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Efonidipine Exerts Cerebroprotective Effect by Down-regulation of TGF-β/SMAD-2-Dependent Signaling Pathway in Diabetic Rats
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2021-05-30 , DOI: 10.1007/s12031-021-01857-z
Rashmi Rajput , Vishal Chavda , Snehal S. Patel , George E. Barreto , Ghulam Md Ashraf

Calcium overload and hyperglycemia are risks of stroke onset in diabetics. Our study was designed to elucidate the beneficial role of calcium channel blockers by targeting voltage-gated calcium channels in diabetes-associated cerebrovascular complications. Diabetes was induced using the neonatal streptozotocin rat model. After confirmation of diabetes, middle cerebral artery occlusion (MCAO) was carried out. The pre-treatment with 1 mg/kg/day efonidipine was administered for the period of 4 weeks. After 24 h of ischemic induction surgery, the neurological score was determined, and blood was collected for determination of biochemical parameters. Treatment with efonidipine showed a significant reduction in post-ischemic brain infract volume, brain hemisphere weight difference, neurological score, Na+-K+ ATPase activity, serum CK-MB, and LDH levels in normoglycemic and hyperglycemic MCAO-induced animals. While no significant changes in glucose and lipid levels were observed by treatment, efonidipine significantly decreased the levels of malondialdehyde, acetylcholine esterase, and nitrite levels and increased the levels of antioxidant markers in both normoglycemic and hyperglycemic MCAO animals. TGF-β and VEGF were found to be down-regulated after treatment with efonidipine in gene expression study. In conclusion, the study data supports the cerebroprotective role of efonidipine in diabetic animals possibly through TGF-β/SMAD-2 signaling pathway.



中文翻译:

Efonidipine 通过下调糖尿病大鼠的 TGF-β/SMAD-2 依赖性信号通路发挥脑保护作用

钙超负荷和高血糖是糖尿病患者中风发作的风险。我们的研究旨在通过靶向电压门控钙通道在糖尿病相关脑血管并发症中阐明钙通道阻滞剂的有益作用。使用新生儿链脲佐菌素大鼠模型诱导糖尿病。确诊糖尿病后行大脑中动脉闭塞术(MCAO)。给予 1mg/kg/天依福地平的预处理持续 4 周。缺血诱导手术24 h后测定神经系统评分,采血测定生化参数。依福地平治疗显示缺血后脑梗死体积、脑半球重量差异、神经系统评分、Na + -K显着减少+正常血糖和高血糖 MCAO 诱导的动物中的 ATP 酶活性、血清 CK-MB 和 LDH 水平。虽然治疗后没有观察到葡萄糖和脂质水平的显着变化,但依福地平显着降低了丙二醛、乙酰胆碱酯酶和亚硝酸盐的水平,并增加了正常血糖和高血糖 MCAO 动物的抗氧化标志物水平。在基因表达研究中发现用依福地平治疗后 TGF-β 和 VEGF 下调。总之,研究数据支持依福地平可能通过 TGF-β/SMAD-2 信号通路对糖尿病动物的脑保护作用。

更新日期:2021-05-30
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