摘要
目的观察罗格列酮钠对链脉佐菌素(STZ)糖尿病大鼠残存胰岛β-细胞的作用,及其对JNK信号通路的影响。方法SD大鼠随机分为正常对照组(6只),糖尿病对照组(OM组,14只),罗格列酮钠组(RSG组,14只),后两组予STZ(50mg/kg)腹腔内注射诱导成模后,RSG组予罗格列酮钠干预治疗〔4mg/(kg.d)〕。治疗10周后,各组大鼠行灌胃葡萄糖耐量试验,评价胰岛功能,之后处死动物,取胰岛组织,光镜下观察胰岛组织病理学形态,以免疫组化法检测胰岛中INS、P-JNK、Caspase-3的表达,TUNEL法检测β-细胞凋亡率。结果①与DM组相比,RSG组血糖降低。两组0hINS(FINS)和2hINS分别为(17.49±4.59)μU/Lvs(23.59±4.59)μU/L和(20.24±3.32)μU/Lvs(30.98±9.15)μU/L,RSG组INS水平更高,但差异无统计学意义(P=0.056),其胰岛功能有好于DM组的趋势。②RSG组较DM组的胰岛边缘较清晰,细胞排列较整齐,染色质较丰富。③RSG组胰岛表达INS的水平高于DM组(P<0.05)。④TUNEL检测结果显示RSG组的胰岛β-细胞凋亡率(%)较DM组小,分别为6.52±0.77vs10.33±1.07(P<0.05);Caspase-3的表达亦减少(P<0.05)。⑤与DM组相比,RSG组JNK的活化受到抑制,P-JNK的表达减少(P<0.05)。结论RSG能够减少胰岛β-细胞的凋亡,改善STZ糖尿病大鼠的胰岛功能,降低血糖,其对胰岛β-细胞的抗凋亡作用可能是通过JNK信号通路起作用的。
Objective To observe the effect of rosiglitazone sodium on survival of pancreatic β-cell of STZ induced diabetic rats and explore its impact on JNK pathway. Methods Total 34 SD rats were randomly assigned into three groups： control group （6 rats）, diabetic group （14 rats） and rosiglitazone sodium-treated diabetic group （14 rats）. STZ was administered intraperitoneally at a dose of 50 mg/kg for the latter two groups, then rosiglitazone sodium （4 mg/kg. d） was force-fed to diabetic rats in rosiglitazone sodium-treated group. Ten（10） weeks later, all the animals were subjected to oral glucose tolerance test to evaluate the function of pancreatic islet, then the rats were sacrified to obtain pancreatic tissue for histopathological study. The expression levels of INS, Caspase-3 and P-JNK in pancreatic islet were measured by immunohistochemistry and the apoptosis rates of β-cells were measured by TUNEL. Results （1） Compared with non-treated diabetic group, the levels of blood glucose （BG） in rosiglitazone sodium-treated group were lower at 0 h, 0.5 h, 1 h, 2 h in OGTT, which were （22.8±5.79） mmol/L vs （9.9±6.99） mmol/L, （29.33±3.29） mmol/L vs （25.63±4.56） mmol/L, （31.90±2.56） mmol/L vs （26.07±4.75） mmol/L, （25.08±3.53） mmol/L vs （21.47±6.64） mmol/L respectively（P〈0.05）. The levels of INS at 0 h and 2 h were [（17.49±4.59） μU/L（non-treated）] vs [（23.59±4.59） μU/L（treated）] and [（20.24±3.32） tμU/L（non-treated）] vs [（30.98±9. 15） μU/L （treated）] respectively, which showed INS of rosiglitazone sodium-treated group were higher, but without statistical significance（P= 0. 056）. The function of pancreatic islet in roslglitazone sodium-treated group seemed better than that of non-treated group. （2） Compared with non-treated diabetic group, the margin of pancreatic islets in rosiglitazone sodium-treated group were clearer, β-cells were more regularly arranged, chromatin were more abundant. （3） The lev
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2009年第3期430-434,共5页
Journal of Sichuan University(Medical Sciences)
