| Objective:(1)To observe FBG,FNS,TG,TC,Alb,BUN and Cr of the diabetic and Pioglitazone group rats.(2)To investigat the effect of Pioglitazone on the expression of mTOR in renal tissue of type 2 diabetic rats.Methods:Eight weeks thirty-Three healthy,sanitary Sprague-Dawley maleness rats whose body weight was (200±20) g included in this experiment were randomly divided into two groups.①Control group (group A,n=11);②Diabetic model group (n=22); Rats in group B and C were made type 2 diabetic model by feeding with high glucose high fat diet for four weeks,judging the rats appear insulin resistance status by HOMA insulin resistance index[HOMA=(FPG×FNS)/22.5], The insulin resistance index was (16.3±2.74),and then STZ(30mg·kg-1) with intraperitoneally injection once, rats in group A recived common diet for four weeks and a same volume of vehicle citrate buffer by intraperitoneally injection. After one week of STZ injection(all the rats were fasted for 12 hours),the fasting blood glucose was carried out by getting blood from tail vein,the fasting blood glucose for successful standard of diabetic model is 13.9. The rats which were diabetic model successfully were randomly divided into two groups, Diabetic model group (group B,n=11);Pioglitazone group (group C,n=11).Rats in group A and B recived a volume of 0.9% saline (2ml·kg-1·d-1)by intragastric administration, rats in group C recived Pioglitazone (10mg·kg-1·d-1) by intragastric administration. After six weeks, we collected 24h urine before the day we accomplish the experiment to detect urine albumin, and gathered blood of rats when we killed the rats in the end to detect blood glucose,blood insulin,TG,TC,Cr and BuN; kidneys of rats were removed,one renal was put into 4% formalin to detect the expression of mTOR by immunohistochemical staining, histopathological changes were done by HE staining; another was put into freezer for subzero eighty centi-degree to detected the expression of mTORmRNA by PCR.Results:(1) Biochemistry:Compared with group A,FBG,FNS,HOMA-IR,TG and TC of group B and C were enhanced (P<0.05); compared with group B, FBG,HOMA -IR,TG and TC of group C were decreased(P<0.05).(2) Renal function:Compared with group A,BUNand UAlb of group B and C were enhanced (P<0.05); compared with group B, BUN,Cr and UAlb of group C were decreased(P<0.05). Cr was no significant difference between group A and C.(3) Histopathological characteristics(HE staining):In group A the form of kidney cytoplasm were normal, and in group B, the kidney tubules epithelium appeared hyalinization and structurelessness dye red substance,part of the kidney tubules appeared liquefative necrosis and the structure of kidney tubules was indistinct,the bowman's capsule in kidney glomerulus exudated a little red blood cell, glomerular basement membrane was thicken, extracellular matrixc increased,the histopathological changes of group C were wosern than group B.(4) Immunohistochemical staining:The rats of every group express mTOR which appearansed brown granulation in kidney glomerulus and kidney glomerulus, compared with group A, the expression of mTOR in group B and C were enhanced (P<0.01), the expression of mTOR in group C was fewer than group B(P<0.05).(5) Related genes:Compared with the group A, the expression of mTORmRNA in group B and C were enhanced(P<0.05), The expression of mTORmRNA in group C was significantly fewer than group B(P<0.05).(6) The Correlation between UAlb and the expression of mTOR is positive Correlation,r=0.71(P<0.01).Conclusion:(1)The FBG,FNS,TG,TC and UAlb were significantly increased in diabetic rats, the drugs of Pioglitazone could reduce FBG,FNS,TG,TC and UAlb. (except Cr)(2) The expression of mTOR increased in diabetic rats, the drugs of Pioglitazone could inhibit the expression of mTOR. (3)It suggests that the drugs of Pioglitazone could improve glucolipid metabolism and insulin resistance in diabetic rats,thus they through regulating the expression of mTOR,which may put off diabetic nephropathy. |
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