| Background:Alpha-lipoic acid(ALA)is a potent antioxidant and neuroprotective agent in the body.It can be produced endogenously on the mitochondrial membrane or exogenously.It has been widely used in clinical common neuropathy,such as diabetic neuropathy,central nervous system ischemia reperfusion injury and other diseases.Chronic compression injury to the sciatic nerve can cause changes in the structure and function of neurons in the Dorsal root ganglion(DRG),including ganglion neuronal apoptosis,fibrosis,reduced threshold of excitability,and hyperalgesia.Purpose:This experimental model simulates dorsal root ganglion injury caused by chronic compression of the sciatic nerve by ligating the rat's sciatic nerve.The purpose of this study was to investigate the effect of ALA on local oxidative stress in sciatic nerve injury and the effect on the expression of Bcl-2 in dorsal root ganglion neurons.Method:Fifty-four adult S-D rats which were randomly divided into ALA treatment group,NS control group and sham operation group.In the ALA treatment group,the skin was incised obliquely along the spine,the gluteal muscles were separated,the piriform muscles were retracted,the right sciatic nerve was exposed,and the right sciatic nerve was formed by a 4-0 non-absorbable line to ligate the animal model.Intraperitoneal injection of ALA 30mg/kg treatment daily.In the NS control group,the surgical operation was performed with the ALA treatment group,and an equal volume of NS was intraperitoneally injected daily.In the sham-operated group,only the right sciatic nerve was exposed and no ligation was performed.No drug intervention was performed after surgery.The three groups of rats were reared under the same conditions for 3 weeks for general observation.Preoperative 1d,postoperative 1d,7d,and 14 d,respectively,measured thermal latency latency.After 3 weeks,the sciatic nerves of three groups were taken for HE staining and determination of malondialdehyde content;L5 DRG was used for HE,Bcl-2 immunohistochemical staining to observe the morphological changes,degeneration,apoptosis and DR of neurons in DRG.-2 positive rate of expression.Result:General observation: After sciatic nerve ligation in rats,the lower extremities of the ALA treatment group and the NS control group immediately showed dyskinesia such as limping gait and toe weakness.As time progresses,toe atrophy,shedding of toenails,tarnishing of the skin and hair,and swelling of the feet are manifested.In the NS control group,1 case showed severe autophagy.There was no abnormal change in the rats in the sham group.HE staining results: HE staining showed that the number of DRG neurons in the NS control group was significantly reduced,and the cell body edema was severe and vacuolar degeneration occurred.Visible nuclear condensation is obvious and shows typical cell apoptosis.The degree of edema,degeneration,and apoptosis of neurons in the ALA treated group lighter than NS control group,and the neurons stained deeper.Thermal latency latency test results: There was no significant difference in PWL between the three groups of rats 1 day before surgery,P>0.05.The sham-operated group had PWL 1 day before surgery and postoperatively.Compared with 1 day before surgery,the PWL of the ALA treatment group and the NS control group was shortened on the 1st postoperative day,P<0.05;on the 1st postoperative day,the PWL of the ALA treatment group and the NS control group had no statistical significance.P>0.05.At 7d and 14 d after operation,the PWL time in the ALA treatment group was longer than that in the NS control group,P<0.05,they are significantly different.The sciatic nerve MDA test results: Compared with the sham operation group at 3w after surgery,the MDA level was increased in the ALA treatment group and the NS treatment group after surgery(P<0.05);the MDA level in the ALA treatment group was lower compared with the NS treatment group at 3w after the operation.(P<0.05).The results of Bcl-2 detection in dorsal root ganglion: At the 3rd week after operation,only a few positive cells were seen in the sham operation group;the ALA treatment group showed deeper staining and more positive cells;the NS control group also showed positive cells.Bcl-2 positive cell counts were compared between groups.The positive counts which in the NS control group were higher than the sham operation group,at 3 weeks postoperatively(P<0.05).There were more Bcl-2 positive cells in the ALA group than in the NS control group(P<0.05).Conclusion: 1.The local oxidative stress increased after sciatic nerve ligation in rats,and ALA can reduce the local oxidative stress.2.ALA can up-regulate the expression of Bcl-2 in DRG neurons. |
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