Smad3的mRNA表达。
结论
我们的结果进一步深入了解了非诺贝特在糖尿病肾病中保护作用的潜在机制，表明干扰TGF-β1/Smad3信号通路可能是预防糖尿病肾病的一种有效治疗方法。
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