The Protective Effect Of Baicalin And NGF Against Perepheral Nevrve Toxicity Caused By Colistin In Mice

In recent years, as the emergence of multi-resistant bacteria and the speed of development of new antibacterial drugs being limited, the colistin which was abandoned from clinical use due to its nephrotoxicity and neurotoxicity is taken seriously by people now. Colistin may be effective in the treatment of infection caused by Gram-negative bacteria, especially can be against infection caused by multi-resistant bacteria, but colistin-induced neurotoxicity seriously impacts on its therapeutic effect. The preliminary study established neurotoxicity model in mice by simulating clinical administration of intravenous colistin sulphate, the results showed:Colistin can injury the sensory and motor function in mice, the more sensitive indicators are the heat pain threshold and sensory nerve conduction velocity (SNCV), one of the important mechanisms colistin-induced neurotoxicity in mice is mitochondrial oxidative stress pathway.Baicalin is a kind of flavoniods compounds, which is extracted from the dried roots of Scutellaria baicalensis georgi. Baicalin has a lot of pharmacological effects, such as antioxidation, neuro-protection, anti-tumor, sedation, pathogenic microorganisms, immunomodulatory, anti-inflammatory. liver and gallbladder. anti-allergy et al. At present the reasrech of baicalin neuroprotection mainly focus on the brain nerve protection. but the protection of baicalin against colistin-induced peripheral nerves toxicity is unclear.NGF is one of the nerve growth factor family wich is the one studied most clear by people. NGF includes two receptors, receptor tyrosine kinases and non-receptor tyrosine-type P75. NGF exerts biological effectiveness after combining with its biological receptor. Nerve growth factor has a protective effect on central and peripheral nervous. However, there are few research on the protection of colistin-induced neurotoxicity.The experiment is divided into six dose groups:the normal group (saline), model group (intravenous colistin15mg/kg), baicalin high dose group (200mg/kg baicalin+15mg/kg colistin), baicalin media dose group (100mg/kg baicalin+15mg/kg colistin).baicalin low dose group (50mg/kg baicalin+15mg/kg colistin), NGF group (20μg/kg NGF+15mg/kg colistin)which the groups are continuous administration for7days and measured the General indicators(mental state observation and weight change), neurobehavioral parameters (gait analysis, grid test, thermal conductivity sleep test), oxidation-antioxidant parameters (MDA. SOD. CAT, GSH), sciatic nerve tissue expression of apoptosis-related factors (P53and BAX) detection and determination of MBP expression. The results showed that:By measureing general indicators, neurobehavioral indicators and sciatic nerve electrophysiology, it indicates that the baicalin and NGF can significantly improve the mental state of colistin in mice. the weight gain in mice, the sensory nerve dysfunction and improve sensory nerve conduction velocity in mice. NGF can significantly enhance nerve movement function in mice. but not in the baicalin intervention group, probably because the protective effect of baicalin is dose-dependent manner.By measuring the oxidative and antioxidantive indicators in sciatic nerve and serum in mice, It indicates that the baicalin and NGF could significantly reduce reactivity of oxygen indicators and improve the antioxidantive capacity in mice.By western Blot test for the detect of P53and BAX protein expression quantity in the sciatic nerve. baicalin and NGF can significantly reduce the expression of these two proteins.By western Blot for the detect of myelin basic protein (MBP) expression levels in sciatic nerve. baicalin and NGF can significantly reduce the expression levels of MBP.