Department of Anesthesiology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu, China.
Hum Exp Toxicol. 2020 Jun;39(6):816-827. doi: 10.1177/0960327119897103. Epub 2020 Jan 21.
The repairing effect and potential mechanism of miR-137 on cerebral ischemic injury in rats was investigated. The volume of cerebral infarction and calculated brain water content was detected by triphenyltetrazolium chloride staining. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay. The pathological damage of brain tissue was analyzed by hematoxylin and eosin and Nissl staining. The apoptosis in ischemic brain tissue was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The levels of STAT1 and JAK1 proteins were analyzed by Western blot. The expression of miR-137 in primary hippocampal neurons was detected by reverse transcription polymerase chain reaction. miR-137 overexpression significantly improved brain damage in rats. miR-137 overexpression can reduce the expression of TNF-α, IL-1β, and IL-6. miR-137 overexpression can reduce the degree of brain tissue damage and inhibit the expression of JAK1 and STAT1 proteins. miR-137 overexpression can reduce oxygen-glucose deprivation (OGD)/R-induced cell damage, improve cell proliferation, and reduce apoptotic rate. JAK1 and STAT1 protein expression was inhibited in hippocampal neurons after OGD/R treatment after transfection with miR-137 mimic. After the addition of the Filgotinib inhibitor, the levels of JAK1 and STAT1 proteins were significantly reduced. The results suggested that miR-137 overexpression can effectively improve ischemic injury after focal cerebral ischemia and protect against by inhibiting JAK1/STAT1 pathway.
研究了 miR-137 对大鼠脑缺血损伤的修复作用及其潜在机制。通过氯化三苯基四氮唑染色检测脑梗死体积和计算脑水含量。通过酶联免疫吸附试验检测炎症因子的表达。通过苏木精-伊红和尼氏染色分析脑组织的病理损伤。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记法检测缺血性脑组织中的细胞凋亡。通过 Western blot 分析 STAT1 和 JAK1 蛋白水平。通过逆转录聚合酶链反应检测原代海马神经元中 miR-137 的表达。miR-137 过表达显著改善了大鼠的脑损伤。miR-137 过表达可以降低 TNF-α、IL-1β 和 IL-6 的表达。miR-137 过表达可以减轻脑组织损伤程度并抑制 JAK1 和 STAT1 蛋白的表达。miR-137 过表达可以减少氧葡萄糖剥夺（OGD）/R 诱导的细胞损伤，促进细胞增殖，降低细胞凋亡率。OGD/R 处理后转染 miR-137 模拟物可抑制海马神经元中 JAK1 和 STAT1 蛋白的表达。加入 Filgotinib 抑制剂后，JAK1 和 STAT1 蛋白水平显著降低。结果表明，miR-137 过表达可通过抑制 JAK1/STAT1 通路有效改善局灶性脑缺血后的缺血性损伤并发挥保护作用。
