目的 探讨丹膝颗粒对脑缺血再灌注损伤大鼠的保护作用及机制。方法 采用改良线栓法复制大脑中动 脉短暂阻塞（tMCAO）再灌注大鼠模型。将 SD 大鼠随机分为假手术组、模型组、尼莫地平组（10.8 mg·kg-1 ）及丹 膝颗粒低、中、高剂量组（2.7、8.1、16.2 g·kg-1 ），每组 12 只。再灌注 24 h 后，给药组灌胃给药，每日 1 次， 连续 14 d。在造模 24 h 后及给药结束后进行大鼠神经功能缺损评分；采用 TTC 染色法测量脑梗死面积；HE 染色法观察脑组织病理学变化；检测血清中白细胞介素 1β（IL-1β）、肿瘤坏死因子 α（TNF-α）、超氧化物歧化 酶（SOD）、谷胱甘肽（GSH）水平及脑组织中还原型辅酶Ⅱ（NADPH）含量；Western Blot 法检测脑组织中烟酰胺 磷酸核糖基转移酶（NAMPT）、多聚 ADP 核糖聚合酶 1（PARP1）蛋白表达水平。结果 与假手术组比较，模型 组大鼠的神经功能缺损评分显著升高（P＜0.001）；脑梗死面积显著增加（P＜0.001）；血清 IL-1β、TNF-α 水平 显著升高（P＜0.01，P＜0.001），SOD、GSH 水平显著降低（P＜0.001）；缺血侧脑组织中 NADPH 含量及 NAMPT 蛋白表达水平显著升高（P＜0.001），PARP1 蛋白表达显著下调（P＜0.01）。与模型组比较，各给药组大 鼠的神经功能缺损评分均显著降低（P＜0.05，P＜0.001）；丹膝颗粒中、高剂量组及尼莫地平组大鼠的脑梗死 面积均显著缩小（P＜0.01，P＜0.001）；丹膝颗粒中剂量组及尼莫地平组大鼠的血清 IL-1β、TNF-α 水平显著 降低（P＜0.01，P＜0.001），SOD、GSH 水平显著升高（P＜0.05，P＜0.01，P＜0.001），缺血侧脑组织中 NADPH 含量及 NAMPT、PARP1 蛋白表达水平均显著升高（P＜0.05，P＜0.01）。结论 丹膝颗粒能够缩小脑缺 血再灌注损伤大鼠的脑梗死面积，改善脑组织病理损伤，降低神经功能缺损评分，降低炎症因子水平，增强抗 氧化能力，其机制可能与激活 NAMPT、PARP1，维持 NAD+ 水平，从而影响 DNA 修复、炎症反应等多方面有关。

Objective To explore the protective effect of Danxi Granules on cerebral ischemia-reperfusion injury rats and its mechanism. Methods The rat model of transient middle cerebral artery occlusion（tMCAO） reperfusion was replicated by modified suture method. SD rats were randomly divided into sham operation group， model group， Nimodipine group（10.8 mg·kg-1 ） and Danxi Granules low-，medium- and high- dose groups（2.7，8.1，16.2 g·kg-1 ），with 12 rats in each group. After 24 hours of reperfusion，the administration group was given intragastric administration once a day for 14 consecutive days. The neurological deficit scores of rats were evaluated at 24 hours after modeling and at the end of administration. The area of cerebral infarction was measured by TTC staining. The pathological changes of brain tissue were observed by HE staining. The levels of interleukin-1β （IL-1β），tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD），glutathione （GSH） in serum and the content of reduced coenzyme II （NADPH） in brain tissue were detected. The expression levels of nicotinamide phosphoribosyl transferase （NAMPT） and poly ADP ribose polymerase 1 （PARP1） in brain tissue were detected by Western Blot. Results Compared with the sham operation group，the neurological deficit score of the model group was significantly increased （P＜0.001）. The area of cerebral infarction was significantly increased （P＜0.001） . The levels of serum IL-1β and TNF-α were significantly increased （P＜0.01， P＜0.001）， and the levels of SOD and GSH were significantly decreased （P＜0.001）. The protein expression of NAMPT in the ischemic brain tissue was significantly up-regulated （P＜0.001），and the protein expression of PARP1 was significantly down-regulated （P＜0.01）. Compared with the model group，the neurological deficit scores of the rats in each administration group were significantly decreased （P＜0.05，P＜0.001）；the area of cerebral infarction was significantly reduced in the medium- and high- dose groups of Danxi Granules and Nimodipine group was significantly reduced （P＜0.01，P＜0.001）. The levels of serum IL-1β and TNF-α in the medium-dose group and the Nimodipine group were significantly decreased （P＜0.01，P＜0.001），the levels of SOD and GSH were significantly increased （P＜0.05，P＜0.01，P＜0.001），and the NADPH content and protein expressions of NAMPT and PARP1 in the ischemic brain tissue were significantly up-regulated （P＜0.05， P＜0.01）. Conclusion Danxi Granules can reduce the area of cerebral infarction in rats with cerebral ischemia-reperfusion injury， improve the pathological damage of brain tissue，reduce the neurological deficit score，reduce the level of inflammatory factors， and enhance the antioxidant capacity. The mechanism may be related to the activation of NAMPT and PARP1， the maintenance of NAD+ level，thus affecting DNA repair，inflammatory response and other aspects.

R285.5

湖南省重点研发计划项目（2021SK2007）；湖南省自然科学基金项目（2023JJ601130，2022JJ80075）。