Ismail Hassan Fatima, Didari Tina, Baeeri Maryam, Gholami Mahdi, Haghi-Aminjan Hamed, Khalid Madiha, Navaei-Nigjeh Mona, Rahimifard Mahban, Solgi Sara, Abdollahi Mohammad, Mojtahedzadeh Mojtaba
Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.
School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Cell J. 2020 Jul;22(Suppl 1):29-37. doi: 10.22074/cellj.2020.7046. Epub 2020 Jul 18.
Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed.
In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out.
Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 () and claudin 5 () were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (), and glial fibrillary acidic protein ().
Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.
二甲双胍对炎症和氧化应激具有强大的抑制活性，而炎症和氧化应激在脓毒症相关性脑病（SAE）中不可避免地会发生。二甲双胍在SAE中发挥神经保护作用的确切机制仍不清楚。在本研究中，我们评估了二甲双胍对采用盲肠结扎穿孔（CLP）脓毒症模型的SAE的保护作用。
在本实验研究中，对Wistar大鼠进行CLP手术，并立即给予50mg/kg二甲双胍。研究了脓毒症严重程度、炎症、血脑屏障（BBB）功能障碍和脑损伤的特异性标志物。使用了特异性检测试剂盒和实时聚合酶链反应（RT-PCR）。还进行了组织病理学评估。
二甲双胍治疗降低了小鼠脓毒症评分（MSS）、乳酸水平、血小板淋巴细胞比率（PLR）和高迁移率族蛋白B1（HMGB1）水平。二甲双胍治疗后，紧密连接蛋白claudin 3（）和claudin 5（）的表达水平升高。二甲双胍降低了S100b、神经元特异性烯醇化酶（）和胶质纤维酸性蛋白的表达。
我们的研究表明，二甲双胍可能抑制炎症并增加紧密连接蛋白表达，这可能改善血脑屏障功能并减轻CLP诱导的脑损伤。因此，未来应考虑二甲双胍在脓毒症中的潜在有益作用。
