Objective To explore the effect of Xuebijing injection on microglial pyroptosis after cerebral hemorrhage. Methods (1) Cell experiment. BV2 microglia of mice were treated by Xuebijing injection in 12.5 mL/L, 25 mL/L, and 50 mL/L for 24 hours, and the effect of Xuebijing injection on cell survival rate was observed. BV2 microglia were randomly assigned to control group, model group, or Xuebijing group. The microglial pyroptosis model after cerebral hemorrhage in the model group and the Xuebijing group was established by employing oxygenated hemoglobin and Nigericin costimulation method, therein the Xuebijing group received 50 mL/L Xuebijing injection for pre⁃treatment before 1 hour of modeling, whereas the control and model groups received complete medium for treatment. After 24 hours of modeling, the morphological changes of cells were observed via light microscope. Expressions of pyroptosis⁃related molecules NLR family pyrin domain containing 3 (NLRP3), apoptosis⁃associated speck⁃like protein containing CARD (ASC), Caspase⁃1 mRNAs were detected by using the reverse transcription PCR in various groups. Levels of tumor necrosis factor (TNF)⁃α, interleukin (IL)⁃18, IL⁃1β in cell supernatant were detected by employing the ELISA. (2) Animal experiment. A total of 54 rats were randomly assigned to control group, cerebral hemorrhage group, or Xuebijing group, with 18 rats in each group. The cerebral hemorrhage model of the cerebral hemorrhage group and the Xuebijing group was established by employing collagenase solution injection method, therein the Xuebijing group received pre⁃treatment of Xuebijing injection in 10 mL/kg before 1 hour of modeling, whereas the control group and the cerebral hemorrhage group received treatment by equivalent volume of normal saline. After 24 hours of modeling, the modified Garcia score was used to evaluate degree of nerve function impairment in rats, and the brain stem⁃to⁃wet mass ratio method was used to evaluate cerebral edema. The immunohistochemistry and immunofluorescence staining were used to observe the expressions of NLRP3 and gasdermin D protein terminal⁃N (GSDMD⁃N) in brain tissue of rats. The Western blot was employed to detect protein expressions of NLRP3 and Caspase⁃1 in brain tissues of rats. Results (1) Cell experiment. There was no significant effect of different concentrations Xuebijing injection on the survival rate of BV2 microglia; therefore, clinical commonly used high⁃concentration Xuebijing injection in 50 mL/L was selected for performing intervention in the follow⁃up experiment. Compared with the control group, the model group exhibited increased lactate dehydrogenase activity; moreover, compared with the model group, the Xuebijing group yielded decreased lactate dehydrogenase activity (P<0.05). Compared with the control group, the model group exhibited elevated mRNA expressions of NLRP3, ASC, and Caspase⁃1, as well as elevated levels of TNF⁃α, IL⁃18, IL⁃1β; furthermore, compared with the model group, the Xuebijing group yielded decreased NLRP3, ASC, and Caspase⁃1 mRNA expressions, and TNF⁃α, IL⁃18, IL⁃1β levels (P<0.05). (2) Animal experiment. Compared with the control group, rats of the cerebral hemorrhage group obtained elevated water content in brain tissues, a decreased modified Garcia score, increased NLRP3 positive staining in brain tissues, increased co⁃localization fluorescence intensity between GSDMD⁃N and microglia in brain tissues, and elevated protein expressions of NLRP3 and Caspase⁃1. Compared with the cerebral hemorrhage group, the Xuebijing group interpreted decreased water content in brain tissues, an elevated modified Garcia score, decreased NLRP3 positive staining in brain tissues, decreased co⁃localization fluorescence intensity between GSDMD⁃N and microglia in brian tissues, and decreased protein expressions of NLRP3 and Caspase⁃1 (P<0.05). Conclusion Xuebijing injection can relieve microglial pyroptosis and nerve function impairment after cerebral hemorrhage in mice/rats, and its mechanism may be related to reduce the release of proinflammatory factors, and alleviate neuroinflammatory reactions after cerebral hemorrhage through microglial pyroptosis mediated by regulation of NLRP3/Caspase⁃1/GSDMD⁃N signaling pathway. 

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