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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。
Objective To investigate the effect of atorvastatin on islet function in KKAy mouse with impaired glucose tolerance and to explore the possible mechanism. Methods KKAy female mice with impaired glucose tolerance were selected. The rats were randomly divided into model group and atorvastatin group (30 mg · kg-1 · d-1). The rats were randomly divided into model group and atorvastatin group. The rats were orally gavaged for 46 days, and their effects on glycometabolism and islet function were investigated. Results Atorvastatin significantly decreased serum lipid level, serum insulin and insulin resistance index (P <0.05) in KKAy mice. Atorvastatin also significantly decreased the area under the curve of traditional Chinese medicine (P <0.001) in oral glucose tolerance test , And increase the weight index of pancreas (P <0.01). In atorvastatin group, the infiltration of inflammatory cells and adipocytes in the atorvastatin group decreased to some extent, and the number of positive β-cells increased. Atorvastatin significantly increased the expression of Bcl-2 And SREBP2 (P <0.01, P <0.05), and significantly decreased the expression of Chop protein (P <0.01). Conclusions Atorvastatin can improve insulin sensitivity and islet function in KKAy mice with impaired glucose tolerance, which may be related to the improvement of glucose and lipid metabolism and the regulation of anti-apoptosis and endoplasmic reticulum stress-related factors in the pancreas.