中药新药与临床药理2025，Vol.36Issue(4)：499-505,7.DOI:10.19378/j.issn.1003-9783.2025.04.002
丹膝颗粒对脑缺血再灌注损伤大鼠的保护作用及机制
Study on the Protective Effect and Mechanism of Danxi Granules on Cerebral Ischemia-Reperfusion Injury in Rats
摘要
Abstract
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.关键词
丹膝颗粒/缺血性脑卒中/脑缺血再灌注损伤/多聚ADP核糖聚合酶1/烟酰胺磷酸核糖基转移酶/抗炎/抗氧化/大鼠Key words
Danxi Granules/ischemic stroke/cerebral ischemia-reperfusion injury/PARP1/NAMPT/anti-inflammatory/antioxidant/rats分类
医药卫生引用本文复制引用
龙慧玲,陶新如,冯小龙,李鹏辉,蔡媛,彭艳梅..丹膝颗粒对脑缺血再灌注损伤大鼠的保护作用及机制[J].中药新药与临床药理,2025,36(4):499-505,7.基金项目
湖南省重点研发计划项目(2021SK2007) （2021SK2007）
湖南省自然科学基金项目(2023JJ601130,2022JJ80075). （2023JJ601130,2022JJ80075）
