黄连素改善妊娠期糖尿病大鼠胰岛素抵抗及其机制研究

目的 观察黄连素对高脂饲料喂养联合小剂量链脲佐菌素(STZ)诱导的妊娠期糖尿病(GDM)大鼠的作用及其可能机制。 方法 采用高脂饲料喂养雌性SD大鼠5周，交配受孕后第1天腹腔注射STZ(25 mg/kg)建立GDM大鼠模型，妊娠第1~19天黄连素溶液200 mg/(kg·d)]灌胃干预。监测各组大鼠孕期空腹血糖和胰岛素抵抗指数的变化。于妊娠第20天剖宫取胎，测量各组胎鼠和胎盘重量，通过实时荧光定量PCR法和ELISA法检测各组肝脏组织CRP、TNF-α基因和蛋白水平，通过Western blotting法检测肝脏细胞IKKβ和NF-κB蛋白的表达。 结果 与正常妊娠组相比，模型组孕鼠空腹血糖和胰岛素抵抗指数明显升高(均P＜0.05)，胎鼠和胎盘的重量明显增加(均P＜0.05)，肝脏组织CRP、TNF-α基因和蛋白表达增多(均P＜0.05)，肝细胞IKKβ蛋白和核NF-κB蛋白的表达增多(均P＜0.05)。经黄连素干预后GDM孕鼠肝脏细胞浆IKKβ蛋白和核NF-κB蛋白表达减少(均P＜0.05)，CRP、TNF-α基因和蛋白表达减少(均P＜0.05)，胰岛素抵抗指数和空腹血糖降低(均P＜0.05)。 结论 黄连素可以通过IKK/NF-κB信号通路，抑制NF-κB核转位，降低GDM模型大鼠肝脏组织中的炎症反应，从而改善胰岛素抵抗，降低血糖水平。 

Experimental study of berberine improving insulin resistance in gestational diabetes mellitus rat model and its possible mechanisms

Objective To explore the role of berberine in gestational diabetes mellitus (GDM) rat induced by high fat diet and low-dose STZ and its possible mechanisms. Methods After female SD rats were fed with high-fat diet for 5 weeks, STZ (25 mg/kg) was intraperitoneally injected on the first day after conception to establish the GDM rat model. The treatment of berberine by intragastric injection was from 1th to 19th day of pregnancy. The changes of fasting blood glucose and insulin resistance index in each group during pregnancy were detected. Pregnancy was terminated by caesarean on the 20th day of pregnancy, fetal and placental weights were measured and liver tissues were collected. The levels of TNF-α and CRP mRNA and protein were detected by real-time fluorescence quantitative PCR and ELISA; the expression of IKKβ and NF-κB protein was detected by Western blotting. Results Compared with normal pregnancy group, the fasting blood glucose and insulin resistance index of model group was significantly higher (all P<0.05), meanwhile fetal and placental weight increased (all P<0.05), the expression of CRP and TNF-α mRNA and protein in liver tissues was significantly increased, and the expression of IKKβ protein and nuclear protein NF-κB increased (all P<0.05). After treatment of Berberine, the expression of IKKβ, nuclear NF-κB, CRP and TNF-α in liver tissues of the model group was significantly decreased, the fasting blood glucose and insulin resistance index also decreased (all P<0.05). Conclusion Berberine can reduce inflammation in liver tissues, improve insulin resistance, and lower blood glucose levels in GDM rats through the inhibition of NF-κB nuclear transfer via IKK/NF-κB signaling pathway.