Novel Thermosensitive Heparin-poloxamer Hydrogel Bridge NGF to Treat Peripheral Nerve Injury in Diabetics Rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of NGF-HP thermosensitive hydrogel on facilitating structural and functional regeneration in diabetic rats with sciatic nerve crush injury. METHODS: Eight-week-old male SD rats (200-220 g) were intraperitoneally injected wither steptozocin(STZ) to induce diabetes. After success of model establishment, the sciatic nerve of the diabetes rats were made crushed through two vascular clips force. Muscle and skin were then closed with 5-0 stitches. Following surgery, the rats were randomly divided into three groups PNI-diabetics group, free NGF group and NGF-HP hygrogel group. Each group received corresponding therapeutic drugs through a microsyringe. The motor recovery in all tested rats was assessed using Basso-Beattie-Bresnahan (BBB) locomotion scale and inclined plane test at indicated time points. After 30 d, rats were sacrificed, the crushed nerve and corresponding gastrocnemius muscle were harvested and the pathology index was assessed.The expressions of structural and functional proteins were detected through immunoblotting.The improvement of axon and myelination regeneration were evaluated via immunofluorescence, Masson′s trichrom stain and transmission electron microscope. RESULTS: NGF-HP not only had a good affinity for a certain amounts of nerve growth factor (NGF), but also controlled its release in a steady fashion in vitro. In vivo, compared with administration of direct free NGF, single injection of NGF-HP hydrogel was more effective at upregulating the expression of nerve associated structural and functional proteins, enhancing axonal regeneration and remyelination, as well as improving motor function recovery. CONCLUSION: This new type of hydrogel loaded with NGF shows striking effects on functional and morphometric recovery on peripheral nerve injury (PNI) following diabetes,which may provide a theoretical basis strategies for remedying PNI-diabetes in clinical populations.