Observation Of The Therapeutical Effect And The Mechanism Of Dioscorea Nipponica Makino On Diabetic Rat

Observation of the therapeutical effect and the mechanism of Dioscorea nipponica Makino on Diabetic RatObjective: To observe the therapeutical effect of Dioscorea nipponica Makino on diabetic rats with Insulin resistance and infer possible mechanism. Methods: Healthy male Wistar rats were fed of ordinary diet. Experimental groups were randomly divided into Dioscorea nipponica Makino group, rosiglitazone group and control group. The diabetic rat model was established by high fat diet one month and injection of streptozotocin. Successful model was difined as non-free plasma glucose ≥ 16.7mmol/L.Then modle rats were randomizedly redivided into Dioscorea nipponica Makino group, rosiglitazone group and control group. Normal group was given distilled water by intragastric administration. The three experimental groups were given Dioscorea nipponica Makino, rosiglitazone and distilled water by intragastric administration, respectively. When the rats' plasma glucose(GLU) were decreased to normal level or there was significant different comparing with the original was defined as effectiveness and put to death. After three months administration, all the rats would be put to death whether effective or not. We also measured weight, blood urea nitrogen(BUN), creatinine(CRE), total cholesterin(TC), triglyceride(TG), Insulin(INS) of different stage of the rats. Reserved the liver, renal, fat arroud the renal, muscle in liquid nitrogen. Reserved the liver, renal, pancreas and fixed them in 10% neutrality formalin. Detected the activity of NF-κ B in liver and renal by immunohistology , dyed liver, renal, pancreas with HE and observed their histology. Detected the expression of GLUT 4 mRNA in fat and muscle , PPAR- γ mRNA in fat, TNF- α mRNA in fat and TGF-β 1 mRNA in renal by RT-PCR. Results: ①After one month of high fat diet, the weight and Insulin were increased significantly. After injection of streptozotocin, blood glucose was increased significantly. ②After administration, the difference of GLU, BUN, CRE, TC, TG, INS and weight of the experimental groups of different stages were significant. GLU of Dioscorea nipponica Makino group and rosiglitazone group were decreased significantly. Dioscorea nipponica Makino group decreased 8.49mol/L (about 40% ) and rosiglitazone group decreased 7.03mmol/L (about 33%) .While INS of the two groups were significantly higher than control group, INS of rosiglitazone group was higher than that of Dioscorea nipponica Makino group, but they were all less than normal level. TC and TG of the experimental groups were all decreased significantly.③)The activity of NF- κB P65 in liver and renal: The activity of NF- κB P65 was significantly higher in contral group than in normal group, there was significant difference between the two groups (p<0.05) .In rosiglitazone group and Dioscorea nipponica Makino group the activity of NF- κB P65 in liver decreased 57.4% and 50.0% respectively and in renal it decreased 50.0% and 36.8% respectively. There was significant difference between these two groups and contral group (p<0.05), but there was no significant difference betweenthese two groups and normal group (p>0.05) .?The expression of GLUT 4 mRNA in muscle and fat: The expression of GLUT 4 mRNA was significantly lower in contral group than in normal group, there was significant difference between the two groups (p<0.05) . After therapy, the expression of GLUT 4 mRNA was significantly increased in rosiglitazone group and Dioscorea nipponica Makino group .The expression of GLUT 4 mRNA in Dioscorea nipponica Makino group in muscle and fat was increased 24.1% and 16.0% respectively and in rosiglitazone group it was increased 30.4% and 19.8% respectively.there was significant difference between these two groups and contral group(p<0.05), but there was no significant difference between these two groups and normal group (p>0.05) .?The expression of PPAR-y mRNA in fat: The expression of PPAR^y mRNA was significantly lower in contral group than in normal group, there was significant difference between the two groups (p<0.05). After therapy, in rosiglitazone group and Dioscorea nipponica Makino group the expression of GLUT 4 mRNA was increased 67.6% and 57.7% , respectively. There was significant difference between these two groups and contral group (p<0.05) , but there was no significant difference between these two groups and normal group (p>0.05 ) .?The expression of inflammation factors: The expression of TNF-a and TGF-B1 mRNA were significantly higher in contral group than in normal group, there was significant difference between the two groups (p<0.05) . After therapy, in rosiglitazone group the expression of TNF-a and TGF-B1 mRNA were decreased 16.3% and 24.8% .respectively. There was significant difference between rosiglitazone group and control group (p<0.05) , but there was no significant difference between rosiglitazone group and normal group (p>0.05 ). However, in Dioscorea nipponica Makino group, the expression of TNF-a and TGF-B1 mRNA were decreased either, but there was no statistic means. Conclusions: Dioscorea nipponica Makino has similar effect of reduce blood glucose with rosiglitazone and it's effect of increase the sensitivity of insulin may be prior to that of rosiglitazone. The mechanism of it's improving insulin resistance is may be it can excite the receptor of PPAR- Y, increase the expression of GLUT 4 mRNA, accelerate the arroud tissue such as muscle, fat to transport and utilize glucose and restrain the activity of NF- k B. The study pioneer a new way to cute type 2 diabetes with insulin resistance by Chinese medicine.We will study it's active components since then.Postgraduate: Chen Xinyan (Endocrinology) Directed by: Professor Zhao Shihua Professor Wang Yangang...