| 刘红旗,丁丰,何思源.隐丹参酮调节鞘氨醇激酶 1/1磷酸鞘氨醇信号通路对脑梗死大鼠神经元凋亡的影响[J].安徽医药,2025,29(9):1739-1744. |
| 隐丹参酮调节鞘氨醇激酶 1/1磷酸鞘氨醇信号通路对脑梗死大鼠神经元凋亡的影响 |
| Effect of cryptotanshinone on neuronal apoptosis in rats with cerebral infarction by regulating the sphingosine kinase 1/sphingosine-1 phosphate signaling pathway |
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| DOI:10.3969/j.issn.1009-6469.2025.09.009 |
| 中文关键词: 脑梗死 隐丹参酮 神经元凋亡 鞘氨醇激酶 1 1磷酸鞘氨醇 |
| 英文关键词: Cerebral infarction Cryptotanshinone Neuron apoptosis Sphingosine kinase 1 Sphingosine-1 phosphate |
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| 中文摘要: |
| 目的探究隐丹参酮( CPT)调节鞘氨醇激酶 1(Sphk1)/1磷酸鞘氨醇( S1P)对脑梗死大鼠神经元凋亡的影响。方法 2023年 1―3月构建脑梗死大鼠模型,将造模成功的大鼠采用随机数字表法分为模型组、 CPT低剂量组、 CPT中剂量组、 CPT高剂量组、 CPT高剂量 +佛波酯( PMA)组,每组 15只。另取 15只大鼠作为假手术组。对 6组大鼠进行神经功能缺损评估, 5-氯化三苯基四氮唑( TTC)染色观察脑梗死体积,苏木精 -伊红(HE)染色观察 CA1区脑组织神经元变化,原位末端标记(TUNEL)法检测 CA1区脑组织神经元凋亡, Fluoro-Jade C(F-JC)染色检测 CA1区脑组织神经元损伤,免疫荧光染色检测 CA1区脑组织 Sphk1、S1P表达,蛋白质印迹法检测脑组织 Sphk1、S1P1、Bcl-2、Bax蛋白表达。结果与假手术组[( 0±0)分、(0±0)%、(3.25±0.49)%、(25.83±2.82)mm2]相比,模型组大鼠神经功能缺损评分( 2.71±0.29)分、脑梗死率( 34.57±3.86)%、神经元细胞凋亡率(38.14±4.25)%、F-JC阳性细胞数( 408.13±32.5)mm2、Sphk1、S1P、Bax表达明显升高, Bcl-2蛋白表达明显降低( P<0.05)神经元细胞明显受损;与模型组相比, CPT低、中、高剂量组大鼠神经功能缺损评分、脑梗死率、神经元细胞凋亡率、 F-JC阳性细,胞数、 Sphk1、S1P、Bax表达明显降低, Bcl-2蛋白表达明显升高( P<0.05),神经元细胞损伤改善;与 CPT高剂量组相比, CPT高剂量 +PMA组大鼠神经功能缺损评分、脑梗死率、神经元细胞凋亡率、 F-JC阳性细胞数、 Sphk1、S1P、Bax表达明显升高, Bcl-2蛋白表达明显降低( P<0.05),神经元细胞损伤加重。结论 CPT可能通过抑制 Sphk1/S1P信号通路,改善脑梗死大鼠神经功能,减少梗死体积和神经元凋亡。 |
| 英文摘要: |
| Objective To investigate the effect of cryptotanshinone (CPT) on neuronal apoptosis in rats with cerebral infarction byregulating sphingosine kinase 1 (Sphk1)/sphingosine-1 phosphate (S1P).Methods The rat model of cerebral infarction was construct-ed from January to March 2023, and the successfully modeled rats were randomly grouped into model group, low dose CPT group, medi-um dose CPT group, high dose CPT group, and high dose CPT+phorbol 12-myristate 13-acetate (PMA) group, with 15 rats in eachgroup. Another 15 rats were collected as the sham operation group. Rats in the six groups were evaluated for neurological deficits, 5-tri-phenyl tetrazolium chloride (TTC) staining was applied to observe the volume of cerebral infarction, hematoxylin eosin (HE) stainingwas applied to observe neuronal changes in the CA1 region of the brain tissue, terminaldeoxynucleotidly transferase mediated labelling(TUNEL) method was applied to detect neuronal apoptosis in brain tissue of CA1 region, Fluoro-Jade C (F-JC) staining was applied todetect neuronal damage in brain tissue of CA1 region, immunofluorescence staining was applied to detect the expression of Sphk1 andS1P in brain tissue of CA1 region, protein blotting was applied to detect the expression of Sphk1, S1P1, Bcl-2, and Bax proteins in brain tissue.Results Compared with the sham surgery group [(0±0) scores,(0±0)%,(3.25±0.49)%, (25.83±2.82) mm2], the neurological deficit score, cerebral infarction rate, neuronal apoptosis rate, F-JC positive cell count, and the expression of Sphk1, S1P, and Bax in the model group were greatly increased, the expression of Bcl-2 protein was greatly reduced (P<0.05), neuron cells were obviously dam-aged; compared with the model group, the neurological deficit score (2.71±0.29), cerebral infarction rate (34.57±3.86)%, neuronal apop-tosis rate (38.14±4.25)%, F-JC positive cell count (408.13±32.5) mm2, and the expression of Sphk1, S1P, and Bax in the low, medium,and high dose CPT groups were obviously reduced, the expression of Bcl-2 protein was obviously increased (P<0.05), neuronal cell damage improved; compared with the high-dose CPT group, the neurological deficit score, cerebral infarction rate, neuronal apoptosis rate, F-JC positive cell count, and the expression of Sphk1, S1P, and Bax in the CPT high-dose+PMA group were greatly increased, the expression of Bcl-2 protein was greatly reduced (P<0.05), neuron cell damage worsened.Conclusion CPT may improve neural func-tion, reduce infarct volume and neuronal apoptosis in rats with cerebral infarction by inhibiting the Sphk1/S1P signaling pathway. |
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