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3-乙酰基-11-酮-β乳香酸对大鼠脑缺血再灌注损伤的保护作用及其机制研究

Protective effect and mechanism of 3-acetyl-11-keto-β-boswellic acid on cerebral ischemia-reperfusion injury in rats

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【作者】 张艳王俊严永兴顾婧魏颖楠沈咏慧

【Author】 Zhang Yan;Wang Jun;Yan Yongxing;Gu Jing;Wei Yingnan;Shen Yonghui;Department of Neurology, Hangzhou Third Hospital;

【通讯作者】 严永兴;

【机构】 杭州市第三人民医院神经内科

【摘要】 目的探讨乳香提取物3-乙酰基-11-酮-β-乳香酸(AKBA)对大鼠脑缺血再灌注损伤的保护作用及其机制。方法将80只大鼠分为假手术组、模型组、低剂量组及高剂量组,每组各20只大鼠。除假手术组外,其他三组采用改良线栓方法制备大鼠大脑中动脉缺血再灌注损伤模型,低剂量组在造模成功再灌注后60 min给予腹腔注射10 mg/kg的AKBA,高剂量组则给予20 mg/kg的AKBA。测定并计算各组大鼠脑梗死率及梗死区细胞凋亡率;采用转录实时荧光定量PCR检测微RNA-320(miRNA-320)和胰岛素样生长因子1(IGF-1)的信使RNA(mRNA)表达水平,采用Western-blotting测定脑组织IGF-1的蛋白表达情况。结果各组大鼠脑梗死率、细胞凋亡率、miRNA-320、IGF-1的mRNA及蛋白表达水平比较,差异均有统计学意义(F=193.300、230.000、100.900、180.400、26.180,P均<0.001)。进一步两两比较发现,与假手术组比较,模型组大鼠的细胞凋亡率、miRNA-320、IGF-1的mRNA及蛋白表达水平均显著升高(P均<0.05);与模型组比较,低剂量组及高剂量组大鼠的脑梗死率、细胞凋亡率及miRNA-320表达水平均显著降低,IGF-1的mRNA及蛋白表达水平均显著升高(P均<0.05)。结论 AKBA对大鼠脑缺血再灌注损伤有明显的保护作用,其机制可能是通过抑制miRNA-320的表达水平及上调IGF-1的水平来减少神经细胞的凋亡。

【Abstract】 Objective To investigate the protective effect and mechanism of 3-acetyl-11-keto-β-boswellic acid(AKBA) on cerebral ischemia-reperfusion injury in rats. Methods A total of 80 rats were randomly divided into a sham operation group, a model group, a low-dose group and a high-dose group, with 20 rats in each group. Except for the sham operation group, a middle cerebral artery ischemia-reperfusion injury model was induced by a modified suture method in the other three groups. The rats in the low-dose group were given an intraperitoneal injection of 10 mg/kg AKBA at 60 min after successful reperfusion, while the rats in the highdose group were given 20 mg/kg AKBA. The rates of cerebral infarction and apoptosis were measured and calculated in the four groups. The messenger RNA(mRNA) expression of microRNA-320(miRNA-320) and insulin-like growth factor-1(IGF-1) was detected by reverse transcription real-time fluorescence quantitative PCR, and the protein expression of IGF-1 was measured by Western-blotting. Results The cerebral infarction rate, apoptosis rate, miRNA-320 mRNA, IGF-1 m RNA and IGF-1 protein among the four groups all showed significant differences(F =193.300, 230.000, 100.900, 180.400, 26.180; all P < 0.001). Further pairwise comparison revealed that the apoptosis rate, mi RNA-320 m RNA, IGF-1 m RNA and IGF-1 protein in the model group were much higher than those in the sham operation group(all P < 0.05). The rates of cerebral infarction and apoptosis and the expression of mi RNA-320 m RNA were much lower,while the expression of IGF-1 m RNA and protein was much higher in the low-dose group and high-dose group than in the model group(all P < 0.05). Conclusion AKBA has an obvious protective effect on cerebral ischemia-reperfusion injury in rats, and it may be to reduce neuronal apoptosis by inhibiting mi RNA-320 and up-regulating IGF-1.

【基金】 浙江省中医药科学研究基金项目(2019ZA094);杭州市医药卫生科技计划项目(0020190465、A20200219)
  • 【文献出处】 中华危重症医学杂志(电子版) ,Chinese Journal of Critical Care Medicine(Electronic Edition) , 编辑部邮箱 ,2021年06期
  • 【分类号】R743.3
  • 【下载频次】167
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