| 徐梅,汪砚雨,李晓玲,等.雷公藤甲素对感染性休克大鼠脑组织的保护及对TLR4/Myd88信号通路的调控[J].浙江中医药大学学报,2021,45(7):732-738, 743. |
| 雷公藤甲素对感染性休克大鼠脑组织的保护及对TLR4/Myd88信号通路的调控 |
| Protective Effect of Triptolide on Brain Tissue of Septic Shock Rats and Its Regulation of TLR4/Myd88 Signaling Pathway |
| DOI：10.16466/j.issn1005-5509.2021.07.008 |
| 中文关键词: 雷公藤甲素 感染性休克 氧化应激 炎症反应 病理变化 Toll样受体4 髓样分化因子88 核转录因子-κB |
| 英文关键词: triptolide septic shock oxidative stress inflammatory response pathological changes Toll-like receptor 4 myeloid differentiation factor 88 nuclear transcription factor-κB |
| 基金项目:河南省高等学校重点科研项目(18B150021) |
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| 中文摘要: |
| [目的]研究雷公藤甲素(triptolide，TL)对感染性休克(septic shock，SS)大鼠脑组织的保护作用，并探讨相关机制。[方法]从80只无特定病原体(specific pathogen free，SPF)级SD大鼠中随机抽取15只，仅剖腹不结扎盲肠及穿孔，设为正常组；其余65只随机分为SS组，TL低、高剂量组和阳性药物组，以盲肠结扎穿孔法建立SS模型。TL低、高剂量组建模前1h分别以TL 200、400μg·kg-1灌胃；阳性药物组以地塞米松10mg·kg-1灌胃；正常组与SS组予等量0.9%氯化钠溶液灌胃。建模后12h检测脑组织含水量；检测脑组织超氧化物歧化酶(superoxide dismutase，SOD)活性和丙二醛(malondialdehyde，MDA)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)、白介素-1β(interleukin-1β，IL-1β)含量；苏木精-伊红(hematoxylin-eosin，HE)染色观察海马CA1区病理学形态变化，Nissl染色观察海马CA1区神经元形态、数量；Western blot检测脑组织Toll样受体4(Toll like receptor 4，TLR4)、髓样分化因子88(myeloid differentiation factor 88，MyD88)、核转录因子-κB(nuclear transcription factor-κB，NF-κB)、磷酸化核转录因子-κB(phospho-nuclear transcription factor-κB，p-NF-κB)蛋白相对表达量。[结果]与正常组比较，SS组脑组织含水量、MDA、TNF-α、IL-1β含量增加，脑组织SOD活性减低，TLR4、MyD88蛋白相对表达量及p-NF-κB p65/NF-κB p65均升高(P＜0.05)；与SS组比较，TL低、高剂量组，阳性药物组脑组织含水量、MDA、TNF-α、IL-1β含量减少，脑组织SOD活性增加，TLR4、MyD88蛋白相对表达量及p-NF-κB p65/NF-κB p65均降低(P＜0.05)；与TL低剂量组比较，TL高剂量组、阳性药物组脑组织含水量、MDA、TNF-α、IL-1β含量减少，脑组织SOD活性增加，TLR4、MyD88蛋白相对表达量及p-NF-κB p65/NF-κB p65降低(P＜0.05)。HE染色显示，SS组细胞体积缩小、数量减少、排列紊乱，多数发生空泡样改变及死亡；TL低、高剂量组及阳性药物组多数细胞边界清晰，排列较整齐，少数萎缩、深染、空泡变性。Nissl染色显示，SS组细胞排列稀疏，边缘模糊，染色浅，神经元数目减少，胞质中尼氏体数量明显减少；TL低、高剂量组，阳性药物组神经元数量增加，染色较清晰，胞质中尼氏体数量增加。[结论] TL可减轻SS大鼠脑组织水肿，减轻氧化应激及炎症反应，改善脑组织病理变化，保护神经元，其作用机制可能与抑制TLR4/MyD88信号通路相关蛋白表达有关。 |
| 英文摘要: |
| [Objective] To study the protective effect of triptolide(TL) on the brain tissue of septic shock(SS) rats， and to explore the related mechanisms. [Methods] Fifteen specific pathogen free(SPF) SD rats were randomly selected from 80 rats for laparotomy， without ligation and perforation of the cecum， and set as normal group. The remaining 65 rats were randomly divided into SS group， TL low and high dose groups， and positive drug group. SS model was established by cecal ligation and perforation method. The TL low and high dose groups were given TL 200 and 400μg·kg-1 respectively 1 hour before modeling. The positive drug group was given dexamethasone 10mg·kg-1. The normal group and the SS group were given the same amount of 0.9% sodium chloride solution. Brain tissue water content was detected 12h after modeling. The brain tissue superoxide dismutase(SOD) activity and malondialdehyde(MDA)， tumor necrosis factor-α(TNF-α)， interleukin-1β(IL-1β) content were detected. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in the hippocampal CA1 area. Nissl staining was used to observe the changes in the morphology and number of neurons in the hippocampal CA1 area. Western blot was used to detect the brain tissue Toll-like receptor 4(TLR4)， myeloid differentiation factor 88(MyD88)， nuclear transcription factor-κB(NF-κB) and phospho-nuclear transcription factor-κB(p-NF-κB) protein expression. [Results] Compared with normal group， the brain tissue water content， MDA， TNF-α， IL-1β content， the relative expression of TLR4， MyD88 protein， p-NF-κB p65/NF-κB p65 in SS group were all increased(P＜0.05)， while the SOD activity of brain tissue was decreased(P＜0.05). Compared with SS group， the brain tissue water content， MDA， TNF-α， IL-1β content， the relative expression of TLR4， MyD88 protein， p-NF-κB p65/NF-κB p65 in TL low and high dose group， and positive drug group were all decreased(P＜0.05)， while the SOD activity of brain tissue was increased(P＜0.05). Compared with TL low dose group， the brain tissue water content， MDA， TNF-α， IL-1β content， the relative expression of TLR4， MyD88 protein， p-NF-κB p65/NF-κB p65 in TL high dose group， and positive drug group were all decreased(P＜0.05)， while the SOD activity of brain tissue was increased(P＜0.05). The results of HE staining showed that the cell volume of SS group was reduced， the number was reduced， and the arrangement was disordered， and most of the cells had vacuole-like changes and death; while in TL low dose and high dose groups and positive drug group， the majority of the cells had clear boundaries and neat arrangement， with a few cells atrophy， deep dyeing， vacuole degeneration. The results of Nissl staining showed that the cells in SS group were sparsely arranged， blurred edges， lightly stained， and the number of neurons was reduced， and the number of Nissl bodies in the cytoplasm was significantly reduced; the number of neurons in TL low and high dose groups and positive drug group increased， and the staining was clearer， the number of Nissl bodies in the cytoplasm increased. [Conclusion] TL can reduce brain edema in SS rats， reduce oxidative stress and inflammation， improve brain pathological changes， and protect neurons. Its mechanism may be related to inhibiting the expression of TLR4/MyD88 signaling pathway-related proteins. |
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