| 杜俊凯,关 红,李治延,徐之超,白立曦,谢万科.β-谷甾醇对创伤性脑损伤大鼠的保护作用及对铁死亡-脂质代谢途径的影响[J].现代生物医学进展英文版,2024,(1):38-45. |
| β-谷甾醇对创伤性脑损伤大鼠的保护作用及对铁死亡-脂质代谢途径的影响 |
| Protective Effects of β-sitosterol on Traumatic University and its Effect on Ferroptosis-lipid Metabolism Pathway in Rats |
| Received:May 28, 2023 Revised:June 25, 2023 |
| DOI：10.13241/j.cnki.pmb.2024.01.007 |
| 中文关键词: 创伤性脑损伤 β-谷甾醇 铁死亡 脂质代谢 氧化应激 |
| 英文关键词: Traumatic brain injury β-sitosterol Ferroptosis Lipid metabolism Oxidative stress |
| 基金项目:陕西省自然科学基金项目（2018JM7152） |
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| 中文摘要: |
| 摘要 目的：揭示β-谷甾醇（Sito）对创伤性脑损伤（TBI）大鼠的保护作用及对铁死亡-脂质代谢途径的影响。方法：将大鼠分为Sham组（n=10）、TBI组（n=11）、TBI+10Sito组（n=10）、TBI+20Sito组（n=10）、TBI+40Sito组（n=10）和TBI+40Sito+GPX4-IN-3组（n=10）。Sham组大鼠不进行造模，其他组大鼠为TBI模型大鼠。Sham组和TBI组大鼠每天灌胃1 mL0.5%羧甲基纤维素钠。TBI+10Sito组、TBI+20Sito组、TBI+40Sito组大鼠分别灌胃1 mL 10、20、40 mg/kg/d的β-谷甾醇。TBI+40Sito+GPX4-IN-3组大鼠同时灌胃0.5 mL 40 mg/kg/d的β-谷甾醇和0.5 mL 15 mg/kg/d的GPX4-IN-3（铁死亡选择性诱导剂）。各组大鼠均给药14 d。给药结束后，检测了各组大鼠的神经功能评分。通过Morris水迷宫实验评价认知功能。通过蔗糖偏好实验和旷场实验评价行为学。检测血清脂质代谢指标[总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）、高密度脂蛋白胆固醇（HDL-c）]水平、脑组织含水量、脑组织氧化应激指标[超氧化物歧化酶（SOD）和丙二醛（MDA）]水平、脑组织Fe2+含量。通过苏木素伊红（HE）染色和尼氏染色评价脑组织损伤。通过Western blot和免疫荧光染色检测谷胱甘肽过氧化物酶4（GPX4）蛋白表达。结果：与Sham组比较，TBI组大鼠的神经功能评分和逃避潜伏期升高，穿越平台次数、蔗糖偏好率、水平活动分数和垂直活动分数降低，TC、TG和LDL-c升高，HDL-c降低，脑组织含水量升高，神经元出现明显损伤，SOD水平降低，MDA水平升高，Fe2+含量升高，GPX4蛋白表达水平和GPX4相对荧光强度降低（P<0.05）。与TBI组比较，TBI+10Sito组、TBI+20Sito组和TBI+40Sito组大鼠的神经功能评分和逃避潜伏期降低，穿越平台次数、蔗糖偏好率、水平活动分数和垂直活动分数升高，TC、TG和LDL-c降低，HDL-c升高，脑组织含水量降低，神经元损伤明显减轻，SOD水平升高，MDA水平降低，Fe2+含量降低，GPX4蛋白表达水平和GPX4相对荧光强度升高（P<0.05）。与TBI+40Sito组比较，TBI+40Sito+GPX4-IN-3组大鼠的神经功能评分和逃避潜伏期升高，穿越平台次数、蔗糖偏好率、水平活动分数和垂直活动分数降低，TC、TG和LDL-c升高，HDL-c降低，脑组织含水量升高，神经元损伤加重，SOD水平降低，MDA水平升高，Fe2+含量升高，GPX4蛋白表达水平和GPX4相对荧光强度降低（P<0.05）。结论：β-谷甾醇可有效减轻TBI后的继发性损伤，其机制可能与抑制铁死亡途径介导的氧化应激和脂质代谢紊乱有关。 |
| 英文摘要: |
| ABSTRACT Objective: To reveal the protective effect of β-sitosterol (Sito) on traumatic brain injury (TBI) rats and its effect on ferroptosis-lipid metabolism pathway. Methods: Rats were divided into Sham group (n=10), TBI group (n=11), TBI+10Sito group (n=10), TBI+20Sito group (n=10), TBI+40Sito group (n=10) and TBI+40Sito+GPX4-IN-3 group (n=10). The rats in Sham group were not modeled, while the rats in other groups were TBI model rats. Rats in Sham group and TBI group were given 1 mL 0.5% carboxymethyl cellulose sodium by gastric gavage every day. Rats in TBI+10Sito group, TBI+20Sito group and TBI+40Sito group were given intragastric administration of β-sitosterol of 1 mL 10, 20 and 40 mg/kg/d respectively. Rats in TBI+40Sito+GPX4-IN-3 group were given intragastric administration of β-sitosterol of 0.5 mL 40 mg/kg/d and GPX4-IN-3 of 0.5 mL 15 mg/kg/d (selective inducer of ferroptosis). Rats in each group were given drugs for 14 days. At the end of administration, the neurological function scores of rats in each group were measured. Cognitive function was evaluated by Morris water maze test. Behavior was evaluated by sucrose preference test and open field experiment. The levels of serum lipid metabolism indexes [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c)], brain water content, brain oxidative stress indexes [superoxide dismutase (SOD) and malondialdehyde (MDA)] and brain tissue Fe2+ content were measured. Brain injury was evaluated by hematoxylin-eosin (HE) staining and Nissl staining. The protein expression of glutathione peroxidase 4 (GPX4) was detected by Western blot and immunofluorescence staining. Results: Compared with Sham group, the neurological function score and escape latency increased, the number of crossing platform, sucrose preference rate, horizontal activity score and vertical activity score decreased, TC, TG and LDL-c increased, HDL-c decreased, brain water content increased, neurons showed obvious damage, SOD level decreased, MDA level increased, Fe2+ content increased, GPX4 protein expression and GPX4 relative fluorescence intensity decreased in TBI group (P<0.05). Compared with TBI group, neurological function score and escape latency decreased, the number of crossing platform, sucrose preference rate, horizontal activity score and vertical activity score increased, TC, TG and LDL-c decreased, HDL-c increased, brain water content decreased, neuronal injury was significantly alleviated, SOD level increased, MDA level decreased, Fe2+ content decreased, GPX4 protein expression and GPX4 relative fluorescence intensity increased in TBI+10Sito group, TBI+20Sito group and TBI+40Sito group (P<0.05). Compared with TBI+40Sito group, the neurological function score and escape latency increased, the number of crossing platform, sucrose preference rate, horizontal activity score and vertical activity score decreased, TC, TG and LDL-c increased, HDL-c decreased, brain water content increased, neuron injury aggravated, SOD level decreased, MDA level increased, Fe2+ content increased, GPX4 protein expression and GPX4 relative fluorescence intensity decreased in TBI+40Sito+GPX4-IN-3 group (P<0.05). Conclusion: β-sitosterol can effectively reduce the secondary injury after TBI, and its mechanism may be related to the inhibition of oxidative stress and lipid metabolism disorder mediated by ferroptosis pathway. |
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