CAJ | 학술논문

目的：考察阿托伐他汀对糖耐量异常KKAy小鼠胰岛功能的影响并探讨可能作用机制。方法选择糖耐量异常的KKAy雌性小鼠模型。随机分为模型组和阿托伐他汀组（30 mg· kg -1· d -1），连续灌胃给药46 d，考察其对糖脂代谢及胰岛功能相关指标的影响。结果阿托伐他汀可显著降低KKAy小鼠血清脂质水平、血清胰岛素及胰岛素抵抗指数（ P＜0.05）；阿托伐他汀亦可显著降低口服糖耐量实验中药时曲线下面积（ P＜0.001），增加胰腺重量指数（ P＜0.01）；阿托伐他汀组胰岛中的炎性细胞浸润及脂肪空泡有一定程度减少，且β细胞阳性颗粒增多；阿托伐他汀可显著上调胰腺Bcl-2与SREBP2基因的表达水平（ P＜0.01， P＜0.05），并显著降低了Chop蛋白的表达水平（ P＜0.01）。结论阿托伐他汀可改善糖耐量异常KKAy小鼠的胰岛素敏感性和胰岛功能，可能与其改善机体糖脂代谢紊乱、调控胰腺中抗凋亡和内质网应激相关因子有关。
목적：고찰아탁벌타정대당내량이상KKAy소서이도공능적영향병탐토가능작용궤제。방법선택당내량이상적KKAy자성소서모형。수궤분위모형조화아탁벌타정조（30 mg· kg -1· d -1），련속관위급약46 d，고찰기대당지대사급이도공능상관지표적영향。결과아탁벌타정가현저강저KKAy소서혈청지질수평、혈청이도소급이도소저항지수（ P＜0.05）；아탁벌타정역가현저강저구복당내량실험중약시곡선하면적（ P＜0.001），증가이선중량지수（ P＜0.01）；아탁벌타정조이도중적염성세포침윤급지방공포유일정정도감소，차β세포양성과립증다；아탁벌타정가현저상조이선Bcl-2여SREBP2기인적표체수평（ P＜0.01， P＜0.05），병현저강저료Chop단백적표체수평（ P＜0.01）。결론아탁벌타정가개선당내량이상KKAy소서적이도소민감성화이도공능，가능여기개선궤체당지대사문란、조공이선중항조망화내질망응격상관인자유관。
Objective To evaluate the effects of the atorvastatin ( Ator) on βcell function in KKAy mice with impaired glucose tolerance ( IGT-KKAy ).Methods Female KKAy mice selected by insulin tolerance test ( ITT) were divided into two groups.Model group was orally adminis-tered by gavage with water , Ator group at a dose of 30 mg · kg -1 · d -1 for about 46 days.Normal C57 mice were recruited as Nor group.ITT, glucose tolerance tests ( OGTT) and fasting plasma lipids and insulin lev-els were determined.Pancreas weight index was tested.Pancreas mor-phology changes and βcell mass were evaluated by hematoxylin -eosin and gomori-aldehyde fuchsin stainning.The changes of gene and pro-tein expression in the pancreas were also analyzed by Real -time-PCR and Western bolt.Results Ator significantly improved glucose intoler-ance and insulin resistance in IGT -KKAy mice.Lipid profiles such as triglyceride ( TG) , total cholesterol ( CHO) , free fatty acid ( FFA) and low density lipoprotein cholesterol ( LDL-C) were all significantly di-minished after Ator treatment.Fasting plasma insulin levels and homeo-static model assessment -insulin resistance ( HOMA-IR) index were al-so decreased after treatment.In addition, Ator markedly increased pan-creas weight index , improved islets periphery and recovered βcell mass. It was showed that Ator up-regulated the pancreatic gene expression of anti -apoptotic Bcl-2 and cholesterol metabolism related SREBP2 (P<0.01,P<0.05).Moreover, the protein expression of ER stress related Chop is decreased in Ator group (P<0.01).Conclusion These results indicated that chronic administration of Ator improved dyslipidemia and glucose ho-meostasis in IGT-KKAy mice , which is related to up-regulation of genes involved in lipid metabolism and anti -apoptosis.The findings of the present study indicate that Ator might have a potential role for protecting βcell function.