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目的:观察番石榴叶总黄酮对链脲佐菌素(streptozocin,STZ)糖尿病模型小鼠胰腺组织中胰腺十二指肠同源盒因子-1(pancreas-duodenumhomeobox-1,PDX-1),神经元素3(neurogenin 3,Ngn3),NK6转录因子相关基因座1(NK6 transcription factor related locus 1,Nkx6.1)表达的影响,探讨其促进胰岛β细胞再生的机制。方法:将STZ糖尿病模型小鼠随机分为模型组和治疗组,治疗组包括番石榴叶总黄酮低、高剂量组及二甲双胍组,另设10只正常小鼠为正常组。番石榴叶总黄酮低、高剂量组按小鼠体重分别以番石榴叶总黄酮0.198,0.396 g·kg~(-1)·d~(-1)灌胃,二甲双胍组以二甲双胍0.087 5 g·kg~(-1)·d~(-1)灌胃,正常组和模型组以等体积蒸馏水灌胃,2周后检测其空腹血糖、体重,苏木素-伊红(HE)染色观察胰岛病理形态学改变,实时荧光定量聚合酶链反应(Real-time PCR)检测胰腺组织内胚胎期胰岛β细胞发育相关转录因子PDX-1,Ngn3,Nkx6.1 mRNA相对表达量。结果:与正常组比较,STZ糖尿病模型小鼠胰腺组织中PDX-1,Ngn3,Nkx6.1表达量明显下降(P<0.01);与模型组比较,番石榴叶总黄酮治疗组PDX-1,Ngn3,Nkx6.1 mRNA表达升高(P<0.05)。结论:番石榴叶总黄酮能上调糖尿病小鼠胰腺组织中PDX-1,Ngn3,Nkx6.1的表达;胰岛β细胞再生机制可能与PDX-1,Ngn3,Nkx6.1 mRNA表达的上调有关。
Objective: To observe the effects of total flavonoids from guava leaves on pancreatic duodenal homeobox-1 (PDX-1), pancreatic tissue in diabetic mice with streptozocin (STZ) (Neurogenin 3, Ngn3) and NK6 transcription factor related locus 1 (Nkx6.1), and to explore its mechanism of promoting islet β cell regeneration. Methods: The STZ diabetic mice were randomly divided into model group and treatment group. The treatment group consisted of low and high dosage of total flavonoids of guava leaves, metformin group and 10 normal mice as normal control group. The total flavonoids of guava leaves were low and the high dose groups were intragastrically administered with the total flavonoids of guava leaves 0.198,0.396 g · kg -1 · d -1 by weight respectively. The metformin group was treated with metformin 0.087 5 g · The rats in the normal group and model group were given gavage with equal volume of distilled water, and the fasting blood glucose and body weight were measured after 2 weeks. The pathological changes of the islets were observed with hematoxylin-eosin (HE) staining The expression of PDX-1, Ngn3 and Nkx6.1 mRNA in the pancreatic islet β-cell developmental embryos were detected by real-time PCR and real-time PCR. Results: Compared with the normal group, the expression of PDX-1, Ngn3 and Nkx6.1 in the pancreatic tissue of STZ diabetic mice decreased significantly (P <0.01). Compared with the model group, the PDX-1, Ngn3, Nkx6.1 mRNA expression increased (P <0.05). CONCLUSION: The total flavonoids in guava leaves can up-regulate the expression of PDX-1, Ngn3 and Nkx6.1 in pancreatic tissues of diabetic mice. The mechanism of islet β-cell regeneration may be related to the up-regulation of PDX-1, Ngn3 and Nkx6.1 mRNA expression.