探究雷公藤红素（Cela）对创伤性脑损伤（TBI）后继发性脑伤的作用及机制。

120只健康雄性C57BL/6J小鼠按照随机数字表法分为假手术组（Sham组，36只）、颅脑创伤组（TBI组，42只）、干预组（TBI+Cela组，42只）。Sham组仅行开骨窗处理；TBI组与TBI+Cela组开骨窗后采用微处理器控制的气动冲击装置建立小鼠TBI模型，分别于术前24 h和TBI造模后0.5 h，TBI+Cela组的小鼠予以腹腔注射Cela（1 mg/kg体质量），TBI组的小鼠予以腹腔注射等量的生理盐水。TBI造模后24 h，采用尼氏染色法测定TBI后脑损伤体积；干湿重法测定脑含水量；改良神经功能缺损评分（mNSS）、转角实验及挂线实验测定TBI后脑功能的损伤程度；DHE染色法测定TBI后脑组织活性氧自由基（ROS）水平；酶联免疫吸附法测定TBI后丙二醛（MDA）、三磷酸腺苷含量以及线粒体呼吸链复合物Ⅰ~Ⅳ活性；透射电镜观察并计算TBI后线粒体超微形态改变情况；Western blotting测定TBI后SIRT3蛋白的表达水平改变情况。

TBI后24 h，TBI+Cela组的脑损伤体积、脑含水量较TBI组明显减少，差异有统计学意义（P<0.05）。TBI后小鼠神经功能明显受损，TBI+Cela组的mNSS评分较TBI组显著降低，坠落潜伏期较TBI组显著升高，向左转向的比例较TBI组明显减少，差异有统计学意义（P<0.05）。TBI后小鼠脑组织ROS、MDA水平显著升高，TBI+Cela组的ROS、MDA水平较TBI组均明显降低，差异有统计学意义（P<0.05）。TBI后线粒体形态与功能显著受损，TBI+Cela组的线粒体形态与功能损伤程度较TBI组明显好转，差异有统计学意义（P<0.05）。TBI后SIRT3的表达显著降低，TBI+Cela组中SIRT3的表达水平较TBI组明显升高，差异有统计学意义（P<0.05）。

Cela可显著减轻TBI造成的脑实质与功能损伤、氧化应激强度以及线粒体形态与功能损伤，其机制可能是通过对SIRT3的正向调控来发挥线粒体保护作用，进而减轻TBI后的氧化应激强度，最终发挥减轻TBI后继发性损伤的作用。

To investigate the effect and mechanism of celastrol (Cela) on secondary injury after traumatic brain injury (TBI).

A total of 120 healthy male C57BL/6J mice were randomly divided into Sham group (n=36), TBI group (n=42), and TBI+Cela group (n=42). The Sham group was only treated with open bone window. In TBI group and TBI+Cela group, a microprocessor controlled pneumatic impact device was used to establish the TBI model after opening the bone window. Mice in the TBI+Cela group were intraperitoneally injected with Cela (1 mg/kg body weight), while mice in the TBI group were intraperitoneally injected with the same amount of physiological saline solution. Twenty-four hours after modeling, Nissl staining was used to determine the brain injury volume after TBI. Brain water content was measured by dry-wet weight method. The degree of brain function injury after TBI was determined by modified neurological severity score (mNSS), turn Angle test and seton test. DHE staining was used to measure the level of reactive oxygen species (ROS) in brain tissue after TBI. The contents of malondialdehyde (MDA), adenosine triphosphate and the activity of mitochondrial respiratory chain complex Ⅰ-Ⅳ were measured by enzyme-linked immunosorbent assay. Transmission electron microscopy was used to observe and calculate the ultrastructural changes of mitochondria after TBI. Western blotting was used to determine the expression of SIRT3 protein after TBI.

Twenty-four hours after TBI, the brain injury volume and brain water content in the TBI+Cela group were significantly reduced than those of the TBI group, and the differences were statistically significant (P<0.05). The neurological function of mice was significantly impaired after TBI, the mNSS score of the TBI+Cela group was significantly lower than that of the TBI group, the latency to fall was significantly higher than that of the TBI group, and the proportion of left turning was significantly reduced than that of the TBI group, and the differences were statistically significant (P<0.05). The levels of ROS and MDA in mouse brain tissue were significantly increased after TBI, while the ROS and MDA levels in the TBI+Cela group were significantly lower than those in the TBI group, with statistical significance (P<0.05). The mitochondrial morphology and function were significantly impaired after TBI, and the degree of mitochondrial morphology and function damage of the TBI+Cela group were significantly improved than those of the TBI group, with statistical significance (P<0.05). The expression of SIRT3 was significantly reduced after TBI, while the expression level of SIRT3 was significantly increased in the TBI+Cela group, with statistical significance (P<0.05).

Cela can significantly reduce TBI induced brain parenchymal and functional damage, oxidative stress intensity, and mitochondrial morphological and functional damage, possibly by positively regulating SIRT3 to protect mitochondria, thereby reducing oxidative stress intensity after TBI, and ultimately alleviating secondary brain injury after TBI.