| The thesis consists of two parts. Part 1 is about insulin-resistance tree shrew model induced by high-glucose-fat-diet add dexamethasone. Part 2 tells about a new animal model to study type 2 diabetes mellitus by low-does streptozotocin intraperitoneally (i.p.) given to tree shrew.Part 1 Objective To induce an impaired glucose and lipid metabolism with high-glucose-fat feeding(HGF) plus DEX, laying the studying foundation for type 2 diabetes. Methods 14 normal male tree shrews were randomly divided into HGF group hypodermically injected (h.i.) with normal saline and HGF plus DEX group h.i. with dexamethasone at a does of 3mg/kg body weight, respectively. Their FBG, body weight, triglyceride, total cholesterol and glycosylated hemoglobin (HbAlc) were observed systematically before and after they were h.i. injected with DEX. Tree shrews weren't killed until the experiment finished, and the pathological changes of their pancreas, kidneys and livers were observed with light microscope. Results The FBG, lipid level and OGTT were significantly increased in HGF+DEX treated group compared with the HGF group while the fasting body weight reduced in both group. The pathological studies of HGF+DEX treated tree shrews'pancreas, livers and kidneys showed obvious classical pathological features of T2DM respectively. The pathological of pancreas are reduction of islets, degeneration of islet cells. The kidneys showed renal tubular epithelial cells atrophy, loss, fatty degeneration, fibrosis, and the tubular revealed dilatation, hyperemia calcification and protein cast. We also found a moderate liver steatosis. Conclusions High-glucose-fat feeding and DEX together can be used to induce glycometabolism and lipid metabolism abnormality.Part 2 Objective To grope for a method of inducing tree shrew model of type 2 diabetes mellitus(T2DM) with streptozotocin by intraperitoneal (i.p.) injection. Methods 22 nomal male tree shrews were divided at random into normal control group with 6 tree shrews and diabetes groups:STZ group with 8 tree shrews i.p. injected with STZ at the does of 120mg/kg body weight for three times (the 0 day, the 7th day and the 28th day) and DEX+STZ group with 8 animals, which h.i. injected with DEX at the does of 3mg/kg/d for 7 days firstly and then i.p. injected with STZ at the does of 120mg/kg at the 14th day and the 28th day respectively. The observed time was 15 weeks. Their FBG,body weight,TG and TC were observed systematically after they were injected with STZ or DEX. After FBG≥10.0mmol/L and kept this state more than 2 weeks the OGTT should be determined. We regard these tree shrews whose TG/TC have an evident increase compared to NC group as successful T2DM model. Tree shrews weren't killed until the experiment finished, and the pathological changes of their pancreas, kidneys and livers were observed with light microscope. Results The STZ group has the highest maki ng model success rate of 100%, the DEX+STZ group has only one out of 8 while the NC group is 0. All the succeed model tree shrew has insulin resistance, hyperglucemia, blood lipid disorder which are the typical characteristic of T2DM, and duration of high blood glucose was the longest(at least 80 days) and the most stabile too. The Pathological studies of the pancreas of those tree shrews whose FBG≥10.0mmol/L showed reduction of islets, degeneration of islat cells. The kidneys showed renal tubular epithelial cells atrophy, fatty degeneration and tubulointerstitial hyperaemia. Steatosis is the most pathology changes. Conclusions By i.p. injection STZ at the does of 120mg/kg for several times can induce a succeed tree shrew model of T2DM.
|
PDF Full Text Request