摘要
目的观察雷公藤多甙(TWP)对非肥胖糖尿病(NOD)小鼠1型糖尿病的早期干预作用及探讨可能的机制。方法用环磷酰胺加速发病的NOD小鼠1型糖尿病动物模型,TWP组(30只)小鼠于实验第0~3天和第13~16天每日2次、第4~12天和第17~26天每日1次腹腔注射TWP,每次5mg/kg;对照组(33只)腹腔注射等量0.9%氯化钠溶液。监测血糖,记录糖尿病发病率,采用末端脱氧核苷酸转移酶标记法检测胰岛细胞凋亡,免疫组织化学法检测B细胞胰岛素含量,半定量逆转录聚合酶链反应检测胰腺和脾脏Fas及其配体(FasL)mRNA的表达。结果TWP组实验结束时的糖尿病发病率为43.3%,显著低于对照组的69.7%(P<0.05)。TWP组的凋亡指数为(5.06±0.85)%,显著低于对照组的(9.04±1.02)%(P<0.01)。TWP组胰岛素表达阳性细胞所占百分比为(57.25±11.69)%,略高于对照组的(46.50±11.25)%(P>0.05)。TWP组的胰腺组织FasmRNA半定量值为0.30±0.11,略低于对照组的0.35±0.05(P>0.05);TWP组的胰腺组织FasLmRNA半定量值为0.80±0.11,显著低于对照组的1.33±0.17(P<0.05)。TWP组的脾脏组织Fas和FasLmRNA半定量值分别为0.40±0.09和1.29±0.17,均显著高于对照组的0.27±0.06和1.06±0.10(P值均<0.05)。结论TWP可预防NOD鼠糖尿病的发生,其机制可能与增加脾脏T淋巴细胞Fas和FasL表达及凋亡,降低胰腺Fas和FasL表达,减少胰岛B细胞凋亡有关。
Objective To investigate the interventional effect of Tripterygium wilfordii ployglycosidium (TWP) on type 1 diabetes mellitus in non-obese diabetic (NOD) mice and explore its possible mechanism. Methods All NOD mice were administered with cyclophosphamide to accelerate the onset of diabetes. Mice in TWP group (thirty NOD mice) were treated intraperitoneally with TWP at a dose of 5mg/kg twice daily from day 0 to 3 and from day 13 to 16, or once daily from day 4 to 12 and from day 17 to 26. Mice in control group (thirty-three NOD mice) were administered with normal saline solution at the same volume and same time as in Group TWP. The glucose of NOD mice was monitored, apoptosis of beta-cell was detected by TUNEL, the level of insulin in the islet cells of the NOD mice were detected by immunohistochemistry, and the expressions of Fas and FasL mRNA in both pancreas and spleen were detected by reverse transcription polymerase chain reac- tion (RT-PCR). Results The incidence of diabetes in TWP group was 43.33% ,which was significantly lower than that in the control group (69.70%, P〈0.05). The apoptosis rate of beta-cell was lower in TWP group was significantly lower than that in the control group ([5. 06±0. 85] % vs. [9.04±1.02] %)%, P〈0.01). The insulin level in islet cells in group TWP ([57.25±11.69]%) was higher than that in the control group ([46.50±11.25]%), but there was no statistical difference (P〉0.05). The expression of Fas mRNA in the pancreas in TWP group was 0. 30±0.11, lower than that in the control group (0. 35±0.05), but with no significant difference (P〉0.05). FasL mRNA expression in the pancreas in TWP group was 0.80±0.11, which was significantly lower than that in the control group (1.33±0.17, P〈0.05). The expression of Fas mRNA and FasL mRNA in the spleen in TWP group were 0. 40±0.09 and 1.29±0.17, both significantly higher than those in the control group (0.27±0.06 and 1.06±0.10, P〈0.05). Conclusion TWP can prevent NOD mice from developing type 1 diabetes, which may be related to the up-regulation of Fas and FasL expression in the spleen, down-regulation of Fas and FasL expression in pancreas, and decrease of beta-cell apoptosis.
出处
《上海医学》
CAS
CSCD
北大核心
2008年第11期781-784,F0002,共5页
Shanghai Medical Journal
关键词
雷公藤多甙
1型糖尿病
非肥胖糖尿病鼠
FAS
FASL
Tripterygium wilfordii ployglycosidium
Type 1 diabetes
Non-obese diabetic mice
Fas
FasL