多球壳菌素对高糖诱导肾小球系膜细胞cyclinD1表达的影响

Effect of myriocin on the expression of cyclinD1 in high glucose-induced hypertrophy mesangial cells

摘要:

目的：多球壳菌素（ISP-1）是冬虫夏草中提取的一种新型免疫抑制剂，本研究旨在观察其对高浓度葡萄糖诱导的离体大鼠肥大肾小球系膜细胞（GMC）细胞周期蛋白D1(cyclinD1)表达的影响，并探讨其机制。方法利用体外培养大鼠GMC，予以高浓度葡萄糖（450 mg/dL D-glucose, HG）诱导GMC细胞肥大模型,同时以正常浓度糖 (100 mg/dL D-glucose, NG)培养作对照，并以加用ISP-1（450 mg/dL D-glucose+100 μg/mL ISP-1，ISP-1）干预作为干预组。采用流式细胞术检测GMC cyclinD1的表达。结果与NG组相比，HG组cyclinD1表达明显增高 (P<0.05)，且随时间的增加逐渐增强。ISP-1干预后可明显抑制高糖上调的cyclinD1表达，其在干预后48 h和72 h 的表达水平与NG组相比差异无统计学意义。结论高浓度葡萄糖可上调GMC cyclinD1的表达，而ISP-1可明显抑制高糖上调的cyclinD1表达的作用，这可能是ISP-1抑制高糖诱导GMC肥大的重要机制。

Abstract:

OBJECTIVE: Myriocin (ISP-1) is a new type of immune inhibitor extracted from cordyceps sinensis. This study was to observe the effects of ISP-1 on the expression of cell cycle regulatory protein D1 (cyclinD1) in high glucose-induced hypertrophy rat glomerular mesangial cells (GMCs). METHODS: Rat GMCs were cultured in vitro and divided into three groups: high glucose (450 mg/dL D-glucose), normal glucose (100 mg/dL D-glucose, control) and ISP-1 (450 mg/dL D-glucose plus 100 μg/mL ISP-1). The protein expression of cyclinD1 was detected by flow cytometry. RESULTS: The expression of cyclinD1 in GMCs in the high glucose group increased significantly in a time-dependent manner compared with that in the control group. ISP-1 treatment significantly inhibited the up-regulated expression of cyclinD1 induced by high concentration glucose, and the expression of cyclinD1 was restored to the level of the control group 48 and 72 hrs after ISP-1 treatment. CONCLUSIONS: High concentration of glucose can up-regulate the expression of cyclinD1 in GMCs. ISP-1 may inhibit the up-regulated expression of cyclinD1, which might contribute to the protective effect of ISP-1 against GMC hypertrophy induced by high glucose.