大蒜为百合科葱属植物的地下鳞茎,具有药食两用的价值,其含有大蒜素、二烯丙基硫醚、二烯丙基二硫醚、二烯丙基三硫醚、 硫-烯丙基半胱氨酸等多种生物活性成分,具有抗氧化、抗感染、免疫调节、心血管保护、抗癌等作用。不仅如此,大蒜在糖脂代谢的调节中功效显著,且相关机制日益明晰,主要包括保护胰岛β细胞功能、改善胰岛素抵抗、阻止脂肪细胞生长、抑制脂合成代谢及调节肠道菌群分布等。不同的提取工艺可影响大蒜的功效,其提取手段及药效关系值得进一步研究。

Garlic has values of both medicine and food,with rich allicin,diallyl disulfide（DADS）,diallyl trisulfide（DATS）and other garlic sulfur contents,which have been found to have multiple effets such as antioxidant,anti-infection,immunomodulatory,cardiovascular protection,anti-cancer,etc．Moreover,numerous studies have demonstrated that garlic plays an important role in the regulation of glycose and lipid metabolism,and the relevant mechanisms are becoming better understood,including protecting pancreatic β cells,improving insulin resistance,preventing the growth of fat cells,inhibiting lipid anabolism and adjusting the distribution of intestinal microflora．Different extraction processes can affect the efficacy of garlic,and further investigations are needed to elucidate the relationship between effective extraction methods and pharmacodynamic properties．

目的 本研究从细胞生物学角度检测二甲双胍对小鼠胰岛瘤MIN6的影响,并探讨此过程中包含的分子生物学机制。方法 MTT法检测不同浓度二甲双胍(1、2、5、10、20 mmol/L)对MIN6细胞活力的影响,细胞划痕实验检测二甲双胍对MIN6细胞迁移的影响,免疫印记实验检测此过程中细胞凋亡相关蛋白Bcl-2、Bax、caspase3表达的变化,及AMPK和JNK信号通路蛋白磷酸化水平的变化。结果 二甲双胍浓度大于10 mmol/L时可以抑制MIN6细胞的活力(P<0.01),降低其迁移能力(P<0.01),高浓度二甲双胍可以上调细胞内凋亡蛋白Bax(P<0.05)和p-AMPK的表达(P<0.05),降低抗凋亡蛋白Bcl-2的表达,增加caspase3剪切体(P<0.05)。同时,二甲双胍可以降低MIN6细胞内JNK信号通路的磷酸化水平(P<0.05)。结论 高浓度二甲双胍可以抑制MIN6细胞的增殖和迁移,其作用可能与降低了JNK信号的通路活化有关。

Objective This study aims to investigate the effect of metformin on proliferation and migration of MIN6 cells, and to explore the underlying mechanism. Methods The viability of MIN6 cells that were treated with various metformin (1,2,5,10 and 20 mmol/L) was detected by MTT assay. The migration of MIN6 cells was determined by wound-healing assay. Meanwhile, the proteins expression of Bcl-2, Bax, caspase3 and the phosphorylation of AMPK, JNK was detected by western bolt assay. Results The cell viability and the migration of MIN6 cells were decreased when the concentration of metformin above 10 mmol/L(P<0.01). The expression of apoptosis-related protein Bax(P<0.05) and p-AMPK(P<0.05)was up-regulated, anti-apoptosis-related protein Bcl-2 was down-regulated and cleaved caspase3 (P<0.05)was increased after high metformin treatment. At the same time, the phosphorylation of JNK was down-regulated by metformin(P<0.05). Conclusion High concertration of metformin may inhibit the proliferation and migration of MIN6 cells through suppressing the activation of JNK signaling pathway.

环孢素A(cyclosporin A,环孢素A)是强效的免疫抑制剂,常用于抑制器官移植后的排斥反应,器官移植后新发糖尿病与免疫抑制剂的使用有关。除器官移植,环孢素A还被用于治疗其他自身免疫性疾病,例如1型糖尿病。但环孢素A对胰岛β细胞和其他多种器官有毒副作用,长期使用环孢素A会导致胰岛素抵抗和胰岛β细胞功能损伤,这也是器官移植后糖尿病(post-transplant dibetes mellitus,PTDM)的主要原因。因此在糖尿病领域环孢素A的使用需要对病情进行具体分析和仔细斟酌。

Cyclosporin A (CsA) is a powerful immunosuppressant that is widely used to prevent organ rejection and to treat several autoimmune diseases, such as type 1 diabetes mellitus. Post-transplant diabetes mellitus (PTDM) is related with immunosuppressant. Moreover, there are many toxicity and side effects of CsA on pancreatic β cell and other organs, Long-term treatment of CsA may cause insulin resistance and β cell dyfunction. That's the main reason for post-transplant dibetes mellitus (PTDM). In diabetes mellitus fields, CsA must be used carefully considered.