The Management of Chronic Disease and Rehabilitation Department, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
Department of Chinese Traditional Medicine Research and Development Center, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6981-6991. doi: 10.3892/mmr.2017.7467. Epub 2017 Sep 12.
The aim of the present study was to compare the different effects of berberine (Ber) and Coptischinensis extract (CCE) on a rat model of type 2 diabetes mellitus (T2DM), and the islet Rin‑5f cell line was used to examine the differences between Ber and CCE and the underlying mechanisms. CCE was extracted and purified prior to analysis. Male Sprague‑Dawley rats were provided with a high‑fat diet to induce insulin resistance prior to injecting with streptozotocinto establish the T2DM model, the T2DM rats were treated with Ber and CCE, and blood samples and pancreatic tissues were obtained and compared to examine T2DM metabolic syndromes among the groups of rats, which included healthy rats, model rats, and model rats treated with Ber and CCE at different doses between 0 and 8 weeks. The protective effects of Ber and CCE on the Rin‑5f islet cell line were also evaluated. The effects on Rin‑5f cell proliferation and cell cycle, glucose‑stimulated insulin release test (GSIS), the anti‑apoptotic effects caused by fat induction, and protein expression levels of poly ADP‑ribose polymerase (PARP‑1) were evaluated. The results showed that the content of the prepared CCE was 96.07% for five alkaloids. When it was used for treatment of the T2DM rats, compared with Ber, metformin and rosiglitazone, the fasting blood glucose, glucosylated serum protein (GSP) and glucose infusion rate indicesin the fasting rats were ameliorated, compared with those in the T2MD rats, with no significant differences between treatment with Ber or CCE and metformin or rosiglitazone. The indices of mean optical density and fasting β‑cell function index (FBCI) were different following treatment with Ber and CCE, compared with those in the model rats, which may have stimulated the pancreatic secretion of insulin. When Ber and CCE were used to examine the protective effects on Rin‑5F cells, it was found that the Rin‑5f cell GSIS, cell cycle, lipotoxic islet cell proliferation and protein expression of PARP‑1 were altered and improved, which may have protected pancreatic islet β‑cells by improving islet β‑cell proliferation and the protein expression of PARP‑1. CCE and Ber exerted similar effects when used for the treatment of T2MD rats, and may have stimulated the pancreatic secretion of insulin through the protective effect on islet β‑cells via improving islet β‑cell proliferation and the protein expression of PARP‑1.
本研究旨在比较小檗碱（Ber）和黄连提取物（CCE）对 2 型糖尿病（T2DM）大鼠模型的不同作用，并使用 Rin-5f 胰岛细胞系研究 Ber 和 CCE 之间的差异及其潜在机制。在分析前提取并纯化了 CCE。先给雄性 Sprague-Dawley 大鼠高脂饮食诱导胰岛素抵抗，然后用链脲佐菌素注射建立 T2DM 模型，用 Ber 和 CCE 治疗 T2DM 大鼠，采集血样和胰腺组织，比较各组大鼠的 T2DM 代谢综合征，包括健康大鼠、模型大鼠和用不同剂量的 Ber 和 CCE（0 至 8 周）治疗的模型大鼠。还评估了 Ber 和 CCE 对 Rin-5f 胰岛细胞系的保护作用。评估了对 Rin-5f 细胞增殖和细胞周期、葡萄糖刺激的胰岛素释放试验（GSIS）、脂肪诱导的抗凋亡作用以及多聚 ADP-核糖聚合酶（PARP-1）的蛋白表达水平的影响。结果表明，制备的 CCE 中 5 种生物碱的含量为 96.07%。用于治疗 T2DM 大鼠时，与 Ber、二甲双胍和罗格列酮相比，空腹大鼠的空腹血糖、糖基化血清蛋白（GSP）和葡萄糖输注率指数均有所改善，与 T2DM 大鼠相比，Ber 或 CCE 与二甲双胍或罗格列酮的治疗效果无显著差异。与模型大鼠相比，Ber 和 CCE 治疗后平均光密度指数和空腹 β细胞功能指数（FBCI）不同，这可能刺激了胰岛胰岛素的分泌。当用 Ber 和 CCE 检查对 Rin-5F 细胞的保护作用时，发现 Rin-5f 细胞的 GSIS、细胞周期、脂毒性胰岛细胞增殖和 PARP-1 蛋白表达发生改变并得到改善，这可能通过改善胰岛 β 细胞增殖和 PARP-1 蛋白表达来保护胰岛 β 细胞。CCE 和 Ber 对 T2DM 大鼠的治疗作用相似，可能通过改善胰岛 β 细胞增殖和 PARP-1 蛋白表达来发挥对胰岛 β 细胞的保护作用，从而刺激胰岛胰岛素的分泌。
