摘要
目的探究化痰祛瘀方调节消皮素D(GSDMD)/黑色素瘤缺乏因子2(AIM2)信号通路对痰瘀互结型缺血性脑卒中神经细胞焦亡的影响。方法大鼠以高脂饲料建立痰瘀互结模型成功后,以线栓法建立大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型,后随机分为空白组,假手术组,尼莫地平组,化痰祛瘀方低、中、高剂量组(0.66、1.33、2.66 g/kg)。MCAO造模成功大鼠术后24 h和72 h进行神经功能缺损评分;免疫组织化学检测皮质GSDMD/AIM2蛋白阳性表达;酶联免疫吸附试验(ELISA)检测大鼠血清高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,检测大鼠血清白细胞介素(IL)-1β、IL-18含量;Western blot检测焦亡相关蛋白GSDMD、Caspase-1及AIM2表达。结果与假手术组比较,尼莫地平组及化痰祛瘀方低、中剂量组大鼠神经功能缺损评分降低(P<0.05),中剂量组显著降低(P<0.01);与模型组比较,尼莫地平组及化痰祛瘀方低、中、高剂量组大鼠血清HDL-C、LDL-C、IL-1β、IL-18含量及GSDMD、Caspase-1、AIM2蛋白表达均降低(P<0.05),大鼠血清HDL-C、LDL-C、IL-1β、IL-18含量在化痰祛瘀方中剂量组显著降低(P<0.01)。结论化痰祛瘀方对痰瘀互结型缺血性脑卒中大鼠具有改善作用,通过下调GSDMD/AIM2通路减轻大鼠神经细胞焦亡。
Objective To explore the effect of Huatan Quyu Decoction(化痰祛瘀方)on regulating GSDMD/AIM2 signaling pathway on neuronal pyroptosis in phlegm stasis ischemic stroke.Methods After successfully establishing a phlegm blood stasis model in rats with high-fat diet,a middle cerebral artery occlusion(MCAO)model was established using the suture method.The rats were then randomly divided into blank group,sham operation group,Nifedipine group,and low,medium,and high dose groups of Huatan Quyu Decoction(0.66,1.33,2.66 g/kg).MCAO modeling was successful,and neurological function deficit scores were obtained at 24 and 72 hours after surgery in rats;Immunohistochemical detection of positive expression of GSDMD/AIM2 protein in the cortex;Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)in rat serum,as well as the levels of interleukin-1βand IL-18 in rat serum;Western blot was used to detect the expression of apoptosis related proteins GSDMD,Caspase-1,and AIM2.Results Compared with the sham surgery group,the neurological deficit score of rats decreased significantly(P<0.05),and the medium dose group showed a significant decrease(P<0.01);Compared with the model group,the levels of serum HDL-C,LDL-C,IL-1β,IL-18,GSDMD,Caspase-1,and AIM2 protein expression were significantly reduced in the low,medium,and high groups of rats treated with Nimodipine and Huatan Quyu Decoction(P<0.05).The levels of serum HDL-C,LDL-C,IL-1β,and IL-18 were significantly reduced in the medium dose group of Huatan Quyu Decoction(P<0.01).Conclusion Huatan Quyu Decoction has improving effect on ischemic stroke rats with phlegm blood stasis syndrome,by downregulating the GSDMD/AIM2 pathway to alleviate neuronal pyroptosis in rats.
作者
阴俊
闫咏梅
杨一帆
胡周圆
云烨栋
吕友慧
YIN Jun;YAN Yongmei;YANG Yifan;HU Zhouyuan;YUN Yedong;LYU Youhui(Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China;Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China;Ankang Hospital of Traditional Chinese Medicine,Ankang 725000,Shaanxi,China)
出处
《辽宁中医药大学学报》
2025年第11期25-30,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家中医药管理局岐黄学者支持项目(国中医药人教函〔2022〕6号)
陕西省中医脑病学重点实验室项目(KF202314)。
