| 引用本文: |
余文运, 王焱, 谢丹, 祝圆圆, 毛修月, 罗刚, 胡国恒.龙琥醒脑颗粒对脑出血大鼠的影响及其作用机制[J].湖南中医药大学学报,2025,45(10):1825-1830[点击复制] |
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| 龙琥醒脑颗粒对脑出血大鼠的影响及其作用机制 |
| 余文运,王焱,谢丹,祝圆圆,毛修月,罗刚,胡国恒 |
| (湖南中医药大学第一附属医院, 湖南 长沙 410007;湖南中医药大学第一中医临床学院, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨龙琥醒脑颗粒对脑出血（ICH）大鼠神经功能缺损与脑含水量的影响，并探讨其机制。方法 采用自体血注入法建立ICH大鼠模型。造模成功后采用随机数字表法将模型大鼠随机分为模型组、西药组、中药组、中西组，每组20只；另取20只为假手术组。假手术组、模型组灌胃+腹腔注射生理盐水；西药组腹腔注射3.15 mL/kg七叶皂苷钠；中药组灌胃2.5 g/kg龙琥醒脑颗粒溶液；中西组灌胃2.5 g/kg龙琥醒脑颗粒溶液+腹腔注射3.15 mL/kg七叶皂苷钠。每日2次，共干预6次。对大鼠进行改良神经功能缺损评分（m-NSS），称重法计算脑含水量，Western blot、RT-PCR检测受损脑组织PTEN诱导的丝氨酸/苏氨酸蛋白激酶1（PINK1）、E3泛素连接酶（Parkin）、微管相关蛋白1轻链3（LC3）蛋白及mRNA相对表达量。结果 与假手术组比较，模型组m-NSS评分升高（P＜0.01），各时间点（12、48、72 h）脑含水量升高（P＜0.01），PINK1、Parkin蛋白和mRNA水平升高（P＜0.05，P＜0.01），LC3-Ⅰ、LC3-Ⅱ蛋白及LC3 mRNA表达降低（P＜0.05，P＜0.01）；与模型组比较，各用药组大鼠m-NSS评分均降低（P＜0.05，P＜0.01），造模后48、72 h大鼠脑含水量降低（P＜0.05，P＜0.01），PINK1、Parkin蛋白及mRNA表达均降低（P＜0.05，P＜0.01），LC3-Ⅰ、LC3-Ⅱ蛋白和LC3 mRNA表达升高（P＜0.05，P＜0.01）；与西药组比较，中西组m-NSS评分降低（P＜0.05），72 h时中药组、中西组脑含水量降低（P＜0.05，P＜0.01），中药组、中西组PINK1、Parkin蛋白和mRNA表达降低（P＜0.05，P＜0.01），中药组LC3-Ⅱ和中西组LC3-Ⅰ、LC3-Ⅱ蛋白及两组LC3 mRNA表达均升高（P＜0.05，P＜0.01）；与中药组比较，中西组m-NSS评分降低（P＜0.05），在各时间点脑含水量均降低（P＜0.05），PINK1、Parkin蛋白和mRNA表达降低（P＜0.05，P＜0.01），LC3-Ⅰ、LC3-Ⅱ蛋白及LC3 mRNA表达升高（P＜0.05）。结论 龙琥醒脑颗粒具有保护ICH大鼠脑组织的作用,可能与其抑制PINK1、Parkin表达有关。 |
| 关键词: 脑出血 龙琥醒脑颗粒 线粒体自噬 脑出血后水肿 瘀水互结 PINK1/Parkin通路 活血利水 |
| DOI：10.3969/j.issn.1674-070X.2025.10.004 |
| 投稿时间：2025-04-08 |
| 基金项目:湖南省卫生健康委员会课题（D202304099020）；湖南省中医药管理局课题（B2023023）；长沙市自然科学基金项目（kq2208200）；湖南中医药大学校院联合基金中医药传承创新专项（2024XYLH364）。 |
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| Effects of Longhu Xingnao Granules on intracerebral hemorrhage in rats and its mechanism of action |
| YU Wenyun, WANG Yan, XIE Dan, ZHU Yuanyuan, MAO Xiuyue, LUO Gang, HU Guoheng |
| (The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The First Clinical School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the effects of Longhu Xingnao Granules (LHXNG) on neurological deficits and brain water content in rats with intracerebral hemorrhage (ICH), and to explore its mechanism. Methods An ICH rat model was established using autologous blood injection. After successful modeling, the rats were randomly divided into four groups (a model group, a Western medicine group, a Chinese medicine group, and a combined therapy group) using a random number table, with 20 rats in each group; another 20 rats served as the sham-operated group. The sham-operated and model groups received intragastric administration and intraperitoneal injection of normal saline. The Western medicine group received intraperitoneal injection of sodium aescinate (3.15 mL/kg), and the Chinese medicine group received intragastric administration of LHXNG solution (2.5 g/kg). The combined therapy group received both intragastric LHXNG solution (2.5 g/kg) and intraperitoneal injection of sodium aescinate (3.15 mL/kg). Treatments were administered twice daily, for a total of six interventions. Neurological deficits were evaluated using the modified neurological severity score (m-NSS). Brain water content was measured by the wet-dry weight method. The relative expression levels of PTEN-induced putative kinase 1 (PINK1), E3 ubiquitin ligase (Parkin), and microtubule-associated protein 1 light chain 3 (LC3) at both protein and mRNA levels in the injured brain tissue were determined by Western blot and RT-PCR, respectively. Results Compared with the sham-operated group, the model group showed significantly increased m-NSS score (P＜0.01), increased brain water content at all time points (12, 48, 72 h) (P＜0.01), upregulated expression of PINK1 and Parkin at both protein and mRNA levels (P＜0.05, P＜0.01), and downregulated protein expression of LC3-Ⅰ and LC3-Ⅱ and mRNA expression of LC3 (P＜0.05, P＜0.01). Compared with the model group, all treatment groups showed significantly decreased m-NSS scores (P＜0.05, P＜0.01), decreased brain water content at 48 and 72 h post-modeling (P＜0.05, P＜0.01), downregulated expression of PINK1 and Parkin at both protein and mRNA levels (P＜0.05, P＜0.01), and upregulated protein expression of LC3-Ⅰ and LC3-Ⅱ and mRNA expression of LC3 (P＜0.05, P＜0.01). Compared with the Western medicine group, the combined therapy group demonstrated significantly decreased m-NSS score (P＜0.05); at 72 h, both the Chinese medicine group and the combined therapy group showed significantly decreased brain water content (P＜0.05, P＜0.01), and downregulated expression of PINK1 and Parkin at protein and mRNA levels (P＜0.05, P＜0.01). The Chinese medicine group showed upregulated protein expression of LC3-Ⅱ, while the combined therapy group showed upregulated protein expression of both LC3-Ⅰ and LC3-Ⅱ; moreover, mRNA expression of LC3 was upregulated in both groups (P＜0.05, P＜0.01). Compared with the Chinese medicine group, the combined therapy group exhibited lower m-NSS score (P＜0.05), decreased brain water content at all time points (P＜0.05), downregulated expression of PINK1 and Parkin at both protein and mRNA levels (P＜0.05, P＜0.01), and upregulated protein expression of LC3-Ⅰ and LC3-Ⅱ and mRNA expression of LC3 (P＜0.05). Conclusion LHXNG exerts a protective effect on the brain tissue of rats with ICH, which may be related to its inhibition on PINK1 and Parkin expression. |
| Key words: intracerebral hemorrhage Longhu Xingnao Granules mitophagy post-hemorrhagic cerebral edema blood stasis and water retention PINK1/Parkin pathway circulating blood and draining water retention |
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