陕西医学杂志2025，Vol.54Issue(10)：1316-1323,8.DOI:10.3969/j.issn.1000-7377.2025.10.004
大黄酸调控炎症小体活化抑制急性脑出血大鼠小胶质细胞焦亡的机制研究
Mechanism of rhubarbic acid modulation of inflammatory vesicle activation to inhibit microglial cell pyroptosis in rats with acute cerebral hemorrhage
摘要
Abstract
Objective:To explore the inhibitory effect and mechanism of rhubarbic acid on microglial cell focal death in rats with acute cerebral hemorrhage.Methods:The internationally recognized rat model of intracerebral hem-orrhage(ICH)was induced by injection of type Ⅶ collagenase;based on the sequence of NLRP3 gene,NLRP3-silen-cing adenovirus was constructed to establish an NLRP3-silencing rat model of ICH;VX-765 was injected into the tail vein to establish a Caspase-1-inhibited rat model of ICH.Fifty SD rats were randomly divided into a sham-operated group(Sham group,n=5),a cerebral hemorrhage group(ICH group,n=5),a sham-operated+rhubarbic acid-treated group(Sham+Rhein group,n=5),a cerebral hemorrhage+rhubarbic acid-treated group(ICH+Rhein group,n=5)a sham-operated+rhubarbic acid+shNLRP3-silenced group(Sham+Rhein+shNLRP3 group,n=5),cerebral hemor-rhage+rhubarbic acid+NLRP3 silencing group(ICH+Rhein+shNLRP3 group,n=5),sham-operated+rhubarbic acid+adenovirus-negative control group(Sham+Rhein+Ad-NC group,n=5),cerebral hemorrhage+rhubarbic acid+adenovirus-negative control group(ICH+Rhein+Ad-NC group,n=5),cerebral hemorrhage+Caspase-1 inhibitor group(ICH+Caspase-1 inhibitor group,n=5),and cerebral hemorrhage+Rhein+Caspase-1 inhibitor group(ICH+Rhein+Caspase-1 inhibitor group,n=5);After the 7th day of rhubarbic acid treatment,the levels of IL-1β,IL-18,TNF-α,IL-6,and iNOS were detected by ELISA,the inflammation level of brain tissue was detected by HE,and the expression of NLRP3,ASC,Caspase-1,and GSDMD were detected by Western blot and RT-qPCR.Results:① Medium-dose(Adv-M:5 × 109 pfu/pupil)and high-dose(Adv-H:1 × 1010 pfu/pupil)adenoviruses significantly re-duced the expression of NLRP3,and there was no statistically significant difference between them(P＞0.05);②Me-dium-dose(MDR,1.73 mg/kg)was the optimal dose for rhubarbic acid treatment;③The levels of inflammatory fac-tors(IL-1β,IL-18,TNF-α,IL-6,iNOS)and inflammation were significantly higher in the ICH group compared with the Sham group(all P＜0.05);the levels of inflammation in rats in the ICH+Rhein group were significantly lower in the ICH group compared with the ICH group(P＜0.05);the levels of inflammatory factors in rats in the ICH+Rhein group were significantly lower in the ICH+Rhein+shNLRP3 group and ICH+Rhein+Caspase-1 inhibitor group significantly made the level of inflammatory factors lower(all P＜0.05);④The levels of NLRP3,ASC,Caspase-1,and GSDMD were significantly higher in the ICH group compared with the Sham group(all P＜0.05);the levels of NLRP3,ASC,Caspase-1,and GSDMD were decreased in the brain tissues of the rats in the ICH+Rhein group compared with the ICH group(all P＜0.05),and the ICH+Rhein+shNLRP3 group as well as ICH+Rhein+Caspase-1 inhibitor group signif-icantly reduced the levels of NLRP3,ASC,Caspase-1,and GSDMD in the middle(all P＜0.05).Conclusion:Rhubarbic acid can inhibit microglial cell pyroptosis after ICH by regulating the activation of NLRP3 inflammatory vesicles,thereby reduc-ing the release of inflammatory factors and attenuating the level of inflammation in brain tissues,thus exerting the effects of inhibiting inflammatory responses and attenuating the secondary damage in brain tissues.关键词
大黄酸/脑出血/NLRP3炎症小体/小胶质细胞/细胞焦亡/机制Key words
Rhubarbic acid/Intracerebral hemorrhage/NLRP3 inflammatory vesicles/Microglia/Cellular py-roptosis/Mechanism分类
医药卫生引用本文复制引用
陈臣,李倩,刘涛,阿达来提·艾麦提..大黄酸调控炎症小体活化抑制急性脑出血大鼠小胶质细胞焦亡的机制研究[J].陕西医学杂志,2025,54(10):1316-1323,8.基金项目
新疆维吾尔自治区自然科学基金杰出青年科学基金资助项目(2022D01E79) （2022D01E79）
