Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, India.
Neurol Sci. 2010 Dec;31(6):705-16. doi: 10.1007/s10072-010-0243-3. Epub 2010 Mar 6.
Enhanced production of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in diabetes leads to degradation of extracellular matrix in blood vessels and leads to complications of diabetes. In the present study, we have targeted MMP-2 and MMP-9 overactivation in diabetic neuropathy using a known MMP-2 and MMP-9 inhibitor, minocycline, with a non-selective COX inhibitor, aspirin. Streptozotocin-induced diabetic neuropathy was carried out in male Wistar rats and monitored by measuring the sensory nerve conduction velocity (SNCV), motor nerve conduction velocity (MNCV), tail flick latency and hot plate latency. Three weeks of treatment with a combination of minocycline and aspirin showed significant improvement in SNCV, MNCV, hot plate latency and tail flick latency when compared with diabetic control. The results of the present study suggest that MMP-2 and MMP-9 inhibition in the presence of COX inhibitor prevents the development of experimental diabetic neuropathy in rats and can be a potential approach for the treatment.
糖尿病导致基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的过度产生,导致血管细胞外基质的降解,进而引发糖尿病并发症。在本研究中,我们使用一种已知的 MMP-2 和 MMP-9 抑制剂——米诺环素,以及一种非选择性 COX 抑制剂——阿司匹林,靶向治疗糖尿病性神经病中的 MMP-2 和 MMP-9 过度激活。通过测量感觉神经传导速度(SNCV)、运动神经传导速度(MNCV)、尾巴拍打潜伏期和热板潜伏期,在雄性 Wistar 大鼠中进行链脲佐菌素诱导的糖尿病性神经病,并进行监测。与糖尿病对照组相比,米诺环素和阿司匹林联合治疗 3 周后,SNCV、MNCV、热板潜伏期和尾巴拍打潜伏期均显著改善。本研究结果表明,在 COX 抑制剂存在的情况下抑制 MMP-2 和 MMP-9,可预防大鼠实验性糖尿病性神经病的发生,这可能是一种有潜力的治疗方法。