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Study On Mechanism And Intervention Of ENOS On Diabetic Cerebral Microangiopathy

Posted on:2014-01-05Degree:MasterType:Thesis
Country:ChinaCandidate:X M LiFull Text:PDF
GTID:2234330398451681Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objective: To investigate the effect of eNOS signal pathway in type2diabetes cerebrovascular injury and intervention of gastric bypass surgery ontype2diabetic rats, rats model of type2diabetes mellitus were establish byhigh-fat food and Streptozotocin(STZ). Preoperative and postoperativeparameters,including the body weight, fasting blood glucose(FBG),serumlipid,fasting serum insulin(Fins),Homeostasis model assessment insulinresistance index (HOMA-IR) were dynamically observed.At the same time,the protein expression of FoxO1and eNOS in endothelial cells of cerebralmicrovascular was observed at eight weeks after the surgery.Methods:⑴Male SD rats with high fat diet for8weeks were injectedwith STZ(30mg/kg) in abdominal cavity to establish type2diabetes mellitusrats model.⑵24diabetic rats and24normal SD rats were randomized intotwo groups respectively:diabetes-operation group(DRO group),diabetes-shamoperation group (DSO group),normal-operation group(NRO group),normal-sham operation group(NSO group).Each group has12rats,and the ratswere operated with gastric bypass surgery or sham surgery.⑶Body weight,FBG,total cholesterol(TC),total glyceride(TG), Fins and HOMA-IR of eachgroup were detected before and after the operation.⑷8weeks after thesurgery, rat’s brain tissues of each group were taken out for the assessment ofprotein expression of phosphorylation FoxO1and eNOS in endothelial cellsof cerebral microvascular by immunohistochemistry.Results:1. Changes of rats’body weight in each group before and after surgery. Eight weeks after the surgery, body weight of the DRO rats decreasedfrom401.30±66.827g to337.80±71.731g(P>0.05),which was significantlylower than that of DSO group at the same time point(P<0.05).The rats’ bodyweight of the other three groups increased obviously (P<0.05).2. Changes of rats’FBG in each group before and after surgery.Eight weeks after the surgery, the FBG of the DRO rats decreased from23.580±4.2679mmol/L to9.500±1.3728mmol/L(P<0.05),which wassignificantly lower than that of DSO group at the same time point(P<0.05).There was no significant change in other three groups(P>0.05).3. Changes of rats’TC and TG in each group before and after surgery.Eight weeks after the surgery, the TC of the DRO rats decreased from2.032±0.3650mmol/L to1.444±0.3742mmol/L(P<0.05),and the TG of theDRO rats decreased from2.679±1.0876mmol/L to0.796±0.3889mmol/L(P<0.05),which was significantly lower than that of DSO group at the sametime(P<0.05). There was no significant change in other three groups(P>0.05).4. Changes of rats’Fins in each group before and after surgery.Eight weeks after the surgery, the Fins of the DRO rats decreased from21.730±1.191mIU/L to16.650±0.542mIU/L(P<0.05),which was significantlylower than that of DSO group at the same time point(P<0.05). There was nosignificant change in other three groups(P>0.05).5. Changes of rats’HOMA-IR in each group before and after surgery.Eight weeks after the surgery, the HOMA-IR of the DRO rats decreasedfrom22.811±4.695to7.034±1.100(P<0.05),which was significantly lowerthan that of DSO group at the same time point(P<0.05). There was nosignificant change in other three groups(P>0.05).6. The protein expression of phosphorylation FoxO1in rats’ cerebral microvasculaEight weeks after the surgery,the phosphorylation FoxO1proteinexpression of the DRO rats was obviously strenger than DSO group(P<0.05),but there was no obvious difference from the normal group(P>0.05).7. The protein expression of eNOS in rats’ cerebral microvasculaEight weeks after the surgery, the eNOS protein expression of the DROrats was obviously strenger than DSO group(P<0.05),but there was noobvious difference from the normal group(P>0.05)Conclusion:1. Eight weeks after the gastric bypass surgery, the body weight was notsignificantly increased, and the FBG, TC, TG, Fins and HOMA-IR of gastricbypass surgery group in type2diabetes rats were significantly lower than thatbefore surgery. The results showed that the operation may to a great extentrelieve type2diabetes.2. Eight weeks after the gastric bypass surgery, the phosphorylationFoxO1protein and eNOS protein expressed in endothelial cells of cerebralmicrovascular significantly increased in type2diabetes rats. The results couldprove that the operation can reduce the occurrence and improve the injury ofcerebrovascular by decrease the transcriptional activity of FoxO1and increasethe expression content of eNOS in diabetes.
Keywords/Search Tags:Gastric Bypass Sugery, Type2Diabetes Mellitus, CerebralMicrovascular, Foxo1, eNOS
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