| 1.THE STUDY OF PROBUCOL ON PROTECTION OF PANCREATIC Β-CELLS IN STZ-INDUCED DIABETES MICE AIMS: To study the effect of probucol on protection of pancreatic β-cells in STZ-induced diabetes mice . METHODS: The mice were divided into four groups with ten mice each randomly. First group was given standard food(C group), second group was given standard food and 1% probucol(C+T group), third group was given standard food and was treated with multiple low-dose STZ(D group);and forth group was given standard food, 1% probucol and was treated with multiple low-dose STZ(D+T group). The preventive intervention was undertaken with standard diet mixed with 1% probucol in Kunming mice .One week after benginning of each diet ,STZ was injected 50mg/Kg body weight intraperitoneally once daily for five days. At 0, 1, 2, 3 weeks after the last injection of STZ, fasting blood glucose was measured with tail blood of mice. At 3 week serum insulin and glucose tolerance test was done.Insulin in beta cells of islets was detected with immunohistochemical analyses and analysed with image analyzer.The mumber of beta cells and pathological changes were investigated under light microscope . RESULTS: The fasting blood glucose at 0,1,2,3 weeks in D+C group was lower than that in D group([9.32±0.57 VS 11.74±0.69 mmol/L,P<0.05)(,10.23± 0.61VS17.68 ±1.34 mmol/L,P<0.01),(11.45±0.621VS 18.94±1.55 mmol/L,P<0.01),(12.67±0.72VS19.79±1.61 mmol/L,P<0.01)];At 3 week in D+C group glucose tolerance was significantly improved (P<0.05 or 0.01)and compared with the D group, D+C group serum fasting insulin was increased (25.78±4.36 VS 13.32±3.02, P<0.01 ).The insulin proteins of mice pancreas tissue were detected by immunohistochemical method . Insulin content of beta cells in D+C group was markedly higher than that in D group [( insulin area density :45.84±7.92 VS6.98±1.32 % p<0.01 ),(gray scale:1.82±0.06 VS 1.48±0.07 p<0.05)];Beta cells were significantly increased in D+C group compared with the D group(41.75±19.67VS12.28±11.62 p<0.05)。CONCLUTION: Probucol could reduce fasting blood glucose and improve glucose tolerance by protection of pancreatic β-cells in STZ-induced diabetes mice. 2.EFFECTS OF PROBUCOL ON APOPTOSIS OF BETA CELLS AND NF-KB IN STZ-INDUCED DIABETES MICE AIMS: To explore effects of probucol on apoptosis of beta cells and NF-Kb in STZ-induced diabetes mice. METHODS: Grouping and diabetes animal model were same with part one. Within 24 h after the last injection of STZ, blood sample was collected for detecting insulin and after mice was sacrificed, pancreas was removed . The apoptosis index of beta cells was detected by TUNEL and the ultrastructure of islets was observed by electron microscope. The NF-KBp65 protein was detected with immunohistochemical method and the mRNA expression of NF-KBp65 was assessed by RT-PCR. RESULTS:Compared with the D group, serum fasting insulin of D+C group was increased markedly (24.57±4.13 VS 30.71±4.06, P<0.01 ). The apoptosis index of beta cells in D+C group was lower than that in D group(11.32±3.60 VS 25.79±6.82,P<0.05). NF-KBp65 protein and gene expression of NF-KBp65 of D+C group was markedly decreasedcompared with the D group[(15.84±1.76 VS32.47±1.01, P<0.05) and (0.845±0.013 VS 1.137±0.018,P<0.05)]. In D+C group apoptosis of beta cells was not investigated and in D group was investigated by electron microscope. CONCLUTION: Decreased apoptosis of beta cells may be an important mechanism of protecting beta cells of probucol in STZ-induced diabetes mice. STZ could activate NF-KB and probucol can suppress the activit of NF-KB and mRNA expression NF-KBp65. This suggested that the change of NF-KB was associated with apoptosis of beta cells in STZ-induced diabetes mice. 3. EFFECTS OF PROBUCOL ON OXIDASE , FREE RADICAL, GENE EXPRESSIONS OF PDX-1 AND INSULIN IN STZ-INDUCED DIABETES MICE AIMS: To study the effects of probucol on oxidase , free radical, gene expressions of PDX-1 and insulin in STZ-induced diabetes mice.METHODS: Grouping and diabetes animal model was the same wit... |
PDF Full Text Request