2型糖尿病中国地鼠模型构建与小檗碱对肝脏过氧化物酶体增殖体激活受体及其靶基因表达的影响

背景：研究表明小檗碱可用于治疗2型糖尿病,但小檗碱治疗糖尿病胰岛素抵抗尤其是肝脏脂诱性胰岛素抵抗的分子机制仍不明确。目的：观察小檗碱对2型糖尿病中国地鼠模型肝脏过氧化物酶体增殖体激活受体及其靶基因表达的影响。方法：以高脂饮食及结合小剂量链脲菌素的方法建立胰岛素抵抗和2型糖尿病中国地鼠模型。建模后随机分成4组：对照组给予普通饮食,胰岛素抵抗组给予高脂饮食,2型糖尿病组给予高脂饮食＋小剂量链脲菌素,2型糖尿病小檗碱治疗组给予高脂饮食＋小剂量链脲菌素＋小檗碱,治疗9周。结果与结论：实时定量PCR结果显示与对照组相比,胰岛素抵抗及2型糖尿病组地鼠肝脏过氧化物酶体增殖体激活受体α,β/d,酰基辅酶A氧化酶,肉碱棕榈酰转移酶1和中链酰基辅酶A脱氢酶的表达降低（P〈0.05）,而固醇调节元件结合蛋白1c,2,过氧化物酶体增殖体激活受体γ,脂蛋白脂酶,脂肪酸转运者（FAT/CD36）和脂肪酸结合蛋白（ap2）的表达增加（P〈0.05）。结果证实,小檗碱可改善胰岛素抵抗,并逆转了氧化物酶体增殖体激活的受体及其靶基因表达的改变,小檗碱治疗2型糖尿病地鼠脂诱性胰岛素抵抗的分子机制与氧化物酶体增殖体激活的受体及其靶基因表达的改变相关。

Effects of berberine on expression of hepatic peroxisome proliferator-activated receptors and its target genes in type 2 diabetic Chinese hamsters

BACKGROUND：Although Berberine has been reported to treat type 2 diabetes,the underlying mechanisms of berberine on insulin resistance of type 2 diabetes,especially hepatic insulin resistance,remains not fully understood.OBJECTIVE：To study the effects of berberine on the expression of hepatic peroxisome proliferator-activated receptors（PPARs） and their target genes in type 2 diabetic Chinese hamsters.METHODS：The insulin-resistant and type 2 diabetic Chinese hamster models were induced by high-fat diet without or with low-dose streptozotocin.After the induction of models,the hamsters were randomly divided into normal control（standard food）,insulin-resistant（high-fat diet）,diabetic（high-fat diet and streptozotocin） and berberine-treated diabetic（high-fat diet and streptozotocin and berberine） groups.All groups were treated for 9 weeks.RESULTS AND CONCLUSION：Results of real-time quantitative PCR indicated that compared with normal control group,the expression of PPARα,PPARβ/δ,acyl-Coenzyme A oxidase（Acox）,carnitine palmitoyltransferase 1（Cpt1） and acetyl-Coenzyme A dehydrogenase,medium chain（Acadm） was decreased（P 0.05） and the expression of sterol regulatory element binding factor 1（SREBP1c）,sterol regulatory element binding factor 2（SREBP2）,PPARγ,lipoprotein lipase（LPL）,CD36/FA transporter（FAT/CD36） and adipocyte fatty acid-binding protein（ap2） was increased（P 0.05） in the fatty liver of insulin-resistant and diabetic hamster groups.Berberine effectively improved insulin resistance,reversed the altered expression of PPARs and its target genes in diabetic hamsters.PPARs and its target genes involved in the therapeutic molecular mechanisms of berberine on fat-induced hepatic insulin resistance in type 2 diabetic hamsters.