| 邹树峰,姜碧霞,冯九庚,等.人参皂甙-Rb1通过促进神经元线粒体自噬治疗大鼠创伤性颅脑损伤的机制[J].浙江中医药大学学报,2022,46(10):1063-1069. |
| 人参皂甙-Rb1通过促进神经元线粒体自噬治疗大鼠创伤性颅脑损伤的机制 |
| The Mechanism of Ginsenoside-Rb1 in Treating Traumatic Brain Injury Rats by Promoting Mitophagy |
| DOI：10.16466/j.issn1005-5509.2022.10.002 |
| 中文关键词: 线粒体自噬 人参皂甙Rb1 凋亡 氧化应激 创伤性颅脑损伤 神经功能 形态损伤 |
| 英文关键词: mitophagy GS-Rb1 apoptosis oxidative stress TBI nerve function morphological damage |
| 基金项目:江西省科技厅重点研发项目(20203BBGL73172、20192BBGL7022)；江西省杰出青年项目(20202ACBL216005)；江西省教育厅科研项目(GJJ200165、GJJ190022)；国家自然科学基金项目(82171366、81960236)；江西省卫健委科研项目(20203139) |
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| 中文摘要: |
| [目的] 观察人参皂甙-Rb1(ginsenoside-Rb1，GS-Rb1)对大鼠创伤性颅脑损伤(traumatic brain injury，TBI)的治疗作用与神经元线粒体自噬激活的关系。[方法] 将80只体质量350～400 g的SD雄性大鼠随机分为假手术组、TBI组、治疗(TBI+GS-Rb1)组和自噬阻断[TBI+GS-Rb1+6-氨基-3-甲基嘌呤(3-methyladenine，3-MA)]组，每组20只。以液压打击仪建立TBI模型，根据上述分组，分别给予腹腔注射GS-Rb1及自噬抑制剂3-MA。每组选10只大鼠进行行为学检测，并以苏木精-伊红(hematoxylin-eosin， HE)染色行神经元形态学检测。其余10只分离海马区皮质，以免疫印迹法检测自噬相关轻链蛋白3-Ⅱ/轻链蛋白3-Ⅰ(light chain 3-Ⅱ/ light chain 3-Ⅰ，LC3-Ⅱ/ LC3-Ⅰ)、自噬接头蛋白(sequestosome-1，P62)、线粒体功能相关蛋白过氧化物酶体增殖物激活受体γ辅激活子-1 alpha(peroxisome proliferators-activated receptor γ coactivator-1 alpha，PGC-1α)、线粒体外膜转位蛋白20(translocase of outer mitochondrial membrane 20，TOM20)及凋亡相关蛋白B细胞淋巴瘤-2基因相关X蛋白(B cell lymphoma-2 associated X protein，Bax)、裂解的半胱天冬酶3(cleaved-cysteinyl aspartate specific proteinase 3，cleaved-caspase 3)的表达；采用黄嘌呤氧化酶法、硫酸代巴比妥法、二硫代硝基苯甲酸缩合法分别检测氧化应激相关因子超氧物歧化酶(superoxide dismutase，SOD)活性、丙二醛(malondialdehyde，MDA)及谷胱甘肽(glutathione，GSH)水平。[结果] 与TBI组比较，治疗组神经损伤严重程度评分(neurological severity score，NSS)明显下降(P＜0.05)，神经元损伤程度明显缓解，自噬相关蛋白LC3-Ⅱ/ LC3-Ⅰ比例明显升高，而P62表达明显降低，线粒体功能及结构相关蛋白PGC-1α、TOM20则明显升高，MDA水平明显降低，而SOD和GSH则呈相反趋势(P＜0.05)，凋亡促进因子Bax及cleaved-caspase 3表达明显降低(P＜0.05)。采用自噬抑制剂3-MA可明显抑制GS-Rb1对TBI后神经功能及形态损伤的治疗效应(P＜0.05)。[结论] GS-Rb1可能通过促进神经元线粒体自噬，抑制凋亡途径，从而保护神经元，以起到对TBI的治疗作用。 |
| 英文摘要: |
| [Objective] To observe the relationship between therapeutic effect of ginsenoside-Rb1(GS-Rb1) on traumatic brain injury(TBI) rats and the activation of neuronal mitophagy. [Methods] Eighty male SD rats weighted 350～400 g were randomly divided into 4 groups， sham surgery(Sham) group， TBI group， treatment(TBI+GS-Rb1) group， autophagy block[TBI+GS-Rb1+6-amino-3-methypurine(3-MA)] group， with 20 in each group. The TBI model was established by using the hydraulic percussion instrument， GS-Rb1 and autophagy inhibitor 3-MA were given by intraperitoneal injection according to above groups. Half rats in each group underwent behavioral detection with neurological severity score(NSS) and hematoxylin-eosin(HE) staining was used for pathological observation of neuron 48 h after TBI. Another half of rats were sacrificed and hippocampal cortex was obtained for Western blot for detecting autophagy related proteins light chain3-Ⅱ(LC3-Ⅱ)， LC3-Ⅰ， sequestosome-1(P62)， mitochondrial function and structure related proteins peroxisome proliferators-activated receptor γ coactivator-1 alpha(PGC-1α)， translocase of outer mitochondrial membrane 20(TOM20)， apoptosis related proteins B cell lymphoma-2 associated X protein(Bax)， cleaved-cysteinyl aspartate specific proteinase 3(cleaved-caspase 3)， and by the methods of xanthine oxidase， sulfuric acid barbital， disulfide generation nitro benzoic acid condensation respectively to measure oxidative stress related factors superoxide dismutase(SOD) activity， malondialdehyde(MDA) and glutathione(GSH) levels. [Results] Compared with TBI group， ratio of LC3-Ⅱ/LC3-Ⅰ， PGC-1α， TOM20， SOD and GSH in treatment group were up-regulated significantly(P＜0.05)； on the contrary， NSS， the levels of P62， Bax， cleaved-caspase 3 and MDA were significantly down-regulated in each treatment group(P＜0.05). Nevertheless， autophagy inhibitor 3-MA was proved that it can inhibit above protective effects of GS-Rb1(P＜0.05). [Conclusion] GS-Rb1 may inhibit the oxidative stress and apoptosis which can alleviate the cerebral injuries in morphology and function after TBI by promoting neuronal mitophagy. |
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