Effects Of Different Interventions On ACE、ACE2Expression And Ultrastructure Of The Pancreas In Type2Diabetic Rats

Objective:Through observation the effect of glycemic control of insulin glargine(INS) and(or) hedysari polysacchaide(HPS)、irbesartan(IRB)、hedysari polysacchaide and irbesartan(HA) on expression of ACE、ACE2, islet β cells’ultrastructure, islet function of the pancreas in the type2diabetes rats, to investigate possible protective mechanisms of different drugs and interventions to pancreatic affections at type2diabetes.Methods:NC group、DM group、HPS group、ARB group%HA group、INS group、IA group、1H group、IAH group,a total of nine groups,eight rats in each group for the study object,when the intervention end up,collect fasting venous blood and pancreas tissue of all rats,serum were collected after blood centrifugation to detect fasting insulin and C-peptide by radioimmunity,glycemic were measured by glucose oxidase method; expressions of ACE and ACE2mRNA in pancreas were tested by fluorescence quantitative RT-PCR; pancreatic ACE2proteinic expression were detected by immunohistochemistry SABC method; changes of pancreatic ultrastructure were observed by electronmicroscope; rate of islet P cells’apotosis were tested by tunel assay.Results:(1) Compare to NC group,body weight lost,ingestion volume、hydroposia volume%urine volume in24hours were higher(P<0.05),depressed、lazy、dull fur in T2DM rats, except body weight,general state which above mentioned were improved in all intervention groups in different degrees.Among which,the effect in groups of drugs application after glycemic control(IA、IH、IAH) were better than INS group and simple drugs groups (HPS、ARB、HA)(P<0.05).INS group was better than simple drugs groups (HPS、ARB、HA)(P<0.05),IAH group was the best (P<0.05),there is no obvious different between HPS、ARB and HA group,IA and IH group; body weight in all INS apply groups (INS、IA、IH、IAH) were higher than in DM group (P<0.05),but not to reach the level of NC group (P<0.05).There was on diffferent within INS apply groups (INS、IA、IH、IAH).Simple drugs apply (HPS、ARB、 HA) has no significant effect on body weight in type2diabetic rats. (2) Compare to NC group,expressions of ACE mRNA were higher,but the expressions of ACE2genic and proteinic were lower, early changes of apoptosis were appeared in the majority of islet β cell’ultrastructure,rate of islet β cells’apotosis were higher,the levels of fasting-insulin, fasting-C-peptide were less,but fasting glycemic were higher in T2DM rats (P<0.05).Though not reach the level in NC group(P<0.05),expressions of ACE mRNA were lower but expression of ACE2genic and proteinic were higher, islet β cells’ ultrastructure were improved, rate of islet β cells’apotosis were less,the levels of fasting-insulin and fasting-C-peptide were higher but fasting glycemic were less in all intervention groups.Among the indexes which mentioned above,the effect in groups of drugs application after glycemic control(IA、IH、IAH) were better than INS group and simple drugs groups (HPS、ARB、HA)(P<0.05).INS group was better than simple drugs groups (HPS、ARB、HA)(P<0.05).No matter whether combine glycemic control,effect of combination of chinese traditional drugs and western drugs were better than single drug application (P<0.05), there is no obvious different between HPS and ARB group、 IA and IH group.Conclusions:(1) Expression of ACE mRNA increase,ACE2mRNA and protein decrease in type2diabetes pancreas, islet β cells ultrastructure disorder and apoptosis increase,pancreatic islet function reduce,release of insulin and C-peptide diminish,glycemic step up,suggesting imbalance of ACE-Ang II-AT1axis and ACE2-Angl-7-Mas axis in pancreatic local RAAS was assiociated with pancreatic islet β cells’ dysfunction and structural damage.(2) HPS,IRB,INS were effective in treating type2diabetic rats pancreatic affections due to inhibition of ACE but promotion of ACE2in pancreas,improve islet β cells’ ultrastructure,decrease the rate of islet β cells’apoptosis,and then improve islet function,increase release of insulin and C-peptide,descend glycemic.Combination of chinese traditional drugs and western drugs after glycemic control is better than other methods,may be due to effect of this method to expression of ACE、IACE2in pancreatic local RAAS is more obvious.But the detail mechanisms need further experiments to confirm.