Effect Of Alpha-lipoic Acid On Oxidative Stress Caused Pancreatic Islet Beta Cell Apoptosis In Type2Diabetic Rats

To find out the possibility of making atifical type2diabetic ratmodel induced by high fat and high sugar diet and streptozotocin (STZ).To determine beneficial effect of alpha-lipoic acid on oxidative stressleading to apoptosis of pancreatic islet beta cell in type2diabeticrats.Type2diabetic rat model was induced by a single intraperitonealinjection of streptozotocin with the dose40mg/kg body weight,simultaneously, feeded with high fat and sugar diet.Experimental animalswere randomly divided into six groups：normal control,diabetes controland ALA(15mg/kg BW group,30mg/kg BW group,60mg/kg BW group and120mg/kgBW group).Rats in each group were scarified at three time points:4weeks,8weeks and12weeks from the onset of diabetes,with organscollected.The content of MDA,GSH-PX,ROS and the activities of T-SOD,CATwere assayed in each group at each time point,respectively.The changesof FBG,HbA1C, F-INS,TG,TC,HDL,LDL were tested at the sametime.Histopathological examination showed the changes of pancreasstructure in each group at each time point.The number of apoptoticpancreatic islet beta cell was detected by TUNEL assay.The proteinexpression of Bcl-2, Bax, Fas,Fas-L,Caspase-3and Caspase-9wasdetermined by western boltting assay.The incidence of type2diabetic rats induced by high fat and highsugar diet and STZ was87.91%. During the experiment period, type2diabetic rats almost all had stable diabetes signs.After antioxidativetreatment with ALA,compared to DM group, the content of FBE,HbA1C,TG andTC showed a descending trend in ALA groups.Simultaneously,the contentof F-INS has a tendency to increase in ALA groups.The effect of“60mg/kg BW”group was the most significant among all groups.Comparedwith control group,the content of MDA and ROS in serum and pancreatictissue of diabetic rats among ALA groups showed a significant increase.The activities of T-SOD and the content of CAT and GSH-PX in serum andpancreatic tissue of diabetic rats among ALA groups showed marklyreduction,compared as control group. After antioxidative treatment withALA, the content of MDA and ROS in serum and pancreatic tissue of diabeticrats among ALA groups showed a significant reduction,compared with DMgroup.The activities of T-SOD and the content of CAT and GSH-PX in serumand pancreatic tissue of diabetic rats among ALA groups showed marklyincrease,compared as DM group.There was a correlation between the changesof the indices and the duration of antioxidative treatment with ALA.Compared with control group, the number of apoptotic pancreatic islet betacells in DM group showed a markly increase. After antioxidativetreatment with ALA, compared to the DM group, the number of apoptoticpancreatic islet beta cells in ALA groups showed a significant reduction.There was a correlation between the changes of the indices and the durationof antioxidative treatment with ALA.Compared to control group,diabeticrats showed atrophy of pancreatic islets,decreased volume and decline ofislet cells.Compared to control group, the protein expression of Bax,Fas,Activated Cas-9was increased in pancreatic tissue of DM group,and theprotein expression of Bcl-2,Procaspase-9was decreased. Afterantioxidative treatment with ALA, at12weeks, compared to the DM group,the protein expression of Bax,Fas,Caspase-3,Activated Cas-9wasdecreased in pancreatic tissue of ALA groups,and the protein expressionof Bcl-2was increased.Making atifical type2diabetic rat model induced by high fat and highsugar diet and a single intraperitoneal injection of streptozotocin withthe dose40mg/kg body weight completed successfully. Antioxidant ALAcould increase the antioxidant ability of type2diabetic rats toattenuate oxidative damage pancreatic tissue caused by diabetes,andregulate of apoptosis related protein to result in a decline in oxidativestress leading apoptosis of pancreatic islet cells.So ALA maybe play arole in relieving the symptoms of diabetes.