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1.贵阳市妇幼保健院/贵阳市儿童医院药学部,贵阳 550003
2.贵州医科大学天然药物资源优效利用重点实验室,贵阳 561113
3.贵州医科大学药学院,贵阳 561113
主管药师。研究方向:中医药防治糖尿病。E-mail:1329070275@qq.com
教授,博士生导师,博士。研究方向:心血管药物药理活性、中药与民族药。E-mail:shengxiangchun@126.com
纸质出版日期:2024-02-15,
收稿日期:2023-08-07,
修回日期:2023-12-24,
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杨红,任鹏艳,陈永鑫等.1,8-桉叶油素对2型糖尿病胰岛β细胞铁死亡的干预作用及机制 Δ[J].中国药房,2024,35(03):290-295.
YANG Hong,REN Pengyan,CHEN Yongxin,et al.Interventional effect and mechanism of 1,8-cineoleon pancreatic β cell ferroptosis induced by type 2 diabetes[J].ZHONGGUO YAOFANG,2024,35(03):290-295.
杨红,任鹏艳,陈永鑫等.1,8-桉叶油素对2型糖尿病胰岛β细胞铁死亡的干预作用及机制 Δ[J].中国药房,2024,35(03):290-295. DOI: 10.6039/j.issn.1001-0408.2024.03.05.
YANG Hong,REN Pengyan,CHEN Yongxin,et al.Interventional effect and mechanism of 1,8-cineoleon pancreatic β cell ferroptosis induced by type 2 diabetes[J].ZHONGGUO YAOFANG,2024,35(03):290-295. DOI: 10.6039/j.issn.1001-0408.2024.03.05.
目的
2
研究1,8-桉叶油素对2型糖尿病胰岛β细胞铁死亡的干预作用及机制。
方法
2
使用高糖作用于小鼠胰岛β细胞以建立细胞铁死亡模型,考察低、高剂量1,8-桉叶油素(0.25、0.5 μmol/L)对胰岛β细胞中Fe
2+
水平的影响,并考察1,8-桉叶油素(0.5 μmol/L)联合铁死亡诱导剂Erastin(20 μmol/L)和抑制剂Ferrostatin-1(20 μmol/L)后对胰岛β细胞中谷胱甘肽过氧化物酶4(GPX4)、环氧合酶2(COX2)蛋白表达的影响。采用高脂高糖饲料饲养联合腹腔注射链脲佐菌素构建2型糖尿病小鼠模型,考察低、高剂量1,8-桉叶油素(50、200 mg/kg)对模型小鼠胰腺组织病理形态、铁含量以及GPX4、COX2蛋白表达的影响。
结果
2
细胞实验结果显示,与模型组比较,经1,8-桉叶油素干预后,胰岛β细胞中Fe
2+
水平显著降低(
P
<0.05);GPX4蛋白表达水平显著升高(
P
<0.05),COX2蛋白表达水平显著降低(
P
<0.05),且联合Ferrostatin-1后上述两种蛋白表达趋势相同,而联合Erastin后差异无统计学意义。动物实验结果显示,与模型组比较,经1,8-桉叶油素干预后,小鼠胰岛结构恢复完整,形态有所改善;胰腺组织中铁含量和COX2蛋白表达水平均显著降低(
P
<0.05),GPX4蛋白表达水平显著升高(
P
<0.05)。
结论
2
1,8-桉叶油素对2型糖尿病胰岛β细胞损伤具有明显的改善作用,其作用机制可能与降低细胞内铁沉积以及调控铁死亡相关蛋白有关。
OBJECTIVE
2
To study the interventional effect and mechanism of 1,8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes.
METHODS
2
In vitro
ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1,8-cineole (0.25, 0.5 μmol/L) on the level of Fe
2+
in pancreatic β cells were investigated. The effects of 1,8-cineole (0.5 μmol/L) combined with ferroptosis inducer Erastin (20 μmol/L) and ferroptosis inhibitor Ferrostatin-1 (20 μmol/L) on the protein expressions of glutathione peroxidase-4 (GPX4) and cyclooxygenase-2 (COX2) were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1,8-cineole (50, 200 mg/kg) on the pathological morphology of pancreatic tissue, the content of iron as well as the protein expressions of GPX4 and COX2 were investigated.
RESULTS
2
The results of the cell experiment showed that compared with the model group, pretreatment with 1,8-cineole significantly reduced intracellular Fe
2+
levels and upregulated GPX4 protein expression, while downregulated COX2 protein expression in pancreatic β cells (
P
<0.05). After combining with Ferrostatin-1, the expression trends of the above two proteins were the same, while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group, after intervention with 1,8-cineole, the structure of the pancreatic islets in mice recovered intact and their morphology improved; the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly (
P
<0.05), while protein expression of GPX4 was increased significantly (
P
<0.05).
CONCLUSIONS
2
1,8-cineole could ameliorate pancreatic β cell injury induced by diabetes, the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.
1,8-桉叶油素2型糖尿病胰岛β细胞铁死亡
type 2 diabetespancreatic β cellferroptosis
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