Study On Endoplasmic Reticulum Strss Response Promoting Onset Of Rat Hippocampus Cell In Fluctuating Hyperglycemia

Objective1、To investigate experimental rat fluctuating hyperglycemia model and maintain highblood glucose fluctuation;2、To find out the influence of endoplasmic reticulum stressresponse in rats hippocampal neurons and the mechanism of increasing pathologicalchanges in fluctuating hyperglycemia, provide theoretical basis for clinical treatment andprevention of diabetes complicationsMethodsA single intra-peritoneal injection of streptozotocin(STZ) was adopted to induce diabeticrats models. The diabetic rats were randomly assigned into2groups,intermittent highglucose group(IHG),sustained high glucose group(SHG).Normal group which matchedthe former two groups on age,nest and body weight(C) was set up too. Each dayinjected insulin subcutaneous and(or) gavaged glucose twice at regular time.,and adjusteddosage according to the blood glucose levels.The two groups were given normal salineinstead.Tested5points of blood glucose once in a day each week, calculated MBG、SDBG、 LAGE to measure blood glucose stability. All rats were executed afterintervening for6weeks,then the expression levels of inositol requiring ER-to-nucloussignal kinase1(IRE1)、 Bcl-2、 CCAAT/enhancer-binding protein homologousprotein(CHOP)、78-kDa glucose-regulated protein （GRP78） were detected byimmunohistochemical method and Western blotting, while MDA content dection andSOD activation were tested under introduction. Structural changes in the hippocampal neurons are observed under electron microscopy,and TUNEL method was used to detectapoptosis of neurons.ResultComparied with C group,the IHG group and SHG group were presented as significantlyreduced activity,mixed colour,depression, increased eating,watering and urine, increasedmortality after moldle formed.The mortality of IHG group was higher than SHGgroup.The blood glucose fluctuation of SHG group and IHG group was more intensethan the C group, The expression of SDBG and LAGE were significant rised（p＜0.05）while MBG was reduced（p＜0.05）comparied to the C group,so as the IHG groupcomparied to the SHG group. By electron microscopy we found that,the organellesmorphology of IHG group has obviously changed, mitochondria,endoplasmic reticulumas long as other organelles were swelling of different level,some even had vacuolardegeneration which made them structural imperfected.Expression of IRE1、CHOP、GRP78and MDA content dection of IHG group were both higher than other groups（p＜0.05）when Bcl-2and SOD activation were totally droped relatived to the SHG group（p＜0.05）. TUNEL staining also promptted apoptosis increasing of hippocampal neuronsin IHG group.Conclusion1、Subcutaneous insulin injection and(or) gavage glucose twice in a day could establishthe intermittent glucose model on the basis of experimental diabetes model, and it workwell for the study of blood glucose fluctuation and its complications.2、The intermittent glucose promote an action on endoplasmic reticulum strss responsewhich lead to increased apoptosis of hippocampal neurons.