Protective Effects Of Lycium Barbarum Polysaccharides On Oxidative Stress Induced Apoptosis Of Peripheral Nerve In Type 2 Diabetic Rats And Its Mechanism

Objective To explore the protective effects of Lycium Barbarum Polysaccharides on Oxidatives Stress activated P38MAPK to induce apoptosis of peripheral nerve in type 2 Diabetic Rats and its mechanism, and to explore new ways on diabetic peripheral neuropathy in preventive effects.Method After 8 weeks,SD rats randomly were divided into two groups including normal control group and model group.The model group fed with high-sucrose-high-fat diet and injected with a low dose of STZ(35mg/kg) into abdominal cavity to induce hyperglycemia.The diabetic rats were randomly divided into four groups inculding model group and low,high doses of LBP groups andα-Lipoic acid group.To measure weight and nonfasting plasma glucose in 4th,8thand 10th after treatment.The rats were killed in 10th after tretment,and then the levels of blood fat in the blood scrum were detected.To take out the sciatic nerve which was observed by Morphometric evaluation under light microscope and transmission electron microscope.The content of SOD and MDA,GSH-Px in blood serum and sciatic nerve were detected. Bcl-2,Bax,P38MAPK and Caspase-3 expression of protein in dorsal root ganglion neuron by immunohistochemical method,and detecting the speed of conduction in sciatic nerve before being killed respectively.Result1,There was a raising up tendency in level of blood glucose and progressive decline in level of weight of model-control group(P<0.01).Compared with model group,LBP has significantly ameliorating to glucose and weight(P<0.05),but couldn't ameliorate to the normal level.α-Lipoic acid group has no significantly differences compared with model group. (P>0.05)2,Compared with the normal group, triglycerides,cholesterol and Low density lipoprotein of the model group is significantly rise . The level of cholesterol by reducing in high doses of LBP group was significantly differences compared with model group,(P<0.05)there's a tend the high doses of LBP group could reduce the level of triglycerides and Low density lipoprotein,and rise the level of High-density lipoprotein cholesterol.α-Lipoic acid group could not fall the action of hematic fat.3,Compared with the normal group,the sciatic nerve conduction velocity of the model group is significantly slow (P<0.01), the high doses of LBP group andα-Lipoic acid group both could accelerate the nerve conduction velocity and ameliorate to the normal level.And at the same time,these two groups were not significant difference in the therapeutic effect. (P>0.05)4,Compared with the normal group,the rats of model group have a significant increament in serum and sciatic nerve of MDA(P<0.01),but the content of SOD and GSH-PX in serum and sciatic nerve were obviously lower than that in the normal-control group in the corresponding time period. (P<0.01)When compared with the model group, the high doses of LBP group could elevate the content of SOD and GSH-PX in serum and sciatic nerve(P<0.05),although could not reach the normal level,but has no difference compared withα-Lipoic acid group in the therapeutic effect. (P>0.05)The high doses of LBP group andα-Lipoic acid group both could attenuate the content of MDA in serum and sciatic nerve to the normal level(P<0.05). 5,Compared with the normal group,there was obvious reactions to the damage in model group.However,the reactions in LBP group andα-Lipoic acid group were weaker than that in model group.6,By immunohistochemistric assays,we found that in model group,expression of Bcl-2 protein in dorsal root ganglion neuron significantly decreased compared with the normal group(P<0.01).but the expression level of Bcl-2 in DRG during the treatment process in LBP andα-Lipoic acid significantly increased,and the high doses of LBP group was superior ,it having significantly difference compared with model group(P<0.01). There's a tend the low doses of LBP group andα-Lipoic acid group could rise the expression level of Bcl-2,but there has no significantly difference compared with normal group(P>0.05).But in model group ,expression of Bax,P38MAPK and Caspase-3 protein in dorsal root ganglion neuron significantly increased compared with the normal group(P<0.01).but the expression level of Bax,P38MAPK and Caspase-3 in DRG during the treatment process in LBP andα-Lipoic acid significantly decreased,and the high doses of LBP group was superior ,it having significantly difference compared with model group(P<0.01). There's a tend the low doses of LBP group andα-Lipoic acid group could decrease the expression level of Bax,P38MAPK and Caspase-3,but there has no significantly difference compared with normal group. (P>0.05)Conclusion1,LBP can ameliorate the metabolisom of glucose and lipid ,also through this action on ameliorating weight in type 2 diabetic rats.2,The damages to structure and function of peripheral nerves in type 2 diabetic rats were found at advanced stages of DPN.It is the key link to cause occur and development of DPN that P38MAPK pathway was activated by Oxidative Stress to induce the apoptosis of dorsal root ganglion. 3,LBP may up-regulate the expression of Bcl-2,inhibiting expression of Bax,P38MAPK and Caspase-3 by control P38MAPK pathway ,and decreasing apoptosis may be through adjusting the oxidative stress state of organism.thus it can protect nerve cell from oxidative injury. LBP can lessen the damages to structure and function of peripheral nerves in diabetic rats.This may be one of the function mechanisms of protective effects of LBP on diabetic peripheral neuropathy.