摘要
目的探讨4-苯基丁酸(4-PBA)对2型糖尿病(T2DM)大鼠胰岛β细胞内质网应激(ERS)诱导的细胞凋亡的保护作用。方法高脂饮食喂养加小剂量链脲佐菌素(STZ)腹腔注射建立SD大鼠T2DM模型,造模成功后取其中10只给予4-PBA灌胃20d。放射免疫法检测各组大鼠游离脂肪酸(FFA)、血糖及胰岛素的变化。醛品红染色观察胰岛形态改变,RT-PCR检测内质网相关蛋白(Caspase-3、GRP78、CHOP)的mRNA表达变化。结果高脂对照组(n=10)和T2DM组(n=8)大鼠血清FFA比正常对照组(n=10)显著增加,4-PBA治疗后显著下降(n=8)。4-PBA治疗升高了T2DM造成的血清胰岛素水平降低,并降低了T2DM引起的高血糖。醛品红染色显示,T2DM大鼠胰岛萎缩,数量显著下降,胰岛细胞胞质内出现空泡,4-PBA治疗后胰岛数量相比T2DM组有所增多。与对照组相比,T2DM组Caspase-3和CHOP的mRNA表达升高,4-PBA治疗后显著降低。结论 4-PBA通过CHOP途径减轻ERS对胰岛β细胞的损伤,抑制胰岛细胞的过度凋亡,保护胰岛β细胞功能,从而延缓2型糖尿病的发展。
Objective To evaluate the therapeutic effect of 4-phenylbutyric acid （4-PBA） on endoplasmic retieulum stress of type 2 diabetic （T2DM） rats. Methods To establish a T2DM model in SD rats with injection of low doses streptozotocin（STZ） after being fed with high-fat diets. Ten T2DM rats were treated with 4-PBA for 20 days. The free fatty acids （FFA）, insulin and blood glucose were observed by the radioimmunological method. The pathological changes of pancreatic islet were detected by aldehyde fuchsin staining. The level of mRNA of the endoplasmic reticulum stress associated molecules （ Caspase-3, GRP78, CHOP） was tested by RT-PCR. Results The concentration of FFA increased significantly in T2DM group （n = 8）and high-fat diets group（ n = 10） compared with control group（ n = 10 ）. 4- PBA significantly suppressed FFA caused by high-fat diets（ n = 8）. The use of the 4-PBA prevented the decrease of insulin in T2DM group and prevented the increase of blood glucose in T2DM group. Aldehyde fuchsin staining showed that, in the T2DM group, the number of pancreatic islet decreased, the shape of pancreatic islet became unreagular, and vacuoles appeared in cytoplasma. The number of pancreatic islet increased after treatment of 4-PBA. The expression of Caspase-3 and CHOP mRNA in T2DM group significantly increased with those in control group and high-fat diets group. Enhancedexpression of Caspase-3 and CHOP was decreased by 4-PBA. Conclusion Our data suggest that chemical chaperone 4- PBA may prevent the development of T2DM associated with the decreased expression of the CHOP.
出处
《解剖学报》
CAS
CSCD
北大核心
2012年第6期784-788,共5页
Acta Anatomica Sinica
