黄连素对2型糖尿病中国地鼠肝脏固醇调节元件结合蛋白转录调节系统表达的影响

Effects of berberine on expression of hepatic sterol regulatory element-binding protein,its control and target genes in type 2 diabetic Chinese hamsters

[目的]研究黄连素对2型糖尿病中国地鼠肝脏固醇调节元件结合蛋白(SREBPs)、其调控基因及靶基因表达的影响,探讨黄连素治疗脂诱性肝胰岛素抵抗的分子机制。[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。成模后随机分成正常对照组、胰岛素抵抗组、2型糖尿病组和2型糖尿病黄连素治疗组,治疗9周。应用实时定量PCR方法检测各组地鼠肝脏SREBPs、其调控基因及靶基因的表达。[结果]PCR结果显示模型地鼠脂肪变的肝脏中SREBPs基因、SREBPs切割激活蛋白(SCAP)基因、蛋白酶S1P和S2P基因和SREBPs靶基因的表达增加,胰岛素诱导基因(Insigs)的表达降低。黄连素有效地改善胰岛素抵抗,同时,逆转了SREBPs、其调控基因及靶基因表达的改变。[结论]SREBPs转录调控系统参与黄连素治疗2型糖尿病地鼠脂诱性肝胰岛素抵抗。

[Objective] To study the effects of berberine on the expression of hepatic sterol regulatory element-binding protein（SREBPs） and their control and target genes in type 2 diabetic Chinese hamsters and explore the therapeutic molecular mechanisms of berberine on fat-induced hepatic insulin resistance.[Methods] The insulin-resistant and type 2 diabetic Chinese hamster models were induced by high-fat diet without or with low-dose streptozotocin.Then,the hamsters were randomly divided into 4 groups：normal control,insulin-resistant,diabetic and berberine-treated diabetic groups.After nine-week treatment,the expression of hepatic SREBPs and their control and target genes from different groups were measured by RT-PCR.[Results] It was indicated that the expression of SREBPs,SCAP,S1P,S2P and SREBPs target genes was increased and the expression of Insigs was decreased in the fatty liver of hamster model.Berberine effectively improved insulin resistance and reversed the altered expression of hepatic SREBPs and its control and target genes in diabetic hamsters.[Conclusion] SREBPs gene transcriptional programs are involved in the therapeutic molecular mechanisms of berberine on fat-induced hepatic insulin resistance in type 2 diabetic hamsters.