Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Int Immunopharmacol. 2012 Apr;12(4):682-8. doi: 10.1016/j.intimp.2012.01.015. Epub 2012 Feb 11.
Metformin is a first-line antidiabetic drug in type 2 diabetes for its hypoglycemic activity, but recently researches also revealed the anti-inflammatory properties of metformin. In the present study, the pharmacological efficiency of metformin in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice was investigated. We found that pretreatment with metformin significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections, decreased myeloperoxidase (MPO) activity, reduced malondialdehyde (MDA) content in liver homogenates and increased survival rate of experimental animals. Metformin also markedly reduced hepatic TNF-α mRNA content and blood TNF-α level. Additional experiment showed that metformin significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by decreased caspase activities in liver tissues and reduced number of TUNEL-positive cells in liver sections. Furthermore, therapeutic administration of metformin after LPS/D-Gal challenge also improved the survival rate of experimental animal. These results indicated that the hypoglycemic reagent metformin could also provide therapeutic benefits in endotoxin-induced hepatic injury, suggesting its pharmacological potential in inflammation-base disorders.
二甲双胍是 2 型糖尿病的一线降糖药物，具有降糖作用，但最近的研究也揭示了二甲双胍的抗炎特性。在本研究中，研究了二甲双胍在半乳糖胺（D-Gal）敏化小鼠脂多糖（LPS）诱导的肝损伤中的药理作用。我们发现，二甲双胍预处理可显著降低 LPS/D-Gal 暴露小鼠的血清 ALT 和 AST 水平。这些都伴随着肝切片组织学改变的改善、髓过氧化物酶（MPO）活性降低、肝匀浆丙二醛（MDA）含量减少和实验动物存活率的提高。二甲双胍还显著降低了肝 TNF-α mRNA 含量和血液 TNF-α 水平。进一步的实验表明，二甲双胍可显著减轻 LPS/D-Gal 诱导的肝凋亡，这表现在肝组织中 caspase 活性降低和肝切片中 TUNEL 阳性细胞数量减少。此外，在 LPS/D-Gal 攻击后给予二甲双胍治疗也提高了实验动物的存活率。这些结果表明，降糖试剂二甲双胍还可以为内毒素诱导的肝损伤提供治疗益处，提示其在炎症相关疾病中的药理潜力。
