犀角地黄汤加减方抑制焦亡相关蛋白减轻脓毒症致急性肺损伤机制研究  

Study on the Mechanism of Xijiao Dihuang Decoction Inhibiting Pyroptosis-related Proteins in Alleviating Acute Lung Injury Induced by Sepsis

作　　者：赵媛 刘登 施荣[1] Zhao Yuan;Liu Deng;Shi Rong(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 201204,China)

机构地区：[1]上海中医药大学附属曙光医院,上海201204 [2]上海中医药大学,上海201204

出　　处：《中国中医急症》2024年第3期405-408,414,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82174121);上海中医药大学附属曙光医院“中西医结合研究专项”(SGZXY-202207)。

摘　　要：目的探讨犀角地黄汤加减方通过抑制焦亡相关蛋白减轻脓毒症小鼠肺损伤的机制。方法将小鼠分为假手术组、模型组、抑制剂组、中药低剂量组和中药高剂量组。采用盲肠结扎穿孔术制备脓毒症小鼠模型,于造模后12 h处死小鼠,双抗体夹心酶联免疫吸附法测定小鼠血清白细胞介素-1β(IL-1β)、白细胞介素18(IL-18)水平,留取完整左肺组织行病理切片,评估肺损伤情况,留取右肺组织提取RNA和蛋白,RT-PCR、Western blotting定量检测肺组织中NF-κB、NLRP3和Caspase-1、GSDMD的表达。结果与模型组比较,抑制剂组小鼠血清中IL-1β、IL-18水平显著降低(P<0.01),肺组织中Caspase-1、GSDMD基因和蛋白的表达下调,差异均具有显著统计学意义(P<0.01);与模型组相比,中药组小鼠血清中IL-1β、IL-18水平显著降低(P<0.01),肺损伤减轻,肺组织中NF-κB、NLRP3和Caspase-1、GSDMD基因和蛋白的表达下调,差异均具有统计学意义(P<0.01),且中药高、低剂量组间的差异有统计学意义(P<0.01)。结论犀角地黄汤加减方能够通过抑制焦亡相关通路蛋白来减轻脓毒症肺损伤,且与药物浓度相关。Objective:To explore the mechanism of Xijiao Dihuang Decoction in alleviating lung injury in sep⁃tic mice by inhibiting pyroptosis-related proteins.Methods:The mice were divided into sham operation group,model group,inhibitor group,low dose Xijiao Dihuang Decoction group and high dose Xijiao Dihuang Decoction group.The septic mouse model was constructed by cecal ligation and puncture and the modeled mice were killed at 12 h.The levels of serum IL-1βand IL-18 were determined by double antibody sandwich enzyme-linked im⁃munosorbent assay(ELISA).The intact left lung tissue was taken for pathological section to evaluate the lung inju⁃ry.RNA and protein were extracted from the right lung tissue,and the expressions of NF-κB,NLRP3,Caspase-1 and GSDMD in the lung tissue were detected by RT-PCR and Western blotting.Results:Compared with the mod⁃el group,the levels of serum IL-1βand IL-18 in the inhibitor group were significantly lower than those in the model group,and the expression of Caspase-1 and GSDMD genes and proteins in lung tissue were down-regulat⁃ed.Compared with the model group,the levels of IL-1βand IL-18 in serum of mice in Xijiao Dihuang Decoction group decreased significantly,alleviated lung injury,and down-regulated the expression of NF-κB,NLRP3,Cas⁃pase-1,GSDMD gene and protein in lung tissue,and there were significant differences among different dosage groups(P<0.01).Conclusion:Xijiao Dihuang Decoction can reduce septic lung injury by inhibiting pyroptosisrelated pathway proteins,and it is related to drug concentration.

关 键 词：脓毒症 肺损伤 犀角地黄汤加减方 焦亡 小鼠 

分 类 号：R285.5[医药卫生—中药学]