科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background and Objective: Mitochondrial improvement is the central player of neuroprotection following spinal cord injury (SCI). The present study evaluated the neuroprotective and anti-inflammatory effects of a new mitochondrial-acting drug, ginsenoside compound Mc1 (GCM), in rats with traumatic SCI, by focusing on the role of mitochondrial ATP-sensitive potassium (ATP-KCh) channels and mitochondrial biogenesis. Materials and Methods: The SCI was modelled in Sprague Dawley rats (n = 60) through laminectomy and placing an extradural aneurysm clip at the T10 vertebral level. The GCM at the concentrations of 20 and 40 mu M was intraperitoneally administered to rats at 1, 6 and 12 hrs after laminectomy. Locomotor activity, spinal cord histology, mitochondrial function and biogenesis and the levels of pro-inflammatory cytokines were quantified. Results: Administration of GCM significantly reduced SCI-induced neurological locomotor deficits and histopathological findings in a dose- dependent manner, as compared with the untreated control group (p<0.01). The GCM (40 mu M) significantly reversed the SCI-induced changes in mitochondrial membrane depolarization, mitochondrial reactive oxygen species (mitoROS), ATP levels, superoxide dismutase (mnSOD) and pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-8 (p<0.01). As well, the expression of mitochondrial biogenesis proteins PGC-1 alpha, NRF1 and TFAM was upregulated following GCM 40 mu M treatment. Importantly, the inhibition of mitochondrial ATP-KCh through hydroxydecanoate significantly eliminated the neuroprotective, anti-inflammatory and mitochondrial impacts of GCM. Conclusion: The GCM post-treatment had a significant neuroprotective effect on SCI which was mediated through increasing mitochondrial ATP-KCh activity and subsequent improvement of mitochondrial biogenesis and function and reduction of inflammatory responses.
-
单位南方医科大学; 1
