| Objective:This thesis focuses on establishment and evaluation of the best method for inducing rat model of type 2 diabetes mellitus, and investigation of the effect of Rehmannia glutinosa oligosaccharide (ROS) in type 2 diabetic rats and hyperglycaemia in normal rats and its mechanism.Methods:Experimental diabetic models were induced by ALX at the dose of 150 mg·kg-1 by intraperitoneal injection (i.p.), both high lipid food and low dose (30 mg·kg-1) of STZ by intravenous injection (i.v.), the single intraperitoneal injection of STZ (newly born rats, 90 mg·kg-1), or both high lipid food and low dose of STZ (30 mg·kg-1) by intraperitoneal injection, respectively. And plasma glucose, body weight and death rate were determined to select the best method for inducing type 2 diabetic rats model. Type 2 diabetic rats model was systematically evaluated in body weight, plasma glucose, hepatic glycogen, plasma lipids, weights of internal organs, as well as insulin and its counter-regulatory hormone levels (glucagons and corticosterone).According to the purpose of the experiment, type 2 diabetic model was induced by both high lipid food and low dose of STZ (30 mg·kg-1) in rats, hyperglycaemia in normal rats was induced by glucose (2.5 g·kg-1, i.p.) or adrenaline (300 μg·kg-1, i.p.). The animals were divided into control group, type 2 diabetic model group or hyperglycaemia model group, ROS (100, 200 mg·kg-1·d-1) treated group and metformin (200 mg·kg-1·d-1) treated group. All drugs were adiministered by intragastric administration (i.g.).Results:It was found that hyperglycaemia could be induced by ALX (i.p.) with a greatly decreased body weight. Hyperglycaemia could also be induced by both high lipid food and low dose of STZ (i.v.), but without good regularity. Hyperglycaemia induced in newly born rats by STZ (i.p.) was not feasible because of low achievement ratio, long period and high death rate. Only the hyperglycaemia induced by both high lipid food and low dose of STZ (i.p.) was stabile and with less influence on body weight and the death rate was not so high. The evaluations ofthis method were as follows: body weight decreased at first time, but increased later;plasma glucose was stabile and then increasing slowly;plasma lipids were observed with the changes of high TC level, high TG level and low HDL-C level;the weights of liver and kidney were increased and that of thymus decreased at first time, but increased later;insulin level and glucagons level decreased;corticosterone level decreased a little.As far as pharmacological effets of ROS was concerned, the plasma glucose levels in the ROS treated groups were decreased compared with type 2 diabetic model group, especially in high dose (200 mg-kg'^d'1, i.g.) treated group. ROS decreased the plasma TC level and TG level, increased plasma HDL-C level, improved body weight and increased spleen weight. In hyperglycaemia model induced by glucose (2.5 g-kg"1, i.p.) or adrenaline (300 jig-kg"1, i.p.), ROS decreased the peak of plasma glucose compared with model group.The activities of glucose-6-phosphatases and plasma corticosterone level in ROS treated groups were decreased compared with type 2 diabetic model group. On the other hand, the content of hepatic glycogen and plasma insulin level were increased compared with that of diabetic model group. In addition, ROS increased white blood cells and lymphocyte levels;improved platelet and mononuclear cell levels. The pathological examination proved that there were some damages in pancreas, which had been ameliorated by treatment of ROS in type 2 diabetic rats.Conclusion:Type 2 diabetic was induced successfully by both high lipid food and low dose of STZ in rats. The characteristic of this model was as follows: stabile plasma glucose and low release rate;the changes of plasma lipids were similar to that of type 2 diabetic in human being;easy to be maintained with slighter diabetic symptoms, compared with diabetic model induced by ALX.The plasma glucose level and plasma lipid level in ROS treated groups were decreased compared with type 2 diabetic model group. This effect may be related to the increase of hepatic glycogen level and insulin level, improvement of immunity and pancreas functions, and the decrease of activity of glucose-6-phosphatase and plasma corticosterone level. It was certified partly that the effect of ROS on type 2 diabetic rats was carried out by adjusting HPA axis function and had a close relationship with NIM network. In addition, ROS had hypoglycemic effect on glucose or adrenaline-induced hyperglycaemia rats.
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