文献类型：期刊文献

中文题名：当归黄芪超滤物通过调控NLRP3/caspase-1/GSDMD焦亡途径改善放射性大鼠肺纤维化

英文题名：Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract improves radiation-induced pulmonary fibrosis in rats by regulating NLRP3/caspase-1/GSDMD pyroptosis pathway

作者：任春贞[1,2,3];袁剑芳[1,2];王春玲[1,2];支晓东[1,2,3];张启立[4];陈其林[1,2];吕欣芳[1,2,3];高翔[1,2,3];吴雪[1,2];赵信科[1,2,3];李应东[1,2,3]

第一作者：任春贞

机构：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃省中医药防治慢性病重点实验室,甘肃兰州730000;[3]甘肃中医药大学附属医院,甘肃兰州730000;[4]甘肃中医药大学药学院,甘肃兰州730000

第一机构：甘肃中医药大学中西医结合学院

年份：2024

卷号：40

期号：11

起止页码：2124

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：CSTPCD;;Scopus;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金资助项目(No 82260869,82360926,82374279);甘肃教育揭榜挂帅项目(No 2021jyjbgs-03);甘肃省中医药防治重大疾病专项(No GZKZD-2018-02);甘肃省科技重大专项(No 20ZD7FA002);甘肃省陇原青年创新创业人才项目;甘肃省青年科技基金资助项目(No 23JRRA1217);甘肃省优秀博士生项目(No 24JRRA569)。

语种：中文

中文关键词：当归黄芪超滤物;放射性肺纤维化;焦亡;炎症;NLRP3/caspase-1/GSDMD途径

外文关键词：Radix Angelica sinensis and Radix Astragalus ultrafiltration extract;radiation-induced pulmonary fibrosis;pyroptosis;inflammation;NLRP3/caspase-1/GSDMD pathway

摘要：目的探讨NLRP3/caspase-1/GSDMD信号通路介导的焦亡在放射性肺纤维化中的作用机制及当归黄芪超滤物(Radix Angelica sinensis and Radix Astragalus ultrafiltration extract,RAS-RA)的干预作用。方法随机将50只Wistar大鼠分为5组,每组10只。除空白对照组不予辐射外,其余各组大鼠均经麻醉后接受40 Gy X射线单次局部胸部照射1次,建立放射性肺纤维化大鼠模型。辐射后,RAS-RA各干预组大鼠以0.12、0.24、0.48 g·kg^(-1)剂量分别灌胃,每天1次,连续给药30 d。连续给药30 d后,观察大鼠平均体质量和肺脏指数;水解法测定肺组织中羟脯氨酸的含量;ELISA检测肺组织及血清IL-18和IL-1β的含量;HE及Masson染色观察肺组织病理变化;透射电镜观察肺组织超微结构变化;Western blot检测肺组织NLRP3/caspase-1/GSDMD焦亡通路相关蛋白及纤维化蛋白表达水平。结果与空白组比较,模型组大鼠肺组织中羟脯氨酸IL-18、IL-1β含量以及血清中IL-18、IL-1β的水平明显升高(P<0.01);HE及Masson显示有炎性细胞聚集及胶原纤维沉积;透射电镜显示受损线粒体数量增多、排列紊乱、形态不规则,基质变浅,外膜破裂,嵴大多断裂、变短,轻微扩张,个别线粒体基质电子密度增高,板层小体板层结构轻度稀疏,部分排列紊乱,细胞器模糊不清,出现焦亡特征性改变;Western blot检测显示caspase-1、GSDMD、NLRP3、CoL-Ⅰ、α-SMA、CoL-Ⅲ蛋白表达升高(P<0.05)。与模型组比较,RAS-RA干预组明显改善大鼠平均体质量及肺脏指数,IL-18、IL-1β炎症因子水平降低(P<0.01);线粒体结构好转;纤维化程度减轻;肺组织中caspase-1、GSDMD、NLRP3、COL-Ⅰ、COL-Ⅲ、α-SMA蛋白表达下降(P<0.01)。结论RAS-RA对放射性肺纤维化具有抑制作用,其机制可能是通过调控NLRP3/caspase-1/GSDMD信号通路抑制焦亡发挥抗肺纤维化的作用。
Aim To investigate the mechanism of pyroptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fibrosis.Methods Fifty Wistar rats were randomly divided into five groups,with ten rats in each group.Except for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-induced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg^(-1) once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of continuous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1βin serum were detected by ELISA.Lung tissue pathological changes were observed by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission electron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detected by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1βin serum significantly increased in the model group(P<0.01).HE and Masson staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron microscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲproteins(P<0.01).Compared with the model group,the RAS-RA intervention group showed significant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1βinflammatory factors(P<0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,andα-SMA proteins in lung tissue(P<0.01).Conclusion RAS-RA has an inhibitory effect on radiation-induced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regulation of the NLRP3/caspase-1/GSDMD signaling pathway.