茶多酚治疗对糖尿病大鼠血浆中microRNA表达谱的影响

Effect of tea polyphenols treatment on microRNA expression profile in plasma of diabetes rats

目的了解茶多酚治疗后糖尿病大鼠血浆中微小RNA(microRNA)表达谱的变化,并分析其与糖尿病性骨质疏松的潜在关系。方法Sprague-Dawley大鼠随机分为:对照组(Con组)、糖尿病模型组(DOP组)以及治疗组[糖尿病模型+低剂量(4.8 g/kg)茶多酚组(DOP+L组)、糖尿病模型+中剂量(9.6 g/kg)茶多酚组(DOP+M组)、糖尿病模型+高剂量(14.4 g/kg)茶多酚组(DOP+H组)]。大鼠灌胃用药持续12周后,骨密度仪检测各组大鼠第5腰椎骨密度,Micro-CT扫描胫骨观察骨微结构。通过高通量测序方法获得各组大鼠血浆中microRNA的表达谱,并进行生物信息学分析。结果与DOP组比较,治疗组大鼠胫骨上段骨小梁数目有所增加,骨微结构明显改善,DOP+L、DOP+H组大鼠骨密度显著增高(P<0.05)。DOP与Con组差异表达显著的microRNA共252个(上调113个,下调139个),DOP与DOP+L组344个(上调213个,下调131个),DOP与DOP+M组350个(上调219个,下调131个),DOP与DOP+H组323个(上调209个,下调114个)。与Con组比较,DOP组的miR-382-3p表达显著降低,miR-96-5p和miR-21则明显升高;与DOP组比较,各治疗组的miR-382-3p表达明显升高,miR-96-5p和miR-21则明显降低(P<0.01或0.05)。结论茶多酚能有效改善糖尿病大鼠骨代谢异常;潜在的分子机制可能与改善microRNA的表达序列有关。

Objective To determine the changes of microRNA(miRNA)expression profile in plasma of diabetes rats after tea polyphenols treatment,and the potential relationship between microRNA(miRNA)expression profile and osteoporosis induced by diabetes.Method Sprague Dawley rats were randomly divided into:control group(Con),diabetes(DOP)model group,diabetes model low-dose(4.8 g/kg)tea polyphenols(DOP+L),middle dose(9.6 g/kg)of tea polyphenols(DOP+M)in diabetes model,high dose(14.4 g/kg)tea polyphenols(DOP+H)in diabetes model.After 12 weeks of oral administration,the bone density of the 5th lumbar vertebrae in each group of rats was measured by a bone density meter,and the microstructure of the tibia was observed by Micro CT scanning.the expression profile of microRNA in the plasma of rats in each group through high-throughput sequencing method and conduct bioinformatics analysis.Results Compared with the DOP group,the number of bone trabeculae in the upper tibial segment of rats in the treatment group was increased,the bone microstructure was significantly improved,and the bone mineral density of rats in the DOP+L and DOP+H groups was significantly increased(P<0.05).There were 252 differentially expressed microRNA in DOP and Con group(113 up-regulated and 139 downregulated),344 microRNAs in DOP and DOP+L group(213 up-regulated and 131 down-regulated),350 microRNAs in DOP and DOP+M group(219 up-regulated and 131 down-regulated),323 microRNAs in DOP and DOP+H groups(209 up-regulated and 114 down-regulated).Compared with the Con group,the expression of miR-382-3p was significantly decreased in the DOP group,while the expression of miR-96-5p and miR-21 was significantly increased.Compared with the DOP group,the expression of miR-382-3p was significantly increased in all treatment groups,while miR-96-5p and miR-21 were significantly decreased(P<0.01 or 0.05).Conclusion Tea polyphenols can effectively improve the abnormal bone metabolism in diabetic rats.The underlying molecular mechanism may be related to improving the expression sequence of microRNA.