| ObjectiveDomestic and foreign scholars generally believe that,the main reason of ischemia reperfusion injury is the effect of oxygen free radical.During reperfusion,oxygen free radicals are produced,over human's ability to withstand,tissue cells suffer irreversible damage.In clinical practice,Lipoic acid has been widely used in diabetic peripheral neuropathy,which due to its antioxidant and neuroprotective effects.Previous studies have confirmed that the peripheral nerve ischemia reperfusion injury can cause the apoptosis of spinal cord neurons.In order to study its possible neuroprotective effects in ischemia-reperfusion injury,we established a model of ischemia-reperfusion injury in the hindlimb of experimental rats,and to explore the effects and mechanism of Lipoic acid on peroneal nerve ischemia reperfusion injury in SD rats.MethodsThe 42 male SD rats were randomly divided into three groups.The control group has 6 rats(1)were not treated.We used the ischemia model in different time groups(2-7)by occluding the common iliac artery,internal iliac artery and external iliac artery of the left hind limb of the rats with arterial clamp for 1h,3h,6h.IR groups(2,4,6)and LA groups(3,5,7)have 18 rats respectively received normal saline or lipoic acid intraperitoneally before 6h reperfusion.the function of the hind limb was assessed using behavioral scores based on gait,racing reflex,toe spread,pinch sensitivity,paw position,and grasp.The common peroneal nerves and spinal cords were removed at the end of reperfusion times and sections were cut at 4um,then were stained for light microscopy studies and graded for edema and injury of common peroneal nerves,and the motor neuron apoptosis of the spinal cords.To investigate the effect of lipoic acid on the expression of Caspase-3 during ischemia-reperfusion injury in the hind limbs of rats.ResultsRats in the control group had normal hind limb function.In the IR group,the left hind limb function scores were significantly decreased(P<0.05);In LA group,the functional score of the left hind limb in ischemic 3h and ischemic 6h rats was higher than that of IR group(P<0.05).The peroneal nerve in the control group was normal.In IR group,the edema of the common peroneal nerve was more than 3,and more edema or atrophy in the axon,the nerve congest and swell,the nerve axon demyelination.After treatment with LA,the edema of nerve fibers was below 2,and the damage of axons and myelin were also improved.The difference has statistically significant(P<0.05).In control group,the neurons of the spinal cord were normal,and no obvious apoptosis,The Nissl bodies of neurons were uniformly stained,the nucleolus was obvious.In IR group,the neurons were scattered,the nuclei were condensed,the chromatin was marginal,and the nucleus was broken,and Nissl bodies were not clear.In LA group,the morphology of spinal neurons was normal,Nissl bodies in neurons was clear.In control group,no apoptotic neurons in spinal cord were found.In the IR group,there were obvious apoptotic neurons in the spinal cord of rats,the size of the nucleus was different,the chromatin was deep,and some cells were shrunken.In LA group,the apoptosis positive neurons were significantly decreased.In the ischemia 6h group,there was a significant difference between the LA group and the IR group(P<0.05).In control group,Caspase-3 no expression.In IR group,Caspase-3 expression was significant,but in LA group was significantly decreased(P<0.05).ConclusionsI/R of the lower limb artery can cause the injury of the common peroneal nerve and the apoptosis of spinal cord neurons.The longer the ischemia,the heavier the injury.Lipoic acid can relieve the nerve edema and neuronal apoptosis.Caspase-3 is involved in the formation of peripheral nerve IRI,LA can inhibit the expression of Caspase-3 protein.In conclusion,our findings suggest that post-ischemic administration of LA exhibits protective effect against common peroneal nerve I/R injury.LA can inhibit cell apoptosis,which enable it to be an important mechanism for the peripheral neuroprotection... |
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